Patent Publication Number: US-2022236286-A1

Title: Methods and compositions for diagnosis and prognosis of renal injury and renal failure

Description:
This application claims the benefit of U.S. Provisional Application No. 62/066,310 filed Oct. 20, 2014; and of U.S. Provisional Application No. 62/066,313 filed Oct. 20, 2014; and of U.S. Provisional Application No. 62/066,316 filed Oct. 20, 2014; each of which is hereby incorporated in its entirety including all tables, figures, and claims. 
    
    
     BACKGROUND OF THE INVENTION 
     The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention. 
     The kidney is responsible for water and solute excretion from the body. Its functions include maintenance of acid-base balance, regulation of electrolyte concentrations, control of blood volume, and regulation of blood pressure. As such, loss of kidney function through injury and/or disease results in substantial morbidity and mortality. A detailed discussion of renal injuries is provided in Harrison&#39;s Principles of Internal Medicine, 17 th  Ed., McGraw Hill, New York, pages 1741-1830, which are hereby incorporated by reference in their entirety. Renal disease and/or injury may be acute or chronic. Acute and chronic kidney disease are described as follows (from Current Medical Diagnosis &amp; Treatment 2008, 47 th  Ed, McGraw Hill, New York, pages 785-815, which are hereby incorporated by reference in their entirety): “Acute renal failure is worsening of renal function over hours to days, resulting in the retention of nitrogenous wastes (such as urea nitrogen) and creatinine in the blood. Retention of these substances is called azotemia. Chronic renal failure (chronic kidney disease) results from an abnormal loss of renal function over months to years”. 
     Acute renal failure (ARF, also known as acute kidney injury, or AKI) is an abrupt (typically detected within about 48 hours to 1 week) reduction in glomerular filtration. This loss of filtration capacity results in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products that are normally excreted by the kidney, a reduction in urine output, or both. It is reported that ARF complicates about 5% of hospital admissions, 4-15% of cardiopulmonary bypass surgeries, and up to 30% of intensive care admissions. ARF may be categorized as prerenal, intrinsic renal, or postrenal in causation. Intrinsic renal disease can be further divided into glomerular, tubular, interstitial, and vascular abnormalities. Major causes of ARF are described in the following table, which is adapted from the Merck Manual, 17 th  ed., Chapter 222, and which is hereby incorporated by reference in their entirety: 
     
       
         
           
               
               
             
               
                   
               
               
                 Type 
                 Risk Factors 
               
               
                   
               
             
            
               
                 Prerenal 
                   
               
               
                 ECF volume depletion 
                 Excessive diuresis, hemorrhage, GI losses, loss of 
               
               
                   
                 intravascular fluid into the extravascular space (due to 
               
               
                   
                 ascites, peritonitis, pancreatitis, or burns), loss of skin 
               
               
                   
                 and mucus membranes, renal salt- and water-wasting states 
               
               
                 Low cardiac output 
                 Cardiomyopathy, MI, cardiac tamponade, pulmonary embolism, 
               
               
                   
                 pulmonary hypertension, positive-pressure mechanical ventilation 
               
               
                 Low systemic vascular 
                 Septic shock, liver failure, antihypertensive drugs 
               
               
                 resistance 
                   
               
               
                 Increased renal vascular 
                 NSAIDs, cyclosporines, tacrolimus, hypercalcemia, 
               
               
                 resistance 
                 anaphylaxis, anesthetics, renal artery obstruction, renal 
               
               
                   
                 vein thrombosis, sepsis, hepatorenal syndrome 
               
               
                 Decreased efferent 
                 ACE inhibitors or angiotensin II receptor blockers 
               
               
                 arteriolar tone (leading to 
                   
               
               
                 decreased GFR from 
                   
               
               
                 reduced glomerular 
                   
               
               
                 transcapillary pressure, 
                   
               
               
                 especially in patients with 
                   
               
               
                 bilateral renal artery 
                   
               
               
                 stenosis) 
                   
               
               
                 Intrinsic Renal 
                   
               
               
                 Acute tubular injury 
                 Ischemia (prolonged or severe prerenal state): surgery, 
               
               
                   
                 hemorrhage, arterial or venous obstruction; Toxins: 
               
               
                   
                 NSAIDs, cyclosporines, tacrolimus, aminoglycosides, 
               
               
                   
                 foscarnet, ethylene glycol, hemoglobin, myoglobin, 
               
               
                   
                 ifosfamide, heavy metals, methotrexate, radiopaque 
               
               
                   
                 contrast agents, streptozotocin 
               
               
                 Acute glomerulonephritis 
                 ANCA-associated: Crescentic glomerulonephritis, 
               
               
                   
                 polyarteritis nodosa, Wegener&#39;s granulomatosis; Anti- 
               
               
                   
                 GBM glomerulonephritis: Goodpasture&#39;s syndrome; 
               
               
                   
                 Immune-complex: Lupus glomerulonephritis, 
               
               
                   
                 postinfectious glomerulonephritis, cryoglobulinemic 
               
               
                   
                 glomerulonephritis 
               
               
                 Acute tubulointerstitial 
                 Drug reaction (eg, β-lactams, NSAIDs, sulfonamides, 
               
               
                 nephritis 
                 ciprofloxacin, thiazide diuretics, furosemide, phenytoin, 
               
               
                   
                 allopurinol, pyelonephritis, papillary necrosis 
               
               
                 Acute vascular 
                 Vasculitis, malignant hypertension, thrombotic 
               
               
                 nephropathy 
                 microangiopathies, scleroderma, atheroembolism 
               
               
                 Infiltrative diseases 
                 Lymphoma, sarcoidosis, leukemia 
               
               
                 Postrenal 
                   
               
               
                 Tubular precipitation 
                 Uric acid (tumor lysis), sulfonamides, triamterene, 
               
               
                   
                 acyclovir, indinavir, methotrexate, ethylene glycol 
               
               
                   
                 ingestion, myeloma protein, myoglobin 
               
               
                 Ureteral obstruction 
                 Intrinsic: Calculi, clots, sloughed renal tissue, fungus 
               
               
                   
                 ball, edema, malignancy, congenital defects; Extrinsic: 
               
               
                   
                 Malignancy, retroperitoneal fibrosis, ureteral trauma 
               
               
                   
                 during surgery or high impact injury 
               
               
                 Bladder obstruction 
                 Mechanical: Benign prostatic hyperplasia, prostate 
               
               
                   
                 cancer, bladder cancer, urethral strictures, phimosis, 
               
               
                   
                 paraphimosis, urethral valves, obstructed indwelling 
               
               
                   
                 urinary catheter; Neurogenic: Anticholinergic drugs, 
               
               
                   
                 upper or lower motor neuron lesion 
               
               
                   
               
            
           
         
       
     
     In the case of ischemic ARF, the course of the disease may be divided into four phases. During an initiation phase, which lasts hours to days, reduced perfusion of the kidney is evolving into injury. Glomerular ultrafiltration reduces, the flow of filtrate is reduced due to debris within the tubules, and back leakage of filtrate through injured epithelium occurs. Renal injury can be mediated during this phase by reperfusion of the kidney. Initiation is followed by an extension phase which is characterized by continued ischemic injury and inflammation and may involve endothelial damage and vascular congestion. During the maintenance phase, lasting from 1 to 2 weeks, renal cell injury occurs, and glomerular filtration and urine output reaches a minimum. A recovery phase can follow in which the renal epithelium is repaired and GFR gradually recovers. Despite this, the survival rate of subjects with ARF may be as low as about 60%. 
     Acute kidney injury caused by radiocontrast agents (also called contrast media) and other nephrotoxins such as cyclosporine, antibiotics including aminoglycosides and anticancer drugs such as cisplatin manifests over a period of days to about a week. Contrast induced nephropathy (CIN, which is AKI caused by radiocontrast agents) is thought to be caused by intrarenal vasoconstriction (leading to ischemic injury) and from the generation of reactive oxygen species that are directly toxic to renal tubular epithelial cells. CIN classically presents as an acute (onset within 24-48 h) but reversible (peak 3-5 days, resolution within 1 week) rise in blood urea nitrogen and serum creatinine. 
     A commonly reported criteria for defining and detecting AKI is an abrupt (typically within about 2-7 days or within a period of hospitalization) elevation of serum creatinine. Although the use of serum creatinine elevation to define and detect AKI is well established, the magnitude of the serum creatinine elevation and the time over which it is measured to define AKI varies considerably among publications. Traditionally, relatively large increases in serum creatinine such as 100%, 200%, an increase of at least 100% to a value over 2 mg/dL and other definitions were used to define AKI. However, the recent trend has been towards using smaller serum creatinine rises to define AKI. The relationship between serum creatinine rise, AKI and the associated health risks are reviewed in Praught and Shlipak,  Curr Opin Nephrol Hypertens  14:265-270, 2005 and Chertow et al,  J Am Soc Nephrol  16: 3365-3370, 2005, which, with the references listed therein, are hereby incorporated by reference in their entirety. As described in these publications, acute worsening renal function (AKI) and increased risk of death and other detrimental outcomes are now known to be associated with very small increases in serum creatinine. These increases may be determined as a relative (percent) value or a nominal value. Relative increases in serum creatinine as small as 20% from the pre-injury value have been reported to indicate acutely worsening renal function (AKI) and increased health risk, but the more commonly reported value to define AKI and increased health risk is a relative increase of at least 25%. Nominal increases as small as 0.3 mg/dL, 0.2 mg/dL or even 0.1 mg/dL have been reported to indicate worsening renal function and increased risk of death. Various time periods for the serum creatinine to rise to these threshold values have been used to define AKI, for example, ranging from 2 days, 3 days, 7 days, or a variable period defined as the time the patient is in the hospital or intensive care unit. These studies indicate there is not a particular threshold serum creatinine rise (or time period for the rise) for worsening renal function or AKI, but rather a continuous increase in risk with increasing magnitude of serum creatinine rise. 
     One study (Lassnigg et all, J Am Soc Nephrol 15:1597-1605, 2004, hereby incorporated by reference in its entirety) investigated both increases and decreases in serum creatinine. Patients with a mild fall in serum creatinine of −0.1 to −0.3 mg/dL following heart surgery had the lowest mortality rate. Patients with a larger fall in serum creatinine (more than or equal to −0.4 mg/dL) or any increase in serum creatinine had a larger mortality rate. These findings caused the authors to conclude that even very subtle changes in renal function (as detected by small creatinine changes within 48 hours of surgery) seriously effect patient&#39;s outcomes. In an effort to reach consensus on a unified classification system for using serum creatinine to define AKI in clinical trials and in clinical practice, Bellomo et al., Crit Care. 8(4):R204-12, 2004, which is hereby incorporated by reference in its entirety, proposes the following classifications for stratifying AKI patients: 
     “Risk”: serum creatinine increased 1.5 fold from baseline OR urine production of &lt;0.5 ml/kg body weight/hr for 6 hours;
 
“Injury”: serum creatinine increased 2.0 fold from baseline OR urine production &lt;0.5 ml/kg/hr for 12 h;
 
“Failure”: serum creatinine increased 3.0 fold from baseline OR creatinine &gt;355 μmol/l (with a rise of &gt;44) or urine output below 0.3 ml/kg/hr for 24 h or anuria for at least 12 hours;
 
And included two clinical outcomes:
 
“Loss”: persistent need for renal replacement therapy for more than four weeks.
 
“ESRD”: end stage renal disease—the need for dialysis for more than 3 months.
 
These criteria are called the RIFLE criteria, which provide a useful clinical tool to classify renal status. As discussed in Kellum,  Crit. Care Med.  36: S141-45, 2008 and Ricci et al.,  Kidney Int.  73, 538-546, 2008, each hereby incorporated by reference in its entirety, the RIFLE criteria provide a uniform definition of AKI which has been validated in numerous studies.
 
     More recently, Mehta et al., Crit. Care 11:R31 (doi:10.1186.cc5713), 2007, hereby incorporated by reference in its entirety, proposes the following similar classifications for stratifying AKI patients, which have been modified from RIFLE: 
     “Stage I”: increase in serum creatinine of more than or equal to 0.3 mg/dL (≥26.4 μmol/L) or increase to more than or equal to 150% (1.5-fold) from baseline OR urine output less than 0.5 mL/kg per hour for more than 6 hours;
 
“Stage II”: increase in serum creatinine to more than 200% (&gt;2-fold) from baseline OR urine output less than 0.5 mL/kg per hour for more than 12 hours;
 
“Stage III”: increase in serum creatinine to more than 300% (&gt;3-fold) from baseline OR serum creatinine ≥354 μmol/L accompanied by an acute increase of at least 44 μmol/L OR urine output less than 0.3 mL/kg per hour for 24 hours or anuria for 12 hours.
 
     The CIN Consensus Working Panel (McCollough et al, Rev Cardiovasc Med. 2006; 7(4):177-197, hereby incorporated by reference in its entirety) uses a serum creatinine rise of 25% to define Contrast induced nephropathy (which is a type of AKI). Although various groups propose slightly different criteria for using serum creatinine to detect AKI, the consensus is that small changes in serum creatinine, such as 0.3 mg/dL or 25%, are sufficient to detect AKI (worsening renal function) and that the magnitude of the serum creatinine change is an indicator of the severity of the AKI and mortality risk. 
     Although serial measurement of serum creatinine over a period of days is an accepted method of detecting and diagnosing AKI and is considered one of the most important tools to evaluate AKI patients, serum creatinine is generally regarded to have several limitations in the diagnosis, assessment and monitoring of AKI patients. The time period for serum creatinine to rise to values (e.g., a 0.3 mg/dL or 25% rise) considered diagnostic for AKI can be 48 hours or longer depending on the definition used. Since cellular injury in AKI can occur over a period of hours, serum creatinine elevations detected at 48 hours or longer can be a late indicator of injury, and relying on serum creatinine can thus delay diagnosis of AKI. Furthermore, serum creatinine is not a good indicator of the exact kidney status and treatment needs during the most acute phases of AKI when kidney function is changing rapidly. Some patients with AKI will recover fully, some will need dialysis (either short term or long term) and some will have other detrimental outcomes including death, major adverse cardiac events and chronic kidney disease. Because serum creatinine is a marker of filtration rate, it does not differentiate between the causes of AKI (pre-renal, intrinsic renal, post-renal obstruction, atheroembolic, etc) or the category or location of injury in intrinsic renal disease (for example, tubular, glomerular or interstitial in origin). Urine output is similarly limited, Knowing these things can be of vital importance in managing and treating patients with AKI. 
     These limitations underscore the need for better methods to detect and assess AKI, particularly in the early and subclinical stages, but also in later stages when recovery and repair of the kidney can occur. Furthermore, there is a need to better identify patients who are at risk of having an AKI. 
     BRIEF SUMMARY OF THE INVENTION 
     It is an object of the invention to provide methods and compositions for evaluating renal function in a subject. As described herein, measurement of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and Tyrosine-protein kinase receptor UFO (collectively referred to herein as “kidney injury markers, and individually as a “kidney injury marker”) can be used for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury). 
     These kidney injury markers may be used, individually or in panels comprising a plurality of kidney injury markers, for risk stratification (that is, to identify subjects at risk for a future injury to renal function, for future progression to reduced renal function, for future progression to ARF, for future improvement in renal function, etc.); for diagnosis of existing disease (that is, to identify subjects who have suffered an injury to renal function, who have progressed to reduced renal function, who have progressed to ARF, etc.); for monitoring for deterioration or improvement of renal function; and for predicting a future medical outcome, such as improved or worsening renal function, a decreased or increased mortality risk, a decreased or increased risk that a subject will require renal replacement therapy (i.e., hemodialysis, peritoneal dialysis, hemofiltration, and/or renal transplantation, a decreased or increased risk that a subject will recover from an injury to renal function, a decreased or increased risk that a subject will recover from ARF, a decreased or increased risk that a subject will progress to end stage renal disease, a decreased or increased risk that a subject will progress to chronic renal failure, a decreased or increased risk that a subject will suffer rejection of a transplanted kidney, etc. 
     In a first aspect, the present invention relates to methods for evaluating renal status in a subject. These methods comprise performing an assay method that is configured to detect one or more kidney injury markers of the present invention in a body fluid sample obtained from the subject. The assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are then correlated to the renal status of the subject. This correlation to renal status may include correlating the assay result(s) to one or more of risk stratification, diagnosis, prognosis, staging, classifying and monitoring of the subject as described herein. Thus, the present invention utilizes one or more kidney injury markers of the present invention for the evaluation of renal injury. 
     In certain embodiments, the methods for evaluating renal status described herein are methods for risk stratification of the subject; that is, assigning a likelihood of one or more future changes in renal status to the subject. In these embodiments, the assay result(s) is/are correlated to one or more such future changes. The following are preferred risk stratification embodiments. 
     In preferred risk stratification embodiments, these methods comprise determining a subject&#39;s risk for a future injury to renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a likelihood of such a future injury to renal function. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of suffering a future injury to renal function is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of suffering a future injury to renal function is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold. 
     In other preferred risk stratification embodiments, these methods comprise determining a subject&#39;s risk for future reduced renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a likelihood of such reduced renal function. For example, the measured concentrations may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of suffering a future reduced renal function is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of future reduced renal function is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold. 
     In still other preferred risk stratification embodiments, these methods comprise determining a subject&#39;s likelihood for a future improvement in renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a likelihood of such a future improvement in renal function. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of a future improvement in renal function is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold. For a “negative going” kidney injury marker, an increased likelihood of a future improvement in renal function is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. 
     In yet other preferred risk stratification embodiments, these methods comprise determining a subject&#39;s risk for progression to ARF, and the result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a likelihood of such progression to ARF. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of progression to ARF is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of progression to ARF is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold. 
     And in other preferred risk stratification embodiments, these methods comprise determining a subject&#39;s outcome risk, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a likelihood of the occurrence of a clinical outcome related to a renal injury suffered by the subject. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of one or more of: acute kidney injury, progression to a worsening stage of AKI, mortality, a requirement for renal replacement therapy, a requirement for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, progression to chronic kidney disease, etc., is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of one or more of: acute kidney injury, progression to a worsening stage of AKI, mortality, a requirement for renal replacement therapy, a requirement for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, progression to chronic kidney disease, etc., is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold. 
     In such risk stratification embodiments, preferably the likelihood or risk assigned is that an event of interest is more or less likely to occur within 180 days of the time at which the body fluid sample is obtained from the subject. In particularly preferred embodiments, the likelihood or risk assigned relates to an event of interest occurring within a shorter time period such as 18 months, 120 days, 90 days, 60 days, 45 days, 30 days, 21 days, 14 days, 7 days, 5 days, 96 hours, 72 hours, 48 hours, 36 hours, 24 hours, 12 hours, or less. A risk at 0 hours of the time at which the body fluid sample is obtained from the subject is equivalent to diagnosis of a current condition. 
     In preferred risk stratification embodiments, the subject is selected for risk stratification based on the pre-existence in the subject of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF. For example, a subject undergoing or having undergone major vascular surgery, coronary artery bypass, or other cardiac surgery; a subject having pre-existing congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, glomerular filtration below the normal range, cirrhosis, serum creatinine above the normal range, or sepsis; or a subject exposed to NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin are all preferred subjects for monitoring risks according to the methods described herein. This list is not meant to be limiting. By “pre-existence” in this context is meant that the risk factor exists at the time the body fluid sample is obtained from the subject. In particularly preferred embodiments, a subject is chosen for risk stratification based on an existing diagnosis of injury to renal function, reduced renal function, or ARF. 
     In other embodiments, the methods for evaluating renal status described herein are methods for diagnosing a renal injury in the subject; that is, assessing whether or not a subject has suffered from an injury to renal function, reduced renal function, or ARF. In these embodiments, the assay result(s) is/are correlated to the occurrence or nonoccurrence of a change in renal status. The following are preferred diagnostic embodiments. 
     In preferred diagnostic embodiments, these methods comprise diagnosing the occurrence or nonoccurrence of an injury to renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of such an injury. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury to renal function is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury to renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury to renal function is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury to renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold). 
     In other preferred diagnostic embodiments, these methods comprise diagnosing the occurrence or nonoccurrence of reduced renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of an injury causing reduced renal function. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury causing reduced renal function is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury causing reduced renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury causing reduced renal function is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury causing reduced renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold). 
     In yet other preferred diagnostic embodiments, these methods comprise diagnosing the occurrence or nonoccurrence of ARF, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of an injury causing ARF. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of ARF is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of ARF may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of ARF is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of ARF may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold). 
     In still other preferred diagnostic embodiments, these methods comprise diagnosing a subject as being in need of renal replacement therapy, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a need for renal replacement therapy. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury creating a need for renal replacement therapy is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal replacement therapy may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury creating a need for renal replacement therapy is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal replacement therapy may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold). 
     In still other preferred diagnostic embodiments, these methods comprise diagnosing a subject as being in need of renal transplantation, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a need for renal transplantation. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury creating a need for renal transplantation is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal transplantation may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury creating a need for renal transplantation is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal transplantation may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold). 
     In still other embodiments, the methods for evaluating renal status described herein are methods for monitoring a renal injury in the subject; that is, assessing whether or not renal function is improving or worsening in a subject who has suffered from an injury to renal function, reduced renal function, or ARF. In these embodiments, the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of a change in renal status. The following are preferred monitoring embodiments. 
     In preferred monitoring embodiments, these methods comprise monitoring renal status in a subject suffering from an injury to renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject. 
     In other preferred monitoring embodiments, these methods comprise monitoring renal status in a subject suffering from reduced renal function, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject. 
     In yet other preferred monitoring embodiments, these methods comprise monitoring renal status in a subject suffering from acute renal failure, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject. 
     In other additional preferred monitoring embodiments, these methods comprise monitoring renal status in a subject at risk of an injury to renal function due to the pre-existence of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject. 
     In yet other preferred monitoring embodiments, these methods comprise monitoring renal status in a subject having, or at risk of, an injury to renal function for future persistence of acute kidney injury. “Future persistence” as used herein refers to an existing acute renal injury that will continue for a period selected from the group consisting of 21 days, 14 days, 7 days, 5 days, 96 hours, 72 hours, 48 hours, 36 hours, 24 hours, and 12 hours. In certain embodiments the subject has an acute kidney injury at the time the sample is obtained. This is not meant to imply that the subject must have an acute kidney injury at the time the sample is obtained, but rather that the subject, upon onset of an acute kidney injury, suffers from an acute kidney injury that will persist. In various embodiments, the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the future persistence of the acute kidney injury in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a future persistence of acute kidney injury may be assigned to the subject; alternatively, when the measured concentration is below the threshold, a future improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a future persistence of acute kidney injury may be assigned to the subject; alternatively, when the measured concentration is above the threshold, a future improvement of renal function may be assigned to the subject. 
     In still other embodiments, the methods for evaluating renal status described herein are methods for classifying a renal injury in the subject; that is, determining whether a renal injury in a subject is prerenal, intrinsic renal, or postrenal; and/or further subdividing these classes into subclasses such as acute tubular injury, acute glomerulonephritis acute tubulointerstitial nephritis, acute vascular nephropathy, or infiltrative disease; and/or assigning a likelihood that a subject will progress to a particular RIFLE stage. In these embodiments, the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to a particular class and/or subclass. The following are preferred classification embodiments. 
     In preferred classification embodiments, these methods comprise determining whether a renal injury in a subject is prerenal, intrinsic renal, or postrenal; and/or further subdividing these classes into subclasses such as acute tubular injury, acute glomerulonephritis acute tubulointerstitial nephritis, acute vascular nephropathy, or infiltrative disease; and/or assigning a likelihood that a subject will progress to a particular RIFLE stage, and the assay result(s), for example a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and/or Tyrosine-protein kinase receptor UFO, is/are correlated to the injury classification for the subject. For example, the measured concentration may be compared to a threshold value, and when the measured concentration is above the threshold, a particular classification is assigned; alternatively, when the measured concentration is below the threshold, a different classification may be assigned to the subject. 
     A variety of methods may be used by the skilled artisan to arrive at a desired threshold value for use in these methods. For example, the threshold value may be determined from a population of normal subjects by selecting a concentration representing the 75 th , 85 th , 90 th , 95 th , or 99 th  percentile of a kidney injury marker measured in such normal subjects. Alternatively, the threshold value may be determined from a “diseased” population of subjects, e.g., those suffering from an injury or having a predisposition for an injury (e.g., progression to ARF or some other clinical outcome such as death, dialysis, renal transplantation, etc.), by selecting a concentration representing the 75 th , 85 th , 90 th , 95 th , or 99 th  percentile of a kidney injury marker measured in such subjects. In another alternative, the threshold value may be determined from a prior measurement of a kidney injury marker in the same subject; that is, a temporal change in the level of a kidney injury marker in the subject may be used to assign risk to the subject. 
     The foregoing discussion is not meant to imply, however, that the kidney injury markers of the present invention must be compared to corresponding individual thresholds. Methods for combining assay results can comprise the use of multivariate logistical regression, loglinear modeling, neural network analysis, n-of-m analysis, decision tree analysis, calculating ratios of markers, etc. This list is not meant to be limiting. In these methods, a composite result which is determined by combining individual markers may be treated as if it is itself a marker; that is, a threshold may be determined for the composite result as described herein for individual markers, and the composite result for an individual patient compared to this threshold. 
     The ability of a particular test to distinguish two populations can be established using ROC analysis. For example, ROC curves established from a “first” subpopulation which is predisposed to one or more future changes in renal status, and a “second” subpopulation which is not so predisposed can be used to calculate a ROC curve, and the area under the curve provides a measure of the quality of the test. Preferably, the tests described herein provide a ROC curve area greater than 0.5, preferably at least 0.6, more preferably 0.7, still more preferably at least 0.8, even more preferably at least 0.9, and most preferably at least 0.95. 
     In certain aspects, the measured concentration of one or more kidney injury markers, or a composite of such markers, may be treated as continuous variables. For example, any particular concentration can be converted into a corresponding probability of a future reduction in renal function for the subject, the occurrence of an injury, a classification, etc. In yet another alternative, a threshold that can provide an acceptable level of specificity and sensitivity in separating a population of subjects into “bins” such as a “first” subpopulation (e.g., which is predisposed to one or more future changes in renal status, the occurrence of an injury, a classification, etc.) and a “second” subpopulation which is not so predisposed. A threshold value is selected to separate this first and second population by one or more of the following measures of test accuracy: 
     an odds ratio greater than 1, preferably at least about 2 or more or about 0.5 or less, more preferably at least about 3 or more or about 0.33 or less, still more preferably at least about 4 or more or about 0.25 or less, even more preferably at least about 5 or more or about 0.2 or less, and most preferably at least about 10 or more or about 0.1 or less;
 
a specificity of greater than 0.5, preferably at least about 0.6, more preferably at least about 0.7, still more preferably at least about 0.8, even more preferably at least about 0.9 and most preferably at least about 0.95, with a corresponding sensitivity greater than 0.2, preferably greater than about 0.3, more preferably greater than about 0.4, still more preferably at least about 0.5, even more preferably about 0.6, yet more preferably greater than about 0.7, still more preferably greater than about 0.8, more preferably greater than about 0.9, and most preferably greater than about 0.95;
 
a sensitivity of greater than 0.5, preferably at least about 0.6, more preferably at least about 0.7, still more preferably at least about 0.8, even more preferably at least about 0.9 and most preferably at least about 0.95, with a corresponding specificity greater than 0.2, preferably greater than about 0.3, more preferably greater than about 0.4, still more preferably at least about 0.5, even more preferably about 0.6, yet more preferably greater than about 0.7, still more preferably greater than about 0.8, more preferably greater than about 0.9, and most preferably greater than about 0.95;
 
at least about 75% sensitivity, combined with at least about 75% specificity;
 
a positive likelihood ratio (calculated as sensitivity/(1-specificity)) of greater than 1, at least about 2, more preferably at least about 3, still more preferably at least about 5, and most preferably at least about 10; or
 
a negative likelihood ratio (calculated as (1-sensitivity)/specificity) of less than 1, less than or equal to about 0.5, more preferably less than or equal to about 0.3, and most preferably less than or equal to about 0.1.
 
The term “about” in the context of any of the above measurements refers to +/−5% of a given measurement.
 
     Multiple thresholds may also be used to assess renal status in a subject. For example, a “first” subpopulation which is predisposed to one or more future changes in renal status, the occurrence of an injury, a classification, etc., and a “second” subpopulation which is not so predisposed can be combined into a single group. This group is then subdivided into three or more equal parts (known as tertiles, quartiles, quintiles, etc., depending on the number of subdivisions). An odds ratio is assigned to subjects based on which subdivision they fall into. If one considers a tertile, the lowest or highest tertile can be used as a reference for comparison of the other subdivisions. This reference subdivision is assigned an odds ratio of 1. The second tertile is assigned an odds ratio that is relative to that first tertile. That is, someone in the second tertile might be 3 times more likely to suffer one or more future changes in renal status in comparison to someone in the first tertile. The third tertile is also assigned an odds ratio that is relative to that first tertile. 
     In certain embodiments, the assay method is an immunoassay. Antibodies for use in such assays will specifically bind a full length kidney injury marker of interest, and may also bind one or more polypeptides that are “related” thereto, as that term is defined hereinafter. Numerous immunoassay formats are known to those of skill in the art. Preferred body fluid samples are selected from the group consisting of urine, blood, serum, saliva, tears, and plasma. 
     The foregoing method steps should not be interpreted to mean that the kidney injury marker assay result(s) is/are used in isolation in the methods described herein. Rather, additional variables or other clinical indicia may be included in the methods described herein. For example, a risk stratification, diagnostic, classification, monitoring, etc. method may combine the assay result(s) with one or more variables measured for the subject selected from the group consisting of demographic information (e.g., weight, sex, age, race), medical history (e.g., family history, type of surgery, pre-existing disease such as aneurism, congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, or sepsis, type of toxin exposure such as NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin), clinical variables (e.g., blood pressure, temperature, respiration rate), risk scores (APACHE score, PREDICT score, TIMI Risk Score for UA/NSTEMI, Framingham Risk Score), a glomerular filtration rate, an estimated glomerular filtration rate, a urine production rate, a serum or plasma creatinine concentration, a urine creatinine concentration, a fractional excretion of sodium, a urine sodium concentration, a urine creatinine to serum or plasma creatinine ratio, a urine specific gravity, a urine osmolality, a urine urea nitrogen to plasma urea nitrogen ratio, a plasma BUN to creatinine ratio, a renal failure index calculated as urine sodium/(urine creatinine/plasma creatinine), a serum or plasma neutrophil gelatinase (NGAL) concentration, a urine NGAL concentration, a serum or plasma cystatin C concentration, a serum or plasma cardiac troponin concentration, a serum or plasma BNP concentration, a serum or plasma NTproBNP concentration, and a serum or plasma proBNP concentration. Other measures of renal function which may be combined with one or more kidney injury marker assay result(s) are described hereinafter and in Harrison&#39;s Principles of Internal Medicine, 17 th  Ed., McGraw Hill, New York, pages 1741-1830, and Current Medical Diagnosis &amp; Treatment 2008, 47 th  Ed, McGraw Hill, New York, pages 785-815, each of which are hereby incorporated by reference in their entirety. 
     When more than one marker is measured, the individual markers may be measured in samples obtained at the same time, or may be determined from samples obtained at different (e.g., an earlier or later) times. The individual markers may also be measured on the same or different body fluid samples. For example, one kidney injury marker may be measured in a serum or plasma sample and another kidney injury marker may be measured in a urine sample. In addition, assignment of a likelihood may combine an individual kidney injury marker assay result with temporal changes in one or more additional variables. 
     In various related aspects, the present invention also relates to devices and kits for performing the methods described herein. Suitable kits comprise reagents sufficient for performing an assay for at least one of the described kidney injury markers, together with instructions for performing the described threshold comparisons. 
     In certain embodiments, reagents for performing such assays are provided in an assay device, and such assay devices may be included in such a kit. Preferred reagents can comprise one or more solid phase antibodies, the solid phase antibody comprising antibody that detects the intended biomarker target(s) bound to a solid support. In the case of sandwich immunoassays, such reagents can also include one or more detectably labeled antibodies, the detectably labeled antibody comprising antibody that detects the intended biomarker target(s) bound to a detectable label. Additional optional elements that may be provided as part of an assay device are described hereinafter. 
     Detectable labels may include molecules that are themselves detectable (e.g., fluorescent moieties, electrochemical labels, ecl (electrochemical luminescence) labels, metal chelates, colloidal metal particles, etc.) as well as molecules that may be indirectly detected by production of a detectable reaction product (e.g., enzymes such as horseradish peroxidase, alkaline phosphatase, etc.) or through the use of a specific binding molecule which itself may be detectable (e.g., a labeled antibody that binds to the second antibody, biotin, digoxigenin, maltose, oligohistidine, 2,4-dintrobenzene, phenylarsenate, ssDNA, dsDNA, etc.). 
     Generation of a signal from the signal development element can be performed using various optical, acoustical, and electrochemical methods well known in the art. Examples of detection modes include fluorescence, radiochemical detection, reflectance, absorbance, amperometry, conductance, impedance, interferometry, ellipsometry, etc. In certain of these methods, the solid phase antibody is coupled to a transducer (e.g., a diffraction grating, electrochemical sensor, etc) for generation of a signal, while in others, a signal is generated by a transducer that is spatially separate from the solid phase antibody (e.g., a fluorometer that employs an excitation light source and an optical detector). This list is not meant to be limiting. Antibody-based biosensors may also be employed to determine the presence or amount of analytes that optionally eliminate the need for a labeled molecule. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention relates to methods and compositions for diagnosis, differential diagnosis, risk stratification, monitoring, classifying and determination of treatment regimens in subjects suffering or at risk of suffering from injury to renal function, reduced renal function and/or acute renal failure through measurement of one or more kidney injury markers. In various embodiments, a measured concentration of one or more markers selected from the group consisting of C-C motif chemokine 16, C-C motif chemokine 14, and Tyrosine-protein kinase receptor UFO or one or more markers related thereto, and optionally one or more additional kidney injury markers known in the art, are correlated to the renal status of the subject. 
     For purposes of this document, the following definitions apply: 
     As used herein, an “injury to renal function” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) measurable reduction in a measure of renal function. Such an injury may be identified, for example, by a decrease in glomerular filtration rate or estimated GFR, a reduction in urine output, an increase in serum creatinine, an increase in serum cystatin C, a requirement for renal replacement therapy, etc. “Improvement in Renal Function” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) measurable increase in a measure of renal function. Preferred methods for measuring and/or estimating GFR are described hereinafter.
 
As used herein, “reduced renal function” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) reduction in kidney function identified by an absolute increase in serum creatinine of greater than or equal to 0.1 mg/dL (≥8.8 μmol/L), a percentage increase in serum creatinine of greater than or equal to 20% (1.2-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour).
 
As used herein, “acute renal failure” or “ARF” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) reduction in kidney function identified by an absolute increase in serum creatinine of greater than or equal to 0.3 mg/dl (≥26.4 μmol/l), a percentage increase in serum creatinine of greater than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for at least 6 hours). This term is synonymous with “acute kidney injury” or “AKI.”
 
     In this regard, the skilled artisan will understand that the signals obtained from an immunoassay are a direct result of complexes formed between one or more antibodies and the target biomolecule (i.e., the analyte) and polypeptides containing the necessary epitope(s) to which the antibodies bind. While such assays may detect the full length biomarker and the assay result be expressed as a concentration of a biomarker of interest, the signal from the assay is actually a result of all such “immunoreactive” polypeptides present in the sample. Expression of biomarkers may also be determined by means other than immunoassays, including protein measurements (such as dot blots, western blots, chromatographic methods, mass spectrometry, etc.) and nucleic acid measurements (mRNA quatitation). This list is not meant to be limiting. 
     As used herein, the term “C-C motif chemokine 16” refers to one or more polypeptides present in a biological sample that are derived from the C-C motif chemokine 16 precursor (human sequence: Swiss-Prot 015467 (SEQ ID NO: 1)): 
     
       
         
           
               
               
               
            
               
                 MKVSEAALSL LVLILIITSA SRSQPKVPEW VNTPSTCCLK YYEKVLPRRL 
                 50 
                   
               
               
                   
               
               
                 VVGYRKALNC HLPAIIFVTK RNREVCTNPN DDWVQEYIKD PNLPLLPTRN 
                 100 
               
               
                   
               
               
                 LSTVKIITAK NGQPQLLNSQ 
                 120 
               
            
           
         
       
     
     The following domains have been identified in C-C motif chemokine 16: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
                  1-23 
                 23 
                 Signal peptide 
               
               
                   
                 24-120 
                 97 
                 C-C motif chemokine 16 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “C-C motif chemokine 14” refers to one or more polypeptides present in a biological sample that are derived from the C-C motif chemokine 14 precursor (human sequence: Swiss-Prot Q16627 (SEQ ID NO: 1)): 
     
       
         
           
               
               
               
            
               
                 MKISVAAIPE FLLITIALGT KTESSSRGPY HPSECCFTYT TYKIPRQRIM 
                 50 
                   
               
               
                   
               
               
                 DYYETNSQCS KPGIVFITKR GHSVCTNPSD KWVQDYIKDM KEN 
                 93 
               
            
           
         
       
     
     The following domains have been identified in C-C motif chemokine 14: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
                  1-19 
                 19 
                 Signal peptide 
               
               
                   
                   
               
               
                   
                 20-93 
                 74 
                 C-C motif chemokine 14 
               
               
                   
                   
               
               
                   
                 22-93 
                 72 
                 HCC-1(3-74) 
               
               
                   
                   
               
               
                   
                 23-93 
                 71 
                 HCC-1(4-74) 
               
               
                   
                   
               
               
                   
                 28-93 
                 66 
                 HCC-1(9-74) 
               
               
                   
                   
               
               
                   
                 27 
                   
                 R → QTGGKPKVVKIQLKLVG 
               
               
                   
                   
                   
                 (SEQ ID NO: 2) in isoform 2 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “Tyrosine-protein kinase receptor UFO” refers to one or more polypeptides present in a biological sample that are derived from the Tyrosine-protein kinase receptor UFO precursor (human sequence: Swiss-Prot P30530 (SEQ ID NO: 1)): 
     
       
         
           
               
               
               
            
               
                 MAWRCPRMGR VPLAWCLALC GWACMAPRGT QAEESPFVGN PGNITGARGL 
                 50 
                   
               
               
                   
               
               
                 TGTLRCQLQV QGEPPEVHWL RDGQILELAD STQTQVPLGE DEQDDWIVVS 
                 100 
               
               
                   
               
               
                 QLRITSLQLS DTGQYQCLVF LGHQTFVSQP GYVGLEGLPY FLEEPEDRTV 
                 150 
               
               
                   
               
               
                 AANTPFNLSC QAQGPPEPVD LLWLQDAVPL ATAPGHGPQR SLHVPGLNKT 
                 200 
               
               
                   
               
               
                 SSFSCEAHNA KGVTTSRTAT ITVLPQQPRN LHLVSRQPTE LEVAWTPGLS 
                 250 
               
               
                   
               
               
                 GIYPLTHCTL QAVLSNDGMG IQAGEPDPPE EPLTSQASVP PHQLRLGSLH 
                 300 
               
               
                   
               
               
                 PHTPYHIRVA CTSSQGPSSW THWLPVETPE GVPLGPPENI SATRNGSQAF 
                 350 
               
               
                   
               
               
                 VHWQEPRAPL QGTLLGYRLA YQGQDTPEVL MDIGLRQEVT LELQGDGSVS 
                 400 
               
               
                   
               
               
                 NLTVCVAAYT AAGDGPWSLP VPLEAWRPGQ AQPVHQLVKE PSTPAFSWPW 
                 450 
               
               
                   
               
               
                 WYVLLGAVVA AACVLILALF LVHRRKKETR YGEVFEPTVE RGELVVRYRV 
                 500 
               
               
                   
               
               
                 RKSYSRRTTE ATLNSLGISE ELKEKLRDVM VDRHKVALGK TLGEGEFGAV 
                 550 
               
               
                   
               
               
                 MEGQLNQDDS ILKVAVKTMK IAICTRSELE DFLSEAVCMK EFDHPNVMRL 
                 600 
               
               
                   
               
               
                 IGVCFQGSER ESFPAPVVIL PFMKHGDLHS FLLYSRLGDQ PVYLPTQMLV 
                 650 
               
               
                   
               
               
                 KFMADIASGM EYLSTKRFIH RDLAARNCML NENMSVCVAD FGLSKKIYNG 
                 700 
               
               
                   
               
               
                 DYYRQGRIAK MPVKWIAIES LADRVYTSKS DVWSFGVTMW EIATRGQTPY 
                 750 
               
               
                   
               
               
                 PGVENSEIYD YLRQGNRLKQ PADCLDGLYA LMSRCWELNP QDRPSFTELR 
                 800 
               
               
                   
               
               
                 EDLENTLKAL PPAQEPDEIL YVNMDEGGGY PEPPGAAGGA DPPTQPDPKD 
                 850 
               
               
                   
               
               
                 SCSCLTAAEV HPAGRYVLCP STTPSPAQPA DRGSPAAPGQ EDGA 
                 894 
               
            
           
         
       
     
     In certain embodiments, the Tyrosine-protein kinase receptor UFO assay detects one or more soluble forms of Tyrosine-protein kinase receptor UFO. Tyrosine-protein kinase receptor UFO is a single-pass membrane protein having an extracellular domain which may be found in Tyrosine-protein kinase receptor UFO forms of Tyrosine-protein kinase receptor UFO generated by proteolysis of the membrane-bound form or by alternative splicing. In the case of an immunoassay, one or more antibodies that bind to epitopes within an extracellular domain may be used to detect these Tyrosine-protein kinase receptor UFO form(s). The following domains have been identified in Tyrosine-protein kinase receptor UFO: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
                   1-25 
                  25 
                 Signal peptide 
               
               
                   
                  26-894 
                 869 
                 Tyrosine-protein kinase receptor UFO 
               
               
                   
                 473-894 
                 422 
                 cytoplasmic domain 
               
               
                   
                 452-472 
                  21 
                 transmembrane domain 
               
               
                   
                  26-451 
                 426 
                 extracellular domain 
               
               
                   
                 429-437 
                   
                 Missing in isoform 2 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “relating a signal to the presence or amount” of an analyte reflects this understanding. Assay signals are typically related to the presence or amount of an analyte through the use of a standard curve calculated using known concentrations of the analyte of interest. As the term is used herein, an assay is “configured to detect” an analyte if an assay can generate a detectable signal indicative of the presence or amount of a physiologically relevant concentration of the analyte. Because an antibody epitope is on the order of 8 amino acids, an immunoassay configured to detect a marker of interest will also detect polypeptides related to the marker sequence, so long as those polypeptides contain the epitope(s) necessary to bind to the antibody or antibodies used in the assay. 
     The term “related marker” as used herein with regard to a biomarker such as one of the kidney injury markers described herein refers to one or more fragments, variants, etc., of a particular marker or its biosynthetic parent that may be detected as a surrogate for the marker itself or as independent biomarkers. The term also refers to one or more polypeptides present in a biological sample that are derived from the biomarker precursor complexed to additional species, such as binding proteins, receptors, heparin, lipids, sugars, etc. 
     The term “positive going” marker as that term is used herein refer to a marker that is determined to be elevated in subjects suffering from a disease or condition, relative to subjects not suffering from that disease or condition. The term “negative going” marker as that term is used herein refer to a marker that is determined to be reduced in subjects suffering from a disease or condition, relative to subjects not suffering from that disease or condition. 
     The term “subject” as used herein refers to a human or non-human organism. Thus, the methods and compositions described herein are applicable to both human and veterinary disease. Further, while a subject is preferably a living organism, the invention described herein may be used in post-mortem analysis as well. Preferred subjects are humans, and most preferably “patients,” which as used herein refers to living humans that are receiving medical care for a disease or condition. This includes persons with no defined illness who are being investigated for signs of pathology. 
     Preferably, an analyte is measured in a sample. Such a sample may be obtained from a subject, or may be obtained from biological materials intended to be provided to the subject. For example, a sample may be obtained from a kidney being evaluated for possible transplantation into a subject, and an analyte measurement used to evaluate the kidney for preexisting damage. Preferred samples are body fluid samples. 
     The term “body fluid sample” as used herein refers to a sample of bodily fluid obtained for the purpose of diagnosis, prognosis, classification or evaluation of a subject of interest, such as a patient or transplant donor. In certain embodiments, such a sample may be obtained for the purpose of determining the outcome of an ongoing condition or the effect of a treatment regimen on a condition. Preferred body fluid samples include blood, serum, plasma, cerebrospinal fluid, urine, saliva, sputum, and pleural effusions. In addition, one of skill in the art would realize that certain body fluid samples would be more readily analyzed following a fractionation or purification procedure, for example, separation of whole blood into serum or plasma components. 
     The term “diagnosis” as used herein refers to methods by which the skilled artisan can estimate and/or determine the probability (“a likelihood”) of whether or not a patient is suffering from a given disease or condition. In the case of the present invention, “diagnosis” includes using the results of an assay, most preferably an immunoassay, for a kidney injury marker of the present invention, optionally together with other clinical characteristics, to arrive at a diagnosis (that is, the occurrence or nonoccurrence) of an acute renal injury or ARF for the subject from which a sample was obtained and assayed. That such a diagnosis is “determined” is not meant to imply that the diagnosis is 100% accurate. Many biomarkers are indicative of multiple conditions. The skilled clinician does not use biomarker results in an informational vacuum, but rather test results are used together with other clinical indicia to arrive at a diagnosis. Thus, a measured biomarker level on one side of a predetermined diagnostic threshold indicates a greater likelihood of the occurrence of disease in the subject relative to a measured level on the other side of the predetermined diagnostic threshold. 
     Similarly, a prognostic risk signals a probability (“a likelihood”) that a given course or outcome will occur. A level or a change in level of a prognostic indicator, which in turn is associated with an increased probability of morbidity (e.g., worsening renal function, future ARF, or death) is referred to as being “indicative of an increased likelihood” of an adverse outcome in a patient. 
     Marker Assays 
     In general, immunoassays involve contacting a sample containing or suspected of containing a biomarker of interest with at least one antibody that specifically binds to the biomarker. A signal is then generated indicative of the presence or amount of complexes formed by the binding of polypeptides in the sample to the antibody. The signal is then related to the presence or amount of the biomarker in the sample. Numerous methods and devices are well known to the skilled artisan for the detection and analysis of biomarkers. See, e.g., U.S. Pat. Nos. 6,143,576; 6,113,855; 6,019,944; 5,985,579; 5,947,124; 5,939,272; 5,922,615; 5,885,527; 5,851,776; 5,824,799; 5,679,526; 5,525,524; and 5,480,792, and  The Immunoassay Handbook , David Wild, ed. Stockton Press, New York, 1994, each of which is hereby incorporated by reference in its entirety, including all tables, figures and claims. 
     The assay devices and methods known in the art can utilize labeled molecules in various sandwich, competitive, or non-competitive assay formats, to generate a signal that is related to the presence or amount of the biomarker of interest. Suitable assay formats also include chromatographic, mass spectrographic, and protein “blotting” methods. Additionally, certain methods and devices, such as biosensors and optical immunoassays, may be employed to determine the presence or amount of analytes without the need for a labeled molecule. See, e.g., U.S. Pat. Nos. 5,631,171; and 5,955,377, each of which is hereby incorporated by reference in its entirety, including all tables, figures and claims. One skilled in the art also recognizes that robotic instrumentation including but not limited to Beckman ACCESS®, Abbott AXSYM®, Roche ELECSYS®, Dade Behring STRATUS® systems are among the immunoassay analyzers that are capable of performing immunoassays. But any suitable immunoassay may be utilized, for example, enzyme-linked immunoassays (ELISA), radioimmunoassays (RIAs), competitive binding assays, and the like. 
     Antibodies or other polypeptides may be immobilized onto a variety of solid supports for use in assays. Solid phases that may be used to immobilize specific binding members include those developed and/or used as solid phases in solid phase binding assays. Examples of suitable solid phases include membrane filters, cellulose-based papers, beads (including polymeric, latex and paramagnetic particles), glass, silicon wafers, microparticles, nanoparticles, TentaGels, AgroGels, PEGA gels, SPOCC gels, and multiple-well plates. An assay strip could be prepared by coating the antibody or a plurality of antibodies in an array on solid support. This strip could then be dipped into the test sample and then processed quickly through washes and detection steps to generate a measurable signal, such as a colored spot. Antibodies or other polypeptides may be bound to specific zones of assay devices either by conjugating directly to an assay device surface, or by indirect binding. In an example of the later case, antibodies or other polypeptides may be immobilized on particles or other solid supports, and that solid support immobilized to the device surface. 
     Biological assays require methods for detection, and one of the most common methods for quantitation of results is to conjugate a detectable label to a protein or nucleic acid that has affinity for one of the components in the biological system being studied. Detectable labels may include molecules that are themselves detectable (e.g., fluorescent moieties, electrochemical labels, metal chelates, etc.) as well as molecules that may be indirectly detected by production of a detectable reaction product (e.g., enzymes such as horseradish peroxidase, alkaline phosphatase, etc.) or by a specific binding molecule which itself may be detectable (e.g., biotin, digoxigenin, maltose, oligohistidine, 2,4-dintrobenzene, phenylarsenate, ssDNA, dsDNA, etc.). 
     Preparation of solid phases and detectable label conjugates often comprise the use of chemical cross-linkers. Cross-linking reagents contain at least two reactive groups, and are divided generally into homofunctional cross-linkers (containing identical reactive groups) and heterofunctional cross-linkers (containing non-identical reactive groups). Homobifunctional cross-linkers that couple through amines, sulfhydryls or react non-specifically are available from many commercial sources. Maleimides, alkyl and aryl halides, alpha-haloacyls and pyridyl disulfides are thiol reactive groups. Maleimides, alkyl and aryl halides, and alpha-haloacyls react with sulfhydryls to form thiol ether bonds, while pyridyl disulfides react with sulfhydryls to produce mixed disulfides. The pyridyl disulfide product is cleavable. Imidoesters are also very useful for protein-protein cross-links. A variety of heterobifunctional cross-linkers, each combining different attributes for successful conjugation, are commercially available. 
     In certain aspects, the present invention provides kits for the analysis of the described kidney injury markers. The kit comprises reagents for the analysis of at least one test sample which comprise at least one antibody that a kidney injury marker. The kit can also include devices and instructions for performing one or more of the diagnostic and/or prognostic correlations described herein. Preferred kits will comprise an antibody pair for performing a sandwich assay, or a labeled species for performing a competitive assay, for the analyte. Preferably, an antibody pair comprises a first antibody conjugated to a solid phase and a second antibody conjugated to a detectable label, wherein each of the first and second antibodies that bind a kidney injury marker. Most preferably each of the antibodies are monoclonal antibodies. The instructions for use of the kit and performing the correlations can be in the form of labeling, which refers to any written or recorded material that is attached to, or otherwise accompanies a kit at any time during its manufacture, transport, sale or use. For example, the term labeling encompasses advertising leaflets and brochures, packaging materials, instructions, audio or video cassettes, computer discs, as well as writing imprinted directly on kits. 
     Antibodies 
     The term “antibody” as used herein refers to a peptide or polypeptide derived from, modeled after or substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, capable of specifically binding an antigen or epitope. See, e.g. Fundamental Immunology, 3rd Edition, W. E. Paul, ed., Raven Press, N.Y. (1993); Wilson (1994; J. Immunol. Methods 175:267-273; Yarmush (1992) J. Biochem. Biophys. Methods 25:85-97. The term antibody includes antigen-binding portions, i.e., “antigen binding sites,” (e.g., fragments, subsequences, complementarity determining regions (CDRs)) that retain capacity to bind antigen, including (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR). Single chain antibodies are also included by reference in the term “antibody.” 
     Antibodies used in the immunoassays described herein preferably specifically bind to a kidney injury marker of the present invention. The term “specifically binds” is not intended to indicate that an antibody binds exclusively to its intended target since, as noted above, an antibody binds to any polypeptide displaying the epitope(s) to which the antibody binds. Rather, an antibody “specifically binds” if its affinity for its intended target is about 5-fold greater when compared to its affinity for a non-target molecule which does not display the appropriate epitope(s). Preferably the affinity of the antibody will be at least about 5 fold, preferably 10 fold, more preferably 25-fold, even more preferably 50-fold, and most preferably 100-fold or more, greater for a target molecule than its affinity for a non-target molecule. In preferred embodiments, Preferred antibodies bind with affinities of at least about 10 7  M −1 , and preferably between about 10 8  M −1  to about 10 9  M −1 , about 10 9  M −1  to about 10 10  M −1 , or about 10 10  M −1  to about 10 12  M −1 . 
     Affinity is calculated as K d =k off /k on  (k off  is the dissociation rate constant, K on  is the association rate constant and K d  is the equilibrium constant). Affinity can be determined at equilibrium by measuring the fraction bound (r) of labeled ligand at various concentrations (c). The data are graphed using the Scatchard equation: r/c=K(n−r): where r=moles of bound ligand/mole of receptor at equilibrium; c=free ligand concentration at equilibrium; K=equilibrium association constant; and n=number of ligand binding sites per receptor molecule. By graphical analysis, r/c is plotted on the Y-axis versus r on the X-axis, thus producing a Scatchard plot. Antibody affinity measurement by Scatchard analysis is well known in the art. See, e.g., van Erp et al.,  J. Immunoassay  12: 425-43, 1991; Nelson and Griswold,  Comput. Methods Programs Biomed.  27: 65-8, 1988. 
     The term “epitope” refers to an antigenic determinant capable of specific binding to an antibody. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. Conformational and nonconformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. 
     Numerous publications discuss the use of phage display technology to produce and screen libraries of polypeptides for binding to a selected analyte. See, e.g, Cwirla et al.,  Proc. Natl. Acad. Sci. USA  87, 6378-82, 1990; Devlin et al.,  Science  249, 404-6, 1990, Scott and Smith,  Science  249, 386-88, 1990; and Ladner et al., U.S. Pat. No. 5,571,698. A basic concept of phage display methods is the establishment of a physical association between DNA encoding a polypeptide to be screened and the polypeptide. This physical association is provided by the phage particle, which displays a polypeptide as part of a capsid enclosing the phage genome which encodes the polypeptide. The establishment of a physical association between polypeptides and their genetic material allows simultaneous mass screening of very large numbers of phage bearing different polypeptides. Phage displaying a polypeptide with affinity to a target bind to the target and these phage are enriched by affinity screening to the target. The identity of polypeptides displayed from these phage can be determined from their respective genomes. Using these methods a polypeptide identified as having a binding affinity for a desired target can then be synthesized in bulk by conventional means. See, e.g., U.S. Pat. No. 6,057,098, which is hereby incorporated in its entirety, including all tables, figures, and claims. 
     The antibodies that are generated by these methods may then be selected by first screening for affinity and specificity with the purified polypeptide of interest and, if required, comparing the results to the affinity and specificity of the antibodies with polypeptides that are desired to be excluded from binding. The screening procedure can involve immobilization of the purified polypeptides in separate wells of microtiter plates. The solution containing a potential antibody or groups of antibodies is then placed into the respective microtiter wells and incubated for about 30 min to 2 h. The microtiter wells are then washed and a labeled secondary antibody (for example, an anti-mouse antibody conjugated to alkaline phosphatase if the raised antibodies are mouse antibodies) is added to the wells and incubated for about 30 min and then washed. Substrate is added to the wells and a color reaction will appear where antibody to the immobilized polypeptide(s) are present. 
     The antibodies so identified may then be further analyzed for affinity and specificity in the assay design selected. In the development of immunoassays for a target protein, the purified target protein acts as a standard with which to judge the sensitivity and specificity of the immunoassay using the antibodies that have been selected. Because the binding affinity of various antibodies may differ; certain antibody pairs (e.g., in sandwich assays) may interfere with one another sterically, etc., assay performance of an antibody may be a more important measure than absolute affinity and specificity of an antibody. 
     Assay Correlations 
     The term “correlating” as used herein in reference to the use of biomarkers refers to comparing the presence or amount of the biomarker(s) in a patient to its presence or amount in persons known to suffer from, or known to be at risk of, a given condition; or in persons known to be free of a given condition. Often, this takes the form of comparing an assay result in the form of a biomarker concentration to a predetermined threshold selected to be indicative of the occurrence or nonoccurrence of a disease or the likelihood of some future outcome. 
     Selecting a diagnostic threshold involves, among other things, consideration of the probability of disease, distribution of true and false diagnoses at different test thresholds, and estimates of the consequences of treatment (or a failure to treat) based on the diagnosis. For example, when considering administering a specific therapy which is highly efficacious and has a low level of risk, few tests are needed because clinicians can accept substantial diagnostic uncertainty. On the other hand, in situations where treatment options are less effective and more risky, clinicians often need a higher degree of diagnostic certainty. Thus, cost/benefit analysis is involved in selecting a diagnostic threshold. 
     Suitable thresholds may be determined in a variety of ways. For example, one recommended diagnostic threshold for the diagnosis of acute myocardial infarction using cardiac troponin is the 97.5 th  percentile of the concentration seen in a normal population. Another method may be to look at serial samples from the same patient, where a prior “baseline” result is used to monitor for temporal changes in a biomarker level. 
     Population studies may also be used to select a decision threshold. Reciever Operating Characteristic (“ROC”) arose from the field of signal dectection theory developed during World War II for the analysis of radar images, and ROC analysis is often used to select a threshold able to best distinguish a “diseased” subpopulation from a “nondiseased” subpopulation. A false positive in this case occurs when the person tests positive, but actually does not have the disease. A false negative, on the other hand, occurs when the person tests negative, suggesting they are healthy, when they actually do have the disease. To draw a ROC curve, the true positive rate (TPR) and false positive rate (FPR) are determined as the decision threshold is varied continuously. Since TPR is equivalent with sensitivity and FPR is equal to 1-specificity, the ROC graph is sometimes called the sensitivity vs (1-specificity) plot. A perfect test will have an area under the ROC curve of 1.0; a random test will have an area of 0.5. A threshold is selected to provide an acceptable level of specificity and sensitivity. 
     In this context, “diseased” is meant to refer to a population having one characteristic (the presence of a disease or condition or the occurrence of some outcome) and “nondiseased” is meant to refer to a population lacking the characteristic. While a single decision threshold is the simplest application of such a method, multiple decision thresholds may be used. For example, below a first threshold, the absence of disease may be assigned with relatively high confidence, and above a second threshold the presence of disease may also be assigned with relatively high confidence. Between the two thresholds may be considered indeterminate. This is meant to be exemplary in nature only. 
     In addition to threshold comparisons, other methods for correlating assay results to a patient classification (occurrence or nonoccurrence of disease, likelihood of an outcome, etc.) include decision trees, rule sets, Bayesian methods, and neural network methods. These methods can produce probability values representing the degree to which a subject belongs to one classification out of a plurality of classifications. 
     Measures of test accuracy may be obtained as described in Fischer et al.,  Intensive Care Med.  29: 1043-51, 2003, and used to determine the effectiveness of a given biomarker. These measures include sensitivity and specificity, predictive values, likelihood ratios, diagnostic odds ratios, and ROC curve areas. The area under the curve (“AUC”) of a ROC plot is equal to the probability that a classifier will rank a randomly chosen positive instance higher than a randomly chosen negative one. The area under the ROC curve may be thought of as equivalent to the Mann-Whitney U test, which tests for the median difference between scores obtained in the two groups considered if the groups are of continuous data, or to the Wilcoxon test of ranks. 
     As discussed above, suitable tests may exhibit one or more of the following results on these various measures: a specificity of greater than 0.5, preferably at least 0.6, more preferably at least 0.7, still more preferably at least 0.8, even more preferably at least 0.9 and most preferably at least 0.95, with a corresponding sensitivity greater than 0.2, preferably greater than 0.3, more preferably greater than 0.4, still more preferably at least 0.5, even more preferably 0.6, yet more preferably greater than 0.7, still more preferably greater than 0.8, more preferably greater than 0.9, and most preferably greater than 0.95; a sensitivity of greater than 0.5, preferably at least 0.6, more preferably at least 0.7, still more preferably at least 0.8, even more preferably at least 0.9 and most preferably at least 0.95, with a corresponding specificity greater than 0.2, preferably greater than 0.3, more preferably greater than 0.4, still more preferably at least 0.5, even more preferably 0.6, yet more preferably greater than 0.7, still more preferably greater than 0.8, more preferably greater than 0.9, and most preferably greater than 0.95; at least 75% sensitivity, combined with at least 75% specificity; a ROC curve area of greater than 0.5, preferably at least 0.6, more preferably 0.7, still more preferably at least 0.8, even more preferably at least 0.9, and most preferably at least 0.95; an odds ratio different from 1, preferably at least about 2 or more or about 0.5 or less, more preferably at least about 3 or more or about 0.33 or less, still more preferably at least about 4 or more or about 0.25 or less, even more preferably at least about 5 or more or about 0.2 or less, and most preferably at least about 10 or more or about 0.1 or less; a positive likelihood ratio (calculated as sensitivity/(1-specificity)) of greater than 1, at least 2, more preferably at least 3, still more preferably at least 5, and most preferably at least 10; and or a negative likelihood ratio (calculated as (1-sensitivity)/specificity) of less than 1, less than or equal to 0.5, more preferably less than or equal to 0.3, and most preferably less than or equal to 0.1 
     Additional clinical indicia may be combined with the kidney injury marker assay result(s) of the present invention. These include other biomarkers related to renal status. Examples include the following, which recite the common biomarker name, followed by the Swiss-Prot entry number for that biomarker or its parent: Actin (P68133); Adenosine deaminase binding protein (DPP4, P27487); Alpha-1-acid glycoprotein 1 (P02763); Alpha-1-microglobulin (P02760); Albumin (P02768); Angiotensinogenase (Renin, P00797); Annexin A2 (P07355); Beta-glucuronidase (P08236); B-2-microglobulin (P61769); Beta-galactosidase (P16278); BMP-7 (P18075); Brain natriuretic peptide (proBNP, BNP-32, NTproBNP; P16860); Calcium-binding protein Beta (S100-beta, P04271); Carbonic anhydrase 9 (Q16790); Casein Kinase 2 (P68400); Clusterin (P10909); Complement C3 (P01024); Cysteine-rich protein (CYR61, O00622); Cytochrome C (P99999); Epidermal growth factor (EGF, P01133); Endothelin-1 (P05305); Exosomal Fetuin-A (P02765); Fatty acid-binding protein, heart (FABP3, P05413); Fatty acid-binding protein, liver (P07148); Ferritin (light chain, P02792; heavy chain P02794); Fructose-1,6-biphosphatase (P09467); GRO-alpha (CXCL1, (P09341); Growth Hormone (P01241); Hepatocyte growth factor (P14210); Insulin-like growth factor I (P05019); Immunoglobulin G; Immunoglobulin Light Chains (Kappa and Lambda); Interferon gamma (P01308); Lysozyme (P61626); Interleukin-1alpha (P01583); Interleukin-2 (P60568); Interleukin-4 (P05112); Interleukin-9 (P15248); Interleukin-12p40 (P29460); Interleukin-13 (P35225); Interleukin-16 (Q14005); L1 cell adhesion molecule (P32004); Lactate dehydrogenase (P00338); Leucine Aminopeptidase (P28838); Meprin A-alpha subunit (Q16819); Meprin A-beta subunit (Q16820); Midkine (P21741); MIP2-alpha (CXCL2, P19875); MMP-2 (P08253); MMP-9 (P14780); Netrin-1 (O95631); Neutral endopeptidase (P08473); Osteopontin (O14788); Renal papillary antigen 1 (RPA1); Renal papillary antigen 2 (RPA2); Retinol binding protein (P09455); Ribonuclease; S100 calcium-binding protein A6 (P06703); Serum Amyloid P Component (P02743); Sodium/Hydrogen exchanger isoform (NHE3, P48764); Spermidine/spermine N1-acetyltransferase (P21673); TGF-Betal (P01137); Transferrin (P02787); Trefoil factor 3 (TFF3, Q07654); Toll-Like protein 4 (O00206); Total protein; Tubulointerstitial nephritis antigen (Q9UJW2); Uromodulin (Tamm-Horsfall protein, P07911). 
     For purposes of risk stratification, Adiponectin (Q15848); Alkaline phosphatase (P05186); Aminopeptidase N (P15144); CalbindinD28k (P05937); Cystatin C (P01034); 8 subunit of FIFO ATPase (P03928); Gamma-glutamyltransferase (P19440); GSTa (alpha-glutathione-S-transferase, P08263); GSTpi (Glutathione-S-transferase P; GST class-pi; P09211); IGFBP-1 (P08833); IGFBP-2 (P18065); IGFBP-6 (P24592); Integral membrane protein 1 (Itm1, P46977); Interleukin-6 (P05231); Interleukin-8 (P10145); Interleukin-18 (Q14116); IP-10 (10 kDa interferon-gamma-induced protein, P02778); IRPR (IFRD1, O00458); Isovaleryl-CoA dehydrogenase (IVD, P26440); I-TAC/CXCL11 (O14625); Keratin 19 (P08727); Kim-1 (Hepatitis A virus cellular receptor 1, 043656); L-arginine:glycine amidinotransferase (P50440); Leptin (P41159); Lipocalin2 (NGAL, P80188); MCP-1 (P13500); MIG (Gamma-interferon-induced monokine Q07325); MIP-la (P10147); MIP-3a (P78556); MIP-1beta (P13236); MIP-1d (Q16663); NAG (N-acetyl-beta-D-glucosaminidase, P54802); Organic ion transporter (OCT2, O15244); Osteoprotegerin (O14788); P8 protein (O60356); Plasminogen activator inhibitor 1 (PAI-1, P05121); ProANP (1-98) (P01160); Protein phosphatase 1-beta (PPI-beta, P62140); Rab GDI-beta (P50395); Renal kallikrein (P06870); RT1.B-1 (alpha) chain of the integral membrane protein (Q5Y7A8); soluble tumor necrosis factor receptor superfamily member 1A (sTNFR-I, P19438); soluble tumor necrosis factor receptor superfamily member 1B (sTNFR-II, P20333); Tissue inhibitor of metalloproteinases 3 (TIMP-3, P35625); uPAR (Q03405) may be combined with the kidney injury marker assay result(s) of the present invention. 
     Other clinical indicia which may be combined with the kidney injury marker assay result(s) of the present invention includes demographic information (e.g., weight, sex, age, race), medical history (e.g., family history, type of surgery, pre-existing disease such as aneurism, congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, or sepsis, type of toxin exposure such as NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin), clinical variables (e.g., blood pressure, temperature, respiration rate), risk scores (APACHE score, PREDICT score, TIMI Risk Score for UA/NSTEMI, Framingham Risk Score), a urine total protein measurement, a glomerular filtration rate, an estimated glomerular filtration rate, a urine production rate, a serum or plasma creatinine concentration, a renal papillary antigen 1 (RPA1) measurement; a renal papillary antigen 2 (RPA2) measurement; a urine creatinine concentration, a fractional excretion of sodium, a urine sodium concentration, a urine creatinine to serum or plasma creatinine ratio, a urine specific gravity, a urine osmolality, a urine urea nitrogen to plasma urea nitrogen ratio, a plasma BUN to creatnine ratio, and/or a renal failure index calculated as urine sodium/(urine creatinine/plasma creatinine). Other measures of renal function which may be combined with the kidney injury marker assay result(s) are described hereinafter and in Harrison&#39;s Principles of Internal Medicine, 17 th  Ed., McGraw Hill, New York, pages 1741-1830, and Current Medical Diagnosis &amp; Treatment 2008, 47 th  Ed, McGraw Hill, New York, pages 785-815, each of which are hereby incorporated by reference in their entirety. 
     Combining assay results/clinical indicia in this manner can comprise the use of multivariate logistical regression, loglinear modeling, neural network analysis, n-of-m analysis, decision tree analysis, etc. This list is not meant to be limiting. 
     Diagnosis of Acute Renal Failure 
     As noted above, the terms “acute renal (or kidney) injury” and “acute renal (or kidney) failure” as used herein are defined in part in terms of changes in serum creatinine from a baseline value. Most definitions of ARF have common elements, including the use of serum creatinine and, often, urine output. Patients may present with renal dysfunction without an available baseline measure of renal function for use in this comparison. In such an event, one may estimate a baseline serum creatinine value by assuming the patient initially had a normal GFR. Glomerular filtration rate (GFR) is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman&#39;s capsule per unit time. Glomerular filtration rate (GFR) can be calculated by measuring any chemical that has a steady level in the blood, and is freely filtered but neither reabsorbed nor secreted by the kidneys. GFR is typically expressed in units of ml/min: 
     
       
         
           
             GFR 
             = 
             
               
                 Urine 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 Concentration 
                 × 
                 Urine 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 Flow 
               
               
                 Plasma 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 Concentration 
               
             
           
         
       
     
     By normalizing the GFR to the body surface area, a GFR of approximately 75-100 ml/min per 1.73 m 2  can be assumed. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. 
     There are several different techniques used to calculate or estimate the glomerular filtration rate (GFR or eGFR). In clinical practice, however, creatinine clearance is used to measure GFR. Creatinine is produced naturally by the body (creatinine is a metabolite of creatine, which is found in muscle). It is freely filtered by the glomerulus, but also actively secreted by the renal tubules in very small amounts such that creatinine clearance overestimates actual GFR by 10-20%. This margin of error is acceptable considering the ease with which creatinine clearance is measured. 
     Creatinine clearance (CCr) can be calculated if values for creatinine&#39;s urine concentration (U Cr ), urine flow rate (V), and creatinine&#39;s plasma concentration (P Cr ) are known. Since the product of urine concentration and urine flow rate yields creatinine&#39;s excretion rate, creatinine clearance is also said to be its excretion rate (U Cr ×V) divided by its plasma concentration. This is commonly represented mathematically as: 
     
       
         
           
             
               C 
               Cr 
             
             = 
             
               
                 
                   U 
                   Cr 
                 
                 × 
                 V 
               
               
                 P 
                 Cr 
               
             
           
         
       
     
     Commonly a 24 hour urine collection is undertaken, from empty-bladder one morning to the contents of the bladder the following morning, with a comparative blood test then taken: 
     
       
         
           
             
               C 
               Cr 
             
             = 
             
               
                 
                   U 
                   Cr 
                 
                 × 
                 24 
                 ⁢ 
                 
                   - 
                 
                 ⁢ 
                 hour 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 volume 
               
               
                 
                   P 
                   Cr 
                 
                 × 
                 24 
                 × 
                 60 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 mins 
               
             
           
         
       
     
     To allow comparison of results between people of different sizes, the CCr is often corrected for the body surface area (BSA) and expressed compared to the average sized man as ml/min/1.73 m2. While most adults have a BSA that approaches 1.7 (1.6-1.9), extremely obese or slim patients should have their CCr corrected for their actual BSA: 
     
       
         
           
             
               C 
               
                 Cr 
                 - 
                 corrected 
               
             
             = 
             
               
                 
                   C 
                   Cr 
                 
                 × 
                 1.73 
               
               BSA 
             
           
         
       
     
     The accuracy of a creatinine clearance measurement (even when collection is complete) is limited because as glomerular filtration rate (GFR) falls creatinine secretion is increased, and thus the rise in serum creatinine is less. Thus, creatinine excretion is much greater than the filtered load, resulting in a potentially large overestimation of the GFR (as much as a twofold difference). However, for clinical purposes it is important to determine whether renal function is stable or getting worse or better. This is often determined by monitoring serum creatinine alone. Like creatinine clearance, the serum creatinine will not be an accurate reflection of GFR in the non-steady-state condition of ARF. Nonetheless, the degree to which serum creatinine changes from baseline will reflect the change in GFR. Serum creatinine is readily and easily measured and it is specific for renal function. 
     For purposes of determining urine output on a Urine output on a mL/kg/hr basis, hourly urine collection and measurement is adequate. In the case where, for example, only a cumulative 24-h output was available and no patient weights are provided, minor modifications of the RIFLE urine output criteria have been described. For example, Bagshaw et al.,  Nephrol. Dial. Transplant.  23: 1203-1210, 2008, assumes an average patient weight of 70 kg, and patients are assigned a RIFLE classification based on the following: &lt;35 mL/h (Risk), &lt;21 mL/h (Injury) or &lt;4 mL/h (Failure). 
     Selecting a Treatment Regimen 
     Once a diagnosis is obtained, the clinician can readily select a treatment regimen that is compatible with the diagnosis, such as initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, kidney transplantation, delaying or avoiding procedures that are known to be damaging to the kidney, modifying diuretic administration, initiating goal directed therapy, etc. The skilled artisan is aware of appropriate treatments for numerous diseases discussed in relation to the methods of diagnosis described herein. See, e.g., Merck Manual of Diagnosis and Therapy, 17th Ed. Merck Research Laboratories, Whitehouse Station, N J, 1999. In addition, since the methods and compositions described herein provide prognostic information, the markers of the present invention may be used to monitor a course of treatment. For example, improved or worsened prognostic state may indicate that a particular treatment is or is not efficacious. 
     One skilled in the art readily appreciates that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The examples provided herein are representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention. 
     Example 1: Contrast-Induced Nephropathy Sample Collection 
     The objective of this sample collection study is to collect samples of plasma and urine and clinical data from patients before and after receiving intravascular contrast media. Approximately 250 adults undergoing radiographic/angiographic procedures involving intravascular administration of iodinated contrast media are enrolled. To be enrolled in the study, each patient must meet all of the following inclusion criteria and none of the following exclusion criteria: 
     Inclusion Criteria 
     males and females 18 years of age or older;
 
undergoing a radiographic/angiographic procedure (such as a CT scan or coronary intervention) involving the intravascular administration of contrast media;
 
expected to be hospitalized for at least 48 hours after contrast administration.
 
able and willing to provide written informed consent for study participation and to comply with all study procedures.
 
     Exclusion Criteria 
     renal transplant recipients;
 
acutely worsening renal function prior to the contrast procedure;
 
already receiving dialysis (either acute or chronic) or in imminent need of dialysis at enrollment;
 
expected to undergo a major surgical procedure (such as involving cardiopulmonary bypass) or an additional imaging procedure with contrast media with significant risk for further renal insult within the 48 hrs following contrast administration;
 
participation in an interventional clinical study with an experimental therapy within the previous 30 days;
 
known infection with human immunodeficiency virus (HIV) or a hepatitis virus.
 
     Immediately prior to the first contrast administration (and after any pre-procedure hydration), an EDTA anti-coagulated blood sample (10 mL) and a urine sample (10 mL) are collected from each patient. Blood and urine samples are then collected at 4 (±0.5), 8 (±1), 24 (±2) 48 (±2), and 72 (±2) hrs following the last administration of contrast media during the index contrast procedure. Blood is collected via direct venipuncture or via other available venous access, such as an existing femoral sheath, central venous line, peripheral intravenous line or hep-lock. These study blood samples are processed to plasma at the clinical site, frozen and shipped to Astute Medical, Inc., San Diego, Calif. The study urine samples are frozen and shipped to Astute Medical, Inc. 
     Serum creatinine is assessed at the site immediately prior to the first contrast administration (after any pre-procedure hydration) and at 4 (±0.5), 8 (±1), 24 (±2) and 48 (±2)), and 72 (±2) hours following the last administration of contrast (ideally at the same time as the study samples are obtained). In addition, each patient&#39;s status is evaluated through day 30 with regard to additional serum and urine creatinine measurements, a need for dialysis, hospitalization status, and adverse clinical outcomes (including mortality). 
     Prior to contrast administration, each patient is assigned a risk based on the following assessment: systolic blood pressure &lt;80 mm Hg=5 points; intra-arterial balloon pump=5 points; congestive heart failure (Class III-IV or history of pulmonary edema)=5 points; age &gt;75 yrs=4 points; hematocrit level &lt;39% for men, &lt;35% for women=3 points; diabetes=3 points; contrast media volume=1 point for each 100 mL; serum creatinine level &gt;1.5 g/dL=4 points OR estimated GFR 40-60 mL/min/1.73 m 2 =2 points, 20-40 mL/min/1.73 m 2 =4 points, &lt;20 mL/min/1.73 m 2 =6 points. The risks assigned are as follows: risk for CIN and dialysis: 5 or less total points=risk of CIN—7.5%, risk of dialysis—0.04%; 6-10 total points=risk of CIN—14%, risk of dialysis—0.12%; 11-16 total points=risk of CIN—26.1%, risk of dialysis—1.09%; &gt;16 total points=risk of CIN—57.3%, risk of dialysis—12.8%. 
     Example 2: Cardiac Surgery Sample Collection 
     The objective of this sample collection study is to collect samples of plasma and urine and clinical data from patients before and after undergoing cardiovascular surgery, a procedure known to be potentially damaging to kidney function. Approximately 900 adults undergoing such surgery are enrolled. To be enrolled in the study, each patient must meet all of the following inclusion criteria and none of the following exclusion criteria: 
     Inclusion Criteria 
     males and females 18 years of age or older;
 
undergoing cardiovascular surgery;
 
Toronto/Ottawa Predictive Risk Index for Renal Replacement risk score of at least 2 (Wijeysundera et al.,  JAMA  297: 1801-9, 2007); and
 
able and willing to provide written informed consent for study participation and to comply with all study procedures.
 
     Exclusion Criteria 
     known pregnancy;
 
previous renal transplantation;
 
acutely worsening renal function prior to enrollment (e.g., any category of RIFLE criteria);
 
already receiving dialysis (either acute or chronic) or in imminent need of dialysis at enrollment;
 
currently enrolled in another clinical study or expected to be enrolled in another clinical study within 7 days of cardiac surgery that involves drug infusion or a therapeutic intervention for AKI;
 
known infection with human immunodeficiency virus (HIV) or a hepatitis virus.
 
     Within 3 hours prior to the first incision (and after any pre-procedure hydration), an EDTA anti-coagulated blood sample (10 mL), whole blood (3 mL), and a urine sample (35 mL) are collected from each patient. Blood and urine samples are then collected at 3 (±0.5), 6 (±0.5), 12 (±1), 24 (±2) and 48 (±2) hrs following the procedure and then daily on days 3 through 7 if the subject remains in the hospital. Blood is collected via direct venipuncture or via other available venous access, such as an existing femoral sheath, central venous line, peripheral intravenous line or hep-lock. These study blood samples are frozen and shipped to Astute Medical, Inc., San Diego, Calif. The study urine samples are frozen and shipped to Astute Medical, Inc. 
     Example 3: Acutely Ill Subject Sample Collection 
     The objective of this study is to collect samples from acutely ill patients. Approximately 900 adults expected to be in the ICU for at least 48 hours will be enrolled. To be enrolled in the study, each patient must meet all of the following inclusion criteria and none of the following exclusion criteria: 
     Inclusion Criteria 
     males and females 18 years of age or older;
 
Study population 1: approximately 300 patients that have at least one of:
 
shock (SBP &lt;90 mmHg and/or need for vasopressor support to maintain MAP &gt;60 mmHg and/or documented drop in SBP of at least 40 mmHg); and
 
sepsis;
 
Study population 2: approximately 300 patients that have at least one of:
 
IV antibiotics ordered in computerized physician order entry (CPOE) within 24 hours of enrollment;
 
contrast media exposure within 24 hours of enrollment;
 
increased Intra-Abdominal Pressure with acute decompensated heart failure; and
 
severe trauma as the primary reason for ICU admission and likely to be hospitalized in the ICU for 48 hours after enrollment;
 
Study population 3: approximately 300 patients
 
expected to be hospitalized through acute care setting (ICU or ED) with a known risk factor for acute renal injury (e.g. sepsis, hypotension/shock (Shock=systolic BP&lt;90 mmHg and/or the need for vasopressor support to maintain a MAP &gt;60 mmHg and/or a documented drop in SBP &gt;40 mmHg), major trauma, hemorrhage, or major surgery); and/or expected to be hospitalized to the ICU for at least 24 hours after enrollment.
 
     Exclusion Criteria 
     known pregnancy;
 
institutionalized individuals;
 
previous renal transplantation;
 
known acutely worsening renal function prior to enrollment (e.g., any category of RIFLE criteria);
 
received dialysis (either acute or chronic) within 5 days prior to enrollment or in imminent need of dialysis at the time of enrollment;
 
known infection with human immunodeficiency virus (HIV) or a hepatitis virus;
 
meets only the SBP &lt;90 mmHg inclusion criterion set forth above, and does not have shock in the attending physician&#39;s or principal investigator&#39;s opinion.
 
     After providing informed consent, an EDTA anti-coagulated blood sample (10 mL) and a urine sample (25-30 mL) are collected from each patient. Blood and urine samples are then collected at 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Blood is collected via direct venipuncture or via other available venous access, such as an existing femoral sheath, central venous line, peripheral intravenous line or hep-lock. These study blood samples are processed to plasma at the clinical site, frozen and shipped to Astute Medical, Inc., San Diego, Calif. The study urine samples are frozen and shipped to Astute Medical, Inc. 
     Example 4. Immunoassay Format 
     Analytes are measured using standard sandwich enzyme immunoassay techniques. A first antibody which binds the analyte is immobilized in wells of a 96 well polystyrene microplate. Analyte standards and test samples are pipetted into the appropriate wells and any analyte present is bound by the immobilized antibody. After washing away any unbound substances, a horseradish peroxidase-conjugated second antibody which binds the analyte is added to the wells, thereby forming sandwich complexes with the analyte (if present) and the first antibody. Following a wash to remove any unbound antibody-enzyme reagent, a substrate solution comprising tetramethylbenzidine and hydrogen peroxide is added to the wells. Color develops in proportion to the amount of analyte present in the sample. The color development is stopped and the intensity of the color is measured at 540 nm or 570 nm. An analyte concentration is assigned to the test sample by comparison to a standard curve determined from the analyte standards. Units for C-C motif chemokine 16 reported herein are ng/mL. Units for C-C motif chemokine 14 reported herein are ng/mL. Units for soluble Tyrosine-protein kinase receptor UFO reported herein are ng/mL. 
     Example 5. Apparently Healthy Donor and Chronic Disease Patient Samples 
     Human urine samples from donors with no known chronic or acute disease (“Apparently Healthy Donors”) were purchased from two vendors (Golden West Biologicals, Inc., 27625 Commerce Center Dr., Temecula, Calif. 92590 and Virginia Medical Research, Inc., 915 First Colonial Rd., Virginia Beach, Va. 23454). The urine samples were shipped and stored frozen at less than −20° C. The vendors supplied demographic information for the individual donors including gender, race (Black/White), smoking status and age. 
     Human urine samples from donors with various chronic diseases (“Chronic Disease Patients”) including congestive heart failure, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus and hypertension were purchased from Virginia Medical Research, Inc., 915 First Colonial Rd., Virginia Beach, Va. 23454. The urine samples were shipped and stored frozen at less than −20 degrees centigrade. The vendor provided a case report form for each individual donor with age, gender, race (Black/White), smoking status and alcohol use, height, weight, chronic disease(s) diagnosis, current medications and previous surgeries. 
     Example 6. Use of C-C Motif Chemokine 14 for Evaluating Renal Status in Patients Admitted to the ICU: Recovery to RIFLE 0 from RIFLE I and F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 14 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output during a period starting at 12, 24, 48, or 72 hours after sample collection or at any time within 7 days after sample collection. Two cohorts are defined to represent a “recovered” and a “non-recovered” population. “Recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0). “Non-recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is risk of injury (R), injury (I) or failure (F). If a patient dies or is placed on renal replacement therapy (RRT) within 9 days of enrollment, the patient is considered “non-recovered”. 
     The ability to distinguish the “recovered” and “non-recovered” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 6.1 
               
             
            
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 12 hours after sample collection and renal status is assessed by  
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
            
           
           
               
               
            
               
                   
                 Recovery Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                   
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                   
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.475 
                 1.19 
                 0.547 
                 1.15 
                 0.805 
                 1.04 
               
               
                 Average 
                 0.567 
                 2.10 
                 0.625 
                 2.06 
                 0.744 
                 2.02 
               
               
                 Stdev 
                 0.332 
                 2.12 
                 0.365 
                 2.11 
                 0.384 
                 2.10 
               
               
                 p (t-test) 
                   
                 6.1E−7 
                   
                 1.9E−5 
                   
                 0.0017 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 1.16 
                 7.86 
                 1.16 
                 7.86 
                 1.16 
                 7.86 
               
               
                 n (Patient) 
                 8 
                 73 
                 6 
                 75 
                 4 
                 77 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.551 
                 1.58 
                 0.557 
                 1.38 
                 0.611 
                 1.20 
               
               
                 Average 
                 0.964 
                 2.53 
                 1.01 
                 2.45 
                 1.04 
                 2.38 
               
               
                 Stdev 
                 0.898 
                 2.32 
                 0.916 
                 2.31 
                 0.939 
                 2.30 
               
               
                 p (t-test) 
                   
                 6.0E−5 
                   
                 1.7E−4 
                   
                 4.4E−4 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
               
               
                 n (Patient) 
                 30 
                 51 
                 28 
                 53 
                 26 
                 55 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.640 
                 1.33 
                 0.838 
                 1.26 
                 1.04 
                 1.19 
               
               
                 Average 
                 1.21 
                 2.18 
                 1.30 
                 2.15 
                 1.42 
                 2.09 
               
               
                 Stdev 
                 1.33 
                 2.13 
                 1.36 
                 2.13 
                 1.38 
                 2.13 
               
               
                 p (t-test) 
                   
                 0.068 
                   
                 0.13 
                   
                 0.25 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 4.74 
                 7.86 
                 4.74 
                 7.86 
                 4.74 
                 7.86 
               
               
                 n (Patient) 
                 11 
                 61 
                 10 
                 62 
                 9 
                 64 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr  
                 sCr 
                 UO 
                 sCr  
                 sCr  
                 UO  
                 sCr  
                 sCr 
                 UO  
               
               
                   
                 or UO 
                 only 
                 only 
                 or UO 
                 only 
                 only 
                 or UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.75 
                 0.71 
                 0.65 
                 0.71 
                 0.68 
                 0.61 
                 0.65 
                 0.67 
                 0.56 
               
               
                 SE 
                 0.076 
                 0.057 
                 0.084 
                 0.094 
                 0.060 
                 0.091 
                 0.13 
                 0.062 
                 0.100 
               
               
                 p Value 
                 8.8E−4 
                 2.0E−4 
                 0.076 
                 0.024 
                 0.0022 
                 0.24 
                 0.24 
                 0.0070 
                 0.57 
               
               
                 nCohort Recovered 
                 8 
                 30 
                 11 
                 6 
                 28 
                 10 
                 4 
                 26 
                 9 
               
               
                 nCohort Non-recovered 
                 73 
                 51 
                 61 
                 75 
                 53 
                 62 
                 77 
                 55 
                 64 
               
               
                 Cutoff Quartile 2 
                 0.460 
                 0.460 
                 0.525 
                 0.460 
                 0.460 
                 0.502 
                 0.460 
                 0.460 
                 0.474 
               
               
                 Sensitivity 
                  77% 
                 80% 
                 77% 
                  75% 
                 77% 
                 74% 
                  74% 
                 78% 
                 72% 
               
               
                 Specificity 
                  50% 
                 37% 
                 36% 
                  33% 
                 32% 
                 20% 
                  25% 
                 35% 
                 11% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
               
               
                 Sensitivity 
                  52% 
                 57% 
                 54% 
                  51% 
                 55% 
                 53% 
                  49% 
                 53% 
                 52% 
               
               
                 Specificity 
                  75% 
                 63% 
                 73% 
                  67% 
                 61% 
                 70% 
                  50% 
                 58% 
                 67% 
               
               
                 Cutoff Quartile 4 
                 2.87 
                 2.87 
                 2.94 
                 2.87 
                 2.87 
                 2.94 
                 2.87 
                 2.87 
                 2.91 
               
               
                 Sensitivity 
                  27% 
                 35% 
                 28% 
                  27% 
                 34% 
                 27% 
                  26% 
                 33% 
                 27% 
               
               
                 Specificity 
                 100% 
                 93% 
                 91% 
                 100% 
                 93% 
                 90% 
                 100% 
                 92% 
                 89% 
               
               
                 OR Quartile 2 
                 3.29 
                 2.37 
                 1.92 
                 1.47 
                 1.62 
                 0.719 
                 0.950 
                 1.90 
                 0.319 
               
               
                 p Value 
                 0.12 
                 0.095 
                 0.35 
                 0.67 
                 0.36 
                 0.69 
                 0.97 
                 0.22 
                 0.30 
               
               
                 Lower limit of 95% CI 
                 0.744 
                 0.861 
                 0.490 
                 0.250 
                 0.583 
                 0.138 
                 0.0934 
                 0.677 
                 0.0372 
               
               
                 Upper limit of 95% CI 
                 14.6 
                 6.55 
                 7.52 
                 8.70 
                 4.49 
                 3.74 
                 9.67 
                 5.32 
                 2.74 
               
               
                 OR Quartile 3 
                 3.26 
                 2.28 
                 3.14 
                 2.05 
                 1.87 
                 2.66 
                 0.974 
                 1.52 
                 2.13 
               
               
                 p Value 
                 0.16 
                 0.082 
                 0.11 
                 0.42 
                 0.19 
                 0.18 
                 0.98 
                 0.38 
                 0.31 
               
               
                 Lower limit of 95% CI 
                 0.616 
                 0.901 
                 0.760 
                 0.355 
                 0.736 
                 0.628 
                 0.131 
                 0.594 
                 0.489 
               
               
                 Upper limit of 95% CI 
                 17.2 
                 5.75 
                 13.0 
                 11.9 
                 4.74 
                 11.2 
                 7.27 
                 3.90 
                 9.26 
               
               
                 OR Quartile 4 
                 6.51 
                 7.64 
                 3.86 
                 4.80 
                 6.69 
                 3.40 
                 3.21 
                 5.84 
                 2.89 
               
               
                 p Value 
                 0.20 
                 0.0099 
                 0.21 
                 0.29 
                 0.016 
                 0.26 
                 0.44 
                 0.026 
                 0.33 
               
               
                 Lower limit of 95% CI 
                 0.359 
                 1.63 
                 0.459 
                 0.259 
                 1.42 
                 0.400 
                 0.165 
                 1.24 
                 0.337 
               
               
                 Upper limit of 95% CI 
                 118 
                 35.8 
                 32.5 
                 89.1 
                 31.4 
                 28.9 
                 62.2 
                 27.5 
                 24.9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.2 
               
             
            
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 24 hours after sample collection and renal status is assessed by  
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
            
           
           
               
               
            
               
                   
                 Recovery Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                   
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                   
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.545 
                 1.19 
                 1.04 
                 1.09 
                 1.05 
                 1.03 
               
               
                 Average 
                 0.882 
                 2.14 
                 1.06 
                 2.07 
                 1.17 
                 2.05 
               
               
                 Stdev 
                 0.714 
                 2.16 
                 0.765 
                 2.14 
                 0.748 
                 2.14 
               
               
                 p (t-test) 
                   
                 7.0E−4 
                   
                 0.015 
                   
                 0.042 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 2.75 
                 7.86 
                 2.75 
                 7.86 
                 2.75 
                 7.86 
               
               
                 n (Patient) 
                 11 
                 69 
                 8 
                 72 
                 7 
                 73 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.556 
                 1.60 
                 0.651 
                 1.48 
                 0.651 
                 1.48 
               
               
                 Average 
                 0.967 
                 2.61 
                 1.02 
                 2.48 
                 1.02 
                 2.48 
               
               
                 Stdev 
                 0.884 
                 2.34 
                 0.914 
                 2.32 
                 0.914 
                 2.32 
               
               
                 p (t-test) 
                   
                 4.3E−5 
                   
                 1.8E−4 
                   
                 1.8E−4 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
               
               
                 n (Patient) 
                 31 
                 49 
                 28 
                 52 
                 28 
                 52 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.04 
                 1.19 
                 1.05 
                 1.19 
                 1.11 
                 1.15 
               
               
                 Average 
                 1.34 
                 2.16 
                 1.42 
                 2.12 
                 1.51 
                 2.05 
               
               
                 Stdev 
                 1.21 
                 2.10 
                 1.22 
                 2.10 
                 1.22 
                 2.09 
               
               
                 p (t-test) 
                   
                 0.073 
                   
                 0.13 
                   
                 0.26 
               
               
                 Min 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
               
               
                 Max 
                 4.74 
                 6.66 
                 4.74 
                 6.66 
                 4.74 
                 6.66 
               
               
                 n (Patient) 
                 14 
                 54 
                 13 
                 55 
                 12 
                 57 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr  
                 sCr 
                 UO 
                 sCr  
                 sCr 
                 UO 
                 sCr  
                 sCr 
                 UO 
               
               
                   
                 or UO 
                 only 
                 only 
                 or UO 
                 only 
                 only 
                 or UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.67 
                 0.72 
                 0.59 
                 0.60 
                 0.69 
                 0.55 
                 0.54 
                 0.69 
                 0.50 
               
               
                 SE 
                 0.080 
                 0.057 
                 0.083 
                 0.10 
                 0.060 
                 0.087 
                 0.11 
                 0.060 
                 0.092 
               
               
                 p Value 
                 0.036 
                 1.5E−4 
                 0.29 
                 0.33 
                 0.0019 
                 0.58 
                 0.71 
                 0.0019 
                 1.0 
               
               
                 nCohort Recovered 
                 11 
                 31 
                 14 
                 8 
                 28 
                 13 
                 7 
                 28 
                 12 
               
               
                 nCohort Non-recovered 
                 69 
                 49 
                 54 
                 72 
                 52 
                 55 
                 73 
                 52 
                 57 
               
               
                 Cutoff Quartile 2 
                 0.457 
                 0.457 
                 0.525 
                 0.457 
                 0.457 
                 0.502 
                 0.457 
                 0.457 
                 0.474 
               
               
                 Sensitivity 
                  77% 
                 82% 
                 76% 
                  75% 
                 81% 
                 73% 
                  74% 
                 81% 
                 70% 
               
               
                 Specificity 
                  36% 
                 35% 
                 29% 
                  25% 
                 36% 
                 15% 
                  14% 
                 36% 
                  8% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
               
               
                 Sensitivity 
                  52% 
                 59% 
                 52% 
                  50% 
                 56% 
                 51% 
                  49% 
                 56% 
                 49% 
               
               
                 Specificity 
                  64% 
                 65% 
                 57% 
                  50% 
                 61% 
                 54% 
                  43% 
                 61% 
                 50% 
               
               
                 Cutoff Quartile 4 
                 2.88 
                 2.88 
                 2.94 
                 2.88 
                 2.88 
                 2.94 
                 2.88 
                 2.88 
                 2.91 
               
               
                 Sensitivity 
                  29% 
                 37% 
                 30% 
                  28% 
                 35% 
                 29% 
                  27% 
                 35% 
                 28% 
               
               
                 Specificity 
                 100% 
                 94% 
                 93% 
                 100% 
                 93% 
                 92% 
                 100% 
                 93% 
                 92% 
               
               
                 OR Quartile 2 
                 1.89 
                 2.44 
                 1.26 
                 1.00 
                 2.33 
                 0.485 
                 0.474 
                 2.33 
                 0.214 
               
               
                 p Value 
                 0.35 
                 0.089 
                 0.73 
                 1.0 
                 0.11 
                 0.38 
                 0.50 
                 0.11 
                 0.15 
               
               
                 Lower limit of 95% CI 
                 0.491 
                 0.871 
                 0.338 
                 0.185 
                 0.828 
                 0.0960 
                 0.0535 
                 0.828 
                 0.0256 
               
               
                 Upper limit of 95% CI 
                 7.30 
                 6.86 
                 4.71 
                 5.40 
                 6.57 
                 2.45 
                 4.19 
                 6.57 
                 1.79 
               
               
                 OR Quartile 3 
                 1.91 
                 2.64 
                 1.44 
                 1.00 
                 1.95 
                 1.21 
                 0.730 
                 1.95 
                 0.966 
               
               
                 p Value 
                 0.34 
                 0.041 
                 0.55 
                 1.0 
                 0.16 
                 0.76 
                 0.69 
                 0.16 
                 0.96 
               
               
                 Lower limit of 95% CI 
                 0.512 
                 1.04 
                 0.439 
                 0.232 
                 0.765 
                 0.360 
                 0.152 
                 0.765 
                 0.278 
               
               
                 Upper limit of 95% CI 
                 7.12 
                 6.69 
                 4.70 
                 4.31 
                 4.96 
                 4.06 
                 3.49 
                 4.96 
                 3.35 
               
               
                 OR Quartile 4 
                 9.53 
                 8.42 
                 5.47 
                 6.64 
                 6.88 
                 4.92 
                 5.75 
                 6.88 
                 4.29 
               
               
                 p Value 
                 0.12 
                 0.0069 
                 0.12 
                 0.20 
                 0.015 
                 0.14 
                 0.24 
                 0.015 
                 0.18 
               
               
                 Lower limit of 95% CI 
                 0.536 
                 1.79 
                 0.660 
                 0.366 
                 1.46 
                 0.590 
                 0.314 
                 1.46 
                 0.512 
               
               
                 Upper limit of 95% CI 
                 169 
                 39.5 
                 45.4 
                 120 
                 32.3 
                 41.1 
                 105 
                 32.3 
                 36.0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.04 
                 1.19 
                 1.05 
                 1.03 
                 1.05 
                 1.03 
               
               
                 Average 
                 1.18 
                 2.29 
                 1.27 
                 2.22 
                 1.27 
                 2.22 
               
               
                 Stdev 
                 0.991 
                 2.30 
                 0.993 
                 2.29 
                 0.993 
                 2.29 
               
               
                 p (t-test) 
                   
                 0.0038 
                   
                 0.012 
                   
                 0.012 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
               
               
                 n (Patient) 
                 23 
                 57 
                 21 
                 59 
                 21 
                 59 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.653 
                 1.58 
                 0.640 
                 1.48 
                 0.640 
                 1.48 
               
               
                 Average 
                 1.17 
                 2.50 
                 1.16 
                 2.47 
                 1.16 
                 2.47 
               
               
                 Stdev 
                 1.27 
                 2.32 
                 1.29 
                 2.30 
                 1.29 
                 2.30 
               
               
                 p (t-test) 
                   
                 0.0020 
                   
                 0.0022 
                   
                 0.0022 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 6.43 
                 7.86 
                 6.43 
                 7.86 
                 6.43 
                 7.86 
               
               
                 n (Patient) 
                 34 
                 45 
                 33 
                 46 
                 33 
                 46 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.10 
                 1.33 
                 1.24 
                 1.19 
                 1.24 
                 1.19 
               
               
                 Average 
                 1.47 
                 2.48 
                 1.58 
                 2.32 
                 1.58 
                 2.32 
               
               
                 Stdev 
                 1.23 
                 2.32 
                 1.24 
                 2.30 
                 1.24 
                 2.30 
               
               
                 p (t-test) 
                   
                 0.036 
                   
                 0.12 
                   
                 0.12 
               
               
                 Min 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
               
               
                 Max 
                 4.74 
                 6.66 
                 4.74 
                 6.66 
                 4.74 
                 6.66 
               
               
                 n (Patient) 
                 22 
                 37 
                 20 
                 40 
                 20 
                 40 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                 sCr  
                 UO 
                 sCr or 
                 sCr  
                 UO 
                 sCr or 
                 sCr  
                 UO 
               
               
                 Duration (hr) 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.61 
                 0.68 
                 0.58 
                 0.56 
                 0.69 
                 0.52 
                 0.56 
                 0.69 
                 0.52 
               
               
                 SE 
                 0.067 
                 0.060 
                 0.076 
                 0.072 
                 0.059 
                 0.079 
                 0.072 
                 0.059 
                 0.079 
               
               
                 p Value 
                 0.099 
                 0.0028 
                 0.29 
                 0.38 
                 0.0018 
                 0.80 
                 0.38 
                 0.0018 
                 0.80 
               
               
                 nCohort  
                 23 
                 34 
                 22 
                 21 
                 33 
                 20 
                 21 
                 33 
                 20 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Non- 
                 57 
                 45 
                 37 
                 59 
                 46 
                 40 
                 59 
                 46 
                 40 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.457 
                 0.454 
                 0.520 
                 0.457 
                 0.454 
                 0.502 
                 0.457 
                 0.454 
                 0.502 
               
               
                 Sensitivity 
                 75% 
                 82% 
                 73% 
                 73% 
                 83% 
                 68% 
                 73% 
                 83% 
                 68% 
               
               
                 Specificity 
                 26% 
                 35% 
                 23% 
                 19% 
                 36% 
                 10% 
                 19% 
                 36% 
                 10% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.20 
                 1.04 
                 1.04 
                 1.19 
                 1.04 
                 1.04 
                 1.19 
               
               
                 Sensitivity 
                 51% 
                 56% 
                 51% 
                 49% 
                 57% 
                 50% 
                 49% 
                 57% 
                 50% 
               
               
                 Specificity 
                 52% 
                 59% 
                 55% 
                 48% 
                 61% 
                 50% 
                 48% 
                 61% 
                 50% 
               
               
                 Cutoff Quartile 4 
                 2.88 
                 2.82 
                 2.98 
                 2.88 
                 2.82 
                 2.94 
                 2.88 
                 2.82 
                 2.94 
               
               
                 Sensitivity 
                 32% 
                 38% 
                 32% 
                 31% 
                 37% 
                 30% 
                 31% 
                 37% 
                 30% 
               
               
                 Specificity 
                 91% 
                 91% 
                 86% 
                 90% 
                 91% 
                 85% 
                 90% 
                 91% 
                 85% 
               
               
                 OR Quartile 2 
                 1.08 
                 2.52 
                 0.794 
                 0.632 
                 2.71 
                 0.231 
                 0.632 
                 2.71 
                 0.231 
               
               
                 p Value 
                 0.89 
                 0.081 
                 0.71 
                 0.47 
                 0.060 
                 0.073 
                 0.47 
                 0.060 
                 0.073 
               
               
                 Lower limit of 
                 0.358 
                 0.893 
                 0.231 
                 0.185 
                 0.958 
                 0.0464 
                 0.185 
                 0.958 
                 0.0464 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 3.29 
                 7.13 
                 2.73 
                 2.17 
                 7.69 
                 1.15 
                 2.17 
                 7.69 
                 1.15 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.13 
                 1.79 
                 1.27 
                 0.879 
                 2.00 
                 1.00 
                 0.879 
                 2.00 
                 1.00 
               
               
                 p Value 
                 0.80 
                 0.21 
                 0.66 
                 0.80 
                 0.14 
                 1.0 
                 0.80 
                 0.14 
                 1.0 
               
               
                 Lower limit of  
                 0.429 
                 0.725 
                 0.440 
                 0.324 
                 0.805 
                 0.342 
                 0.324 
                 0.805 
                 0.342 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 2.98 
                 4.40 
                 3.65 
                 2.38 
                 4.97 
                 2.93 
                 2.38 
                 4.97 
                 2.93 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 4.85 
                 6.27 
                 3.04 
                 4.17 
                 5.86 
                 2.43 
                 4.17 
                 5.86 
                 2.43 
               
               
                 p Value 
                 0.047 
                 0.0068 
                 0.12 
                 0.073 
                 0.0091 
                 0.21 
                 0.073 
                 0.0091 
                 0.21 
               
               
                 Lower limit of 
                 1.02 
                 1.66 
                 0.751 
                 0.877 
                 1.55 
                 0.598 
                 0.877 
                 1.55 
                 0.598 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 22.9 
                 23.7 
                 12.3 
                 19.8 
                 22.1 
                 9.86 
                 19.8 
                 22.1 
                 9.86 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.838 
                 1.19 
                 1.04 
                 1.11 
                 1.04 
                 1.11 
               
               
                 Average 
                 1.11 
                 2.37 
                 1.14 
                 2.33 
                 1.14 
                 2.33 
               
               
                 Stdev 
                 0.912 
                 2.35 
                 0.915 
                 2.34 
                 0.915 
                 2.34 
               
               
                 p (t-test) 
                   
                 0.0012 
                   
                 0.0020 
                   
                 0.0020 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
                 3.52 
                 7.86 
               
               
                 n (Patient) 
                 26 
                 53 
                 25 
                 54 
                 25 
                 54 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.665 
                 1.19 
                 0.653 
                 1.20 
                 0.848 
                 1.19 
               
               
                 Average 
                 1.36 
                 2.33 
                 1.25 
                 2.40 
                 1.31 
                 2.31 
               
               
                 Stdev 
                 1.58 
                 2.29 
                 1.46 
                 2.31 
                 1.49 
                 2.30 
               
               
                 p (t-test) 
                   
                 0.034 
                   
                 0.010 
                   
                 0.025 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 6.43 
                 7.86 
                 6.43 
                 7.86 
                 6.43 
                 7.86 
               
               
                 n (Patient) 
                 35 
                 42 
                 34 
                 43 
                 32 
                 45 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.05 
                 1.33 
                 1.10 
                 1.26 
                 1.10 
                 1.26 
               
               
                 Average 
                 1.80 
                 2.43 
                 1.89 
                 2.38 
                 1.89 
                 2.38 
               
               
                 Stdev 
                 1.74 
                 2.27 
                 1.75 
                 2.26 
                 1.75 
                 2.26 
               
               
                 p (t-test) 
                   
                 0.28 
                   
                 0.42 
                   
                 0.42 
               
               
                 Min 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
               
               
                 Max 
                 6.26 
                 6.66 
                 6.26 
                 6.66 
                 6.26 
                 6.66 
               
               
                 n (Patient) 
                 17 
                 35 
                 16 
                 36 
                 16 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.63 
                 0.64 
                 0.57 
                 0.61 
                 0.66 
                 0.53 
                 0.61 
                 0.62 
                 0.53 
               
               
                 SE 
                 0.064 
                 0.063 
                 0.084 
                 0.066 
                 0.062 
                 0.087 
                 0.066 
                 0.064 
                 0.087 
               
               
                 p Value 
                 0.038 
                 0.025 
                 0.43 
                 0.089 
                 0.0091 
                 0.70 
                 0.089 
                 0.055 
                 0.70 
               
               
                 nCohort Recovered 
                 26 
                 35 
                 17 
                 25 
                 34 
                 16 
                 25 
                 32 
                 16 
               
               
                 nCohort Non- 
                 53 
                 42 
                 35 
                 54 
                 43 
                 36 
                 54 
                 45 
                 36 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.454 
                 0.448 
                 0.525 
                 0.454 
                 0.448 
                 0.525 
                 0.454 
                 0.448 
                 0.525 
               
               
                 Sensitivity 
                 77% 
                 81% 
                 74% 
                 76% 
                 81% 
                 72% 
                 76% 
                 78% 
                 72% 
               
               
                 Specificity 
                 31% 
                 34% 
                 24% 
                 28% 
                 35% 
                 19% 
                 28% 
                 31% 
                 19% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.03 
                 1.19 
                 1.04 
                 1.03 
                 1.19 
                 1.04 
                 1.03 
                 1.19 
               
               
                 Sensitivity 
                 51% 
                 52% 
                 54% 
                 50% 
                 53% 
                 53% 
                 50% 
                 51% 
                 53% 
               
               
                 Specificity 
                 54% 
                 54% 
                 59% 
                 52% 
                 56% 
                 56% 
                 52% 
                 53% 
                 56% 
               
               
                 Cutoff Quartile 4 
                 2.82 
                 2.75 
                 3.17 
                 2.82 
                 2.75 
                 3.17 
                 2.82 
                 2.75 
                 3.17 
               
               
                 Sensitivity 
                 34% 
                 36% 
                 26% 
                 33% 
                 37% 
                 25% 
                 33% 
                 36% 
                 25% 
               
               
                 Specificity 
                 92% 
                 89% 
                 76% 
                 92% 
                 91% 
                 75% 
                 92% 
                 91% 
                 75% 
               
               
                 OR Quartile 2 
                 1.52 
                 2.22 
                 0.889 
                 1.23 
                 2.39 
                 0.600 
                 1.23 
                 1.59 
                 0.600 
               
               
                 p Value 
                 0.44 
                 0.13 
                 0.86 
                 0.71 
                 0.10 
                 0.49 
                 0.71 
                 0.38 
                 0.49 
               
               
                 Lower limit of  
                 0.530 
                 0.784 
                 0.230 
                 0.419 
                 0.842 
                 0.140 
                 0.419 
                 0.570 
                 0.140 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 4.35 
                 6.27 
                 3.44 
                 3.59 
                 6.76 
                 2.56 
                 3.59 
                 4.44 
                 2.56 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.21 
                 1.31 
                 1.70 
                 1.08 
                 1.46 
                 1.44 
                 1.08 
                 1.18 
                 1.44 
               
               
                 p Value 
                 0.69 
                 0.56 
                 0.38 
                 0.87 
                 0.41 
                 0.55 
                 0.87 
                 0.71 
                 0.55 
               
               
                 Lower limit of  
                 0.473 
                 0.531 
                 0.525 
                 0.419 
                 0.590 
                 0.439 
                 0.419 
                 0.478 
                 0.439 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 3.10 
                 3.21 
                 5.48 
                 2.80 
                 3.60 
                 4.70 
                 2.80 
                 2.94 
                 4.70 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 6.17 
                 4.31 
                 1.12 
                 5.75 
                 6.12 
                 1.00 
                 5.75 
                 5.33 
                 1.00 
               
               
                 p Value 
                 0.021 
                 0.019 
                 0.86 
                 0.027 
                 0.0079 
                 1.0 
                 0.027 
                 0.014 
                 1.0 
               
               
                 Lower limit of  
                 1.31 
                 1.27 
                 0.291 
                 1.22 
                 1.61 
                 0.257 
                 1.22 
                 1.40 
                 0.257 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 29.1 
                 14.5 
                 4.35 
                 27.1 
                 23.3 
                 3.90 
                 27.1 
                 20.3 
                 3.90 
               
               
                 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 within 7 days after sample collection and renal status is assessed by serum creatinine 
               
               
                 (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.620 
                 1.26 
                 0.637 
                 1.19 
                 0.640 
                 1.16 
               
               
                 Average 
                 1.44 
                 2.41 
                 1.43 
                 2.33 
                 1.49 
                 2.25 
               
               
                 Stdev 
                 1.70 
                 2.24 
                 1.68 
                 2.22 
                 1.71 
                 2.21 
               
               
                 p (t-test) 
                   
                 0.030 
                   
                 0.040 
                   
                 0.085 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 41 
                 42 
                 37 
                 46 
                 35 
                 48 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.848 
                 1.20 
                 0.848 
                 1.20 
                 1.03 
                 1.19 
               
               
                 Average 
                 1.66 
                 2.37 
                 1.62 
                 2.38 
                 1.71 
                 2.21 
               
               
                 Stdev 
                 1.88 
                 2.24 
                 1.86 
                 2.24 
                 1.92 
                 2.18 
               
               
                 p (t-test) 
                   
                 0.15 
                   
                 0.11 
                   
                 0.29 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 48 
                 33 
                 46 
                 35 
                 42 
                 39 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.04 
                 1.08 
                 1.04 
                 1.08 
                 1.04 
                 1.03 
               
               
                 Average 
                 1.86 
                 2.01 
                 1.60 
                 2.10 
                 1.65 
                 2.07 
               
               
                 Stdev 
                 2.29 
                 2.00 
                 1.84 
                 2.09 
                 1.85 
                 2.09 
               
               
                 p (t-test) 
                   
                 0.77 
                   
                 0.27 
                   
                 0.36 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 8.44 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 31 
                 48 
                 31 
                 48 
                 30 
                 49 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or  
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.66 
                 0.62 
                 0.55 
                 0.64 
                 0.62 
                 0.57 
                 0.60 
                 0.58 
                 0.55 
               
               
                 SE 
                 0.060 
                 0.064 
                 0.066 
                 0.061 
                 0.064 
                 0.065 
                 0.062 
                 0.064 
                 0.066 
               
               
                 p Value 
                 0.0088 
                 0.070 
                 0.42 
                 0.023 
                 0.070 
                 0.26 
                 0.100 
                 0.20 
                 0.44 
               
               
                 nCohort Recovered 
                 41 
                 48 
                 31 
                 37 
                 46 
                 31 
                 35 
                 42 
                 30 
               
               
                 nCohort Non- 
                 42 
                 33 
                 48 
                 46 
                 35 
                 48 
                 48 
                 39 
                 49 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.467 
                 0.460 
                 0.493 
                 0.467 
                 0.460 
                 0.493 
                 0.467 
                 0.460 
                 0.493 
               
               
                 Sensitivity 
                 81% 
                 79% 
                 77% 
                 80% 
                 77% 
                 77% 
                 77% 
                 77% 
                 76% 
               
               
                 Specificity 
                 32% 
                 29% 
                 29% 
                 32% 
                 28% 
                 29% 
                 29% 
                 29% 
                 27% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
               
               
                 Sensitivity 
                 57% 
                 55% 
                 50% 
                 54% 
                 54% 
                 50% 
                 52% 
                 51% 
                 49% 
               
               
                 Specificity 
                 59% 
                 54% 
                 52% 
                 57% 
                 54% 
                 52% 
                 54% 
                 52% 
                 50% 
               
               
                 Cutoff Quartile 4 
                 2.82 
                 2.87 
                 2.82 
                 2.82 
                 2.87 
                 2.82 
                 2.82 
                 2.87 
                 2.82 
               
               
                 Sensitivity 
                 33% 
                 30% 
                 27% 
                 33% 
                 31% 
                 29% 
                 31% 
                 28% 
                 29% 
               
               
                 Specificity 
                 83% 
                 79% 
                 77% 
                 84% 
                 80% 
                 81% 
                 83% 
                 79% 
                 80% 
               
               
                 OR Quartile 2 
                 1.97 
                 1.53 
                 1.38 
                 1.97 
                 1.33 
                 1.38 
                 1.35 
                 1.33 
                 1.12 
               
               
                 p Value 
                 0.19 
                 0.42 
                 0.54 
                 0.18 
                 0.58 
                 0.54 
                 0.56 
                 0.57 
                 0.83 
               
               
                 Lower limit of  
                 0.717 
                 0.540 
                 0.493 
                 0.724 
                 0.481 
                 0.493 
                 0.497 
                 0.490 
                 0.397 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 5.43 
                 4.33 
                 3.84 
                 5.38 
                 3.68 
                 3.84 
                 3.64 
                 3.63 
                 3.17 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.88 
                 1.42 
                 1.07 
                 1.56 
                 1.41 
                 1.07 
                 1.29 
                 1.16 
                 0.960 
               
               
                 p Value 
                 0.15 
                 0.44 
                 0.89 
                 0.32 
                 0.44 
                 0.89 
                 0.57 
                 0.74 
                 0.93 
               
               
                 Lower limit of  
                 0.787 
                 0.582 
                 0.432 
                 0.654 
                 0.585 
                 0.432 
                 0.539 
                 0.484 
                 0.387 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 4.50 
                 3.45 
                 2.63 
                 3.74 
                 3.42 
                 2.63 
                 3.09 
                 2.77 
                 2.38 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 2.43 
                 1.65 
                 1.27 
                 2.50 
                 1.88 
                 1.72 
                 2.20 
                 1.44 
                 1.60 
               
               
                 p Value 
                 0.093 
                 0.33 
                 0.65 
                 0.093 
                 0.22 
                 0.33 
                 0.15 
                 0.48 
                 0.40 
               
               
                 Lower limit of  
                 0.862 
                 0.597 
                 0.443 
                 0.858 
                 0.680 
                 0.579 
                 0.753 
                 0.522 
                 0.539 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 6.84 
                 4.57 
                 3.66 
                 7.29 
                 5.22 
                 5.09 
                 6.41 
                 3.97 
                 4.75 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 125 
                 258 
                 108 
                 255 
                 111 
                 254 
               
               
                 Average 
                 149 
                 277 
                 107 
                 275 
                 116 
                 272 
               
               
                 Stdev 
                 59.3 
                 120 
                 20.2 
                 119 
                 12.5 
                 120 
               
               
                 p (t-test) 
                   
                 2.9E−4 
                   
                 1.8E−10 
                   
                 6.9E−13 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 105 
                 73.7 
               
               
                 Max 
                 255 
                 651 
                 137 
                 651 
                 137 
                 651 
               
               
                 n (Patient) 
                 8 
                 74 
                 5 
                 77 
                 4 
                 78 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 182 
                 285 
                 182 
                 283 
                 171 
                 283 
               
               
                 Average 
                 206 
                 301 
                 205 
                 298 
                 201 
                 297 
               
               
                 Stdev 
                 89.8 
                 126 
                 92.3 
                 125 
                 93.2 
                 123 
               
               
                 p (t-test) 
                   
                 1.9E−4 
                   
                 3.3E−4 
                   
                 2.8E−4 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 446 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                 31 
                 50 
                 29 
                 52 
                 27 
                 54 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 243 
                 253 
                 265 
                 251 
                 289 
                 249 
               
               
                 Average 
                 232 
                 278 
                 233 
                 277 
                 253 
                 273 
               
               
                 Stdev 
                 112 
                 125 
                 118 
                 124 
                 110 
                 125 
               
               
                 p (t-test) 
                   
                 0.28 
                   
                 0.35 
                   
                 0.66 
               
               
                 Min 
                 73.7 
                 110 
                 73.7 
                 110 
                 108 
                 73.7 
               
               
                 Max 
                 395 
                 651 
                 395 
                 651 
                 395 
                 651 
               
               
                 n (Patient) 
                 10 
                 61 
                 9 
                 62 
                 8 
                 64 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.84 
                 0.73 
                 0.59 
                 0.97 
                 0.73 
                 0.59 
                 0.95 
                 0.74 
                 0.53 
               
               
                 SE 
                 0.057 
                 0.055 
                 0.093 
                 0.021 
                 0.056 
                 0.097 
                 0.033 
                 0.055 
                 0.11 
               
               
                 p Value 
                 2.6E−9 
                 2.9E−5 
                 0.31 
                 0 
                 4.3E−5 
                 0.35 
                 0 
                 1.4E−5 
                 0.78 
               
               
                 nCohort Recovered 
                 8 
                 31 
                 10 
                 5 
                 29 
                 9 
                 4 
                 27 
                 8 
               
               
                 nCohort Non-recovered 
                 74 
                 50 
                 61 
                 77 
                 52 
                 62 
                 78 
                 54 
                 64 
               
               
                 Cutoff Quartile 2 
                 172 
                 171 
                 174 
                 172 
                 171 
                 174 
                 172 
                 171 
                 175 
               
               
                 Sensitivity 
                  78% 
                 86% 
                 77% 
                  79% 
                 87% 
                 77% 
                  78% 
                 87% 
                 77% 
               
               
                 Specificity 
                  62% 
                 45% 
                 40% 
                 100% 
                 48% 
                 44% 
                 100% 
                 52% 
                 38% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 253 
                 249 
                 249 
                 253 
                 249 
                 249 
                 251 
               
               
                 Sensitivity 
                  54% 
                 62% 
                 49% 
                 53% 
                 62% 
                 48% 
                  53% 
                 61% 
                 48% 
               
               
                 Specificity 
                  88% 
                 71% 
                 50% 
                 100% 
                 72% 
                 44% 
                 100% 
                 74% 
                 38% 
               
               
                 Cutoff Quartile 4 
                 331 
                 331 
                 339 
                 331 
                 331 
                 339 
                 331 
                 331 
                 337 
               
               
                 Sensitivity 
                  28% 
                 34% 
                 26% 
                  27% 
                 33% 
                 26% 
                  27% 
                 31% 
                 25% 
               
               
                 Specificity 
                 100% 
                 90% 
                 80% 
                 100% 
                 90% 
                 78% 
                 100% 
                 89% 
                 75% 
               
               
                 OR Quartile 2 
                 6.04 
                 5.06 
                 2.24 
                 41.0 
                 6.00 
                 2.74 
                 31.6 
                 7.23 
                 1.96 
               
               
                 p Value 
                 0.022 
                 0.0029 
                 0.26 
                 0.013 
                 0.0011 
                 0.17 
                 0.023 
                 4.0E-4 
                 0.39 
               
               
                 Lower limit of 95% CI 
                 1.30 
                 1.74 
                 0.553 
                 2.16 
                 2.04 
                 0.648 
                 1.62 
                 2.42 
                 0.419 
               
               
                 Upper limit of 95% CI 
                 28.0 
                 14.7 
                 9.07 
                 780 
                 17.7 
                 11.6 
                 616 
                 21.6 
                 9.18 
               
               
                 OR Quartile 3 
                 8.24 
                 3.99 
                 0.968 
                 12.5 
                 4.20 
                 0.750 
                 9.96 
                 4.49 
                 0.564 
               
               
                 p Value 
                 0.054 
                 0.0049 
                 0.96 
                 0.091 
                 0.0044 
                 0.69 
                 0.13 
                 0.0039 
                 0.46 
               
               
                 Lower limit of 95% CI 
                 0.964 
                 1.52 
                 0.254 
                 0.668 
                 1.56 
                 0.184 
                 0.519 
                 1.62 
                 0.124 
               
               
                 Upper limit of 95% CI 
                 70.3 
                 10.4 
                 3.69 
                 234 
                 11.3 
                 3.06 
                 191 
                 12.5 
                 2.56 
               
               
                 OR Quartile 4 
                 6.83 
                 4.81 
                 1.42 
                 4.19 
                 4.21 
                 1.22 
                 3.37 
                 3.68 
                 1.00 
               
               
                 p Value 
                 0.19 
                 0.020 
                 0.68 
                 0.34 
                 0.034 
                 0.82 
                 0.42 
                 0.055 
                 1.0 
               
               
                 Lower limit of 95% CI 
                 0.377 
                 1.28 
                 0.273 
                 0.222 
                 1.12 
                 0.229 
                 0.174 
                 0.972 
                 0.183 
               
               
                 Upper limit of 95% CI 
                 124 
                 18.1 
                 7.41 
                 79.0 
                 15.9 
                 6.48 
                 65.2 
                 13.9 
                 5.46 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 179 
                 255 
                 132 
                 254 
                 132 
                 254 
               
               
                 Average 
                 196 
                 279 
                 186 
                 278 
                 183 
                 276 
               
               
                 Stdev 
                 90.2 
                 121 
                 97.7 
                 119 
                 88.7 
                 120 
               
               
                 p (t-test) 
                   
                 0.027 
                   
                 0.044 
                   
                 0.068 
               
               
                 Min 
                 73.7 
                 103 
                 73.7 
                 103 
                 108 
                 73.7 
               
               
                 Max 
                 329 
                 651 
                 329 
                 651 
                 329 
                 651 
               
               
                 n (Patient) 
                 10 
                 70 
                 8 
                 72 
                 6 
                 74 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 204 
                 293 
                 193 
                 283 
                 187 
                 285 
               
               
                 Average 
                 213 
                 306 
                 211 
                 303 
                 208 
                 303 
               
               
                 Stdev 
                 88.7 
                 126 
                 91.4 
                 124 
                 90.8 
                 123 
               
               
                 p (t-test) 
                   
                 2.9E−4 
                   
                 4.5E−4 
                   
                 2.6E−4 
               
               
                 Min 
                 73.7 
                 103 
                 73.7 
                 103 
                 73.7 
                 103 
               
               
                 Max 
                 446 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                 31 
                 48 
                 29 
                 50 
                 28 
                 51 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 314 
                 239 
                 321 
                 235 
                 328 
                 235 
               
               
                 Average 
                 265 
                 275 
                 268 
                 273 
                 283 
                 270 
               
               
                 Stdev 
                 102 
                 129 
                 105 
                 129 
                 93.9 
                 129 
               
               
                 p (t-test) 
                   
                 0.76 
                   
                 0.87 
                   
                 0.69 
               
               
                 Min 
                 73.7 
                 110 
                 73.7 
                 110 
                 108 
                 73.7 
               
               
                 Max 
                 395 
                 651 
                 395 
                 651 
                 395 
                 651 
               
               
                 n (Patient) 
                 15 
                 54 
                 14 
                 55 
                 13 
                 57 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.70 
                 0.72 
                 0.48 
                 0.73 
                 0.72 
                 0.47 
                 0.75 
                 0.74 
                 0.41 
               
               
                 SE 
                 0.079 
                 0.057 
                 0.084 
                 0.081 
                 0.057 
                 0.086 
                 0.088 
                 0.056 
                 0.085 
               
               
                 p Value 
                 0.013 
                 8.0E−5 
                 0.77 
                 0.0046 
                 1.0E−4 
                 0.69 
                 0.0051 
                 2.4E−5 
                 0.31 
               
               
                 nCohort Recovered 
                 10 
                 31 
                 15 
                 8 
                 29 
                 14 
                 6 
                 28 
                 13 
               
               
                 nCohort Non- 
                 70 
                 48 
                 54 
                 72 
                 50 
                 55 
                 74 
                 51 
                 57 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 176 
                 175 
                 177 
                 176 
                 175 
                 177 
                 176 
                 175 
                 178 
               
               
                 Sensitivity 
                  79% 
                 85% 
                 74% 
                  79% 
                 86% 
                 75% 
                  78% 
                 86% 
                 74% 
               
               
                 Specificity 
                  50% 
                 42% 
                 27% 
                  62% 
                 45% 
                 29% 
                  67% 
                 46% 
                 23% 
               
               
                 Cutoff Quartile 3 
                 251 
                 249 
                 253 
                 251 
                 249 
                 253 
                 251 
                 249 
                 251 
               
               
                 Sensitivity 
                  51% 
                 60% 
                 44% 
                  51% 
                 60% 
                 44% 
                  51% 
                 61% 
                 44% 
               
               
                 Specificity 
                  60% 
                 68% 
                 33% 
                  62% 
                 69% 
                 29% 
                  67% 
                 71% 
                 23% 
               
               
                 Cutoff Quartile 4 
                 332 
                 333 
                 335 
                 332 
                 333 
                 335 
                 332 
                 333 
                 334 
               
               
                 Sensitivity 
                  29% 
                 35% 
                 26% 
                  28% 
                 34% 
                 25% 
                  27% 
                 33% 
                 25% 
               
               
                 Specificity 
                 100% 
                 90% 
                 80% 
                 100% 
                 90% 
                 79% 
                 100% 
                 89% 
                 69% 
               
               
                 OR Quartile 2 
                 3.67 
                 4.23 
                 1.04 
                 6.33 
                 4.99 
                 1.17 
                 7.25 
                 5.45 
                 0.840 
               
               
                 p Value 
                 0.062 
                 0.0084 
                 0.95 
                 0.019 
                 0.0036 
                 0.81 
                 0.030 
                 0.0023 
                 0.81 
               
               
                 Lower limit of  
                 0.937 
                 1.45 
                 0.284 
                 1.36 
                 1.69 
                 0.316 
                 1.22 
                 1.83 
                 0.203 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 14.4 
                 12.4 
                 3.80 
                 29.5 
                 14.7 
                 4.34 
                 43.2 
                 16.2 
                 3.47 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.59 
                 3.21 
                 0.400 
                 1.76 
                 3.33 
                 0.310 
                 2.11 
                 3.88 
                 0.234 
               
               
                 p Value 
                 0.50 
                 0.016 
                 0.13 
                 0.46 
                 0.015 
                 0.072 
                 0.40 
                 0.0076 
                 0.041 
               
               
                 Lower limit of  
                 0.412 
                 1.24 
                 0.120 
                 0.392 
                 1.26 
                 0.0864 
                 0.364 
                 1.43 
                 0.0582 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 6.12 
                 8.28 
                 1.33 
                 7.93 
                 8.78 
                 1.11 
                 12.2 
                 10.5 
                 0.943 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 8.52 
                 5.12 
                 1.40 
                 6.64 
                 4.46 
                 1.25 
                 4.89 
                 4.17 
                 0.733 
               
               
                 p Value 
                 0.15 
                 0.016 
                 0.64 
                 0.20 
                 0.028 
                 0.76 
                 0.29 
                 0.036 
                 0.64 
               
               
                 Lower limit of  
                 0.477 
                 1.35 
                 0.344 
                 0.366 
                 1.18 
                 0.305 
                 0.263 
                 1.10 
                 0.195 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 152 
                 19.3 
                 5.70 
                 120 
                 16.9 
                 5.15 
                 90.8 
                 15.8 
                 2.75 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 235 
                 256 
                 223 
                 255 
                 223 
                 255 
               
               
                 Average 
                 233 
                 283 
                 237 
                 280 
                 237 
                 280 
               
               
                 Stdev 
                 100 
                 127 
                 99.5 
                 127 
                 99.5 
                 127 
               
               
                 p (t-test) 
                   
                 0.082 
                   
                 0.15 
                   
                 0.15 
               
               
                 Min 
                 73.7 
                 103 
                 108 
                 73.7 
                 108 
                 73.7 
               
               
                 Max 
                 446 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                 21 
                 56 
                 18 
                 59 
                 18 
                 59 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 210 
                 283 
                 210 
                 285 
                 210 
                 285 
               
               
                 Average 
                 220 
                 305 
                 217 
                 305 
                 217 
                 305 
               
               
                 Stdev 
                 91.8 
                 131 
                 91.7 
                 129 
                 91.7 
                 129 
               
               
                 p (t-test) 
                   
                 0.0015 
                   
                 9.6E−4 
                   
                 9.6E−4 
               
               
                 Min 
                 73.7 
                 103 
                 73.7 
                 103 
                 73.7 
                 103 
               
               
                 Max 
                 446 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                 32 
                 44 
                 31 
                 45 
                 31 
                 45 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 301 
                 231 
                 320 
                 227 
                 320 
                 227 
               
               
                 Average 
                 280 
                 280 
                 296 
                 272 
                 296 
                 272 
               
               
                 Stdev 
                 89.4 
                 139 
                 77.1 
                 138 
                 77.1 
                 138 
               
               
                 p (t-test) 
                   
                 1.00 
                   
                 0.42 
                   
                 0.42 
               
               
                 Min 
                 73.7 
                 114 
                 108 
                 73.7 
                 108 
                 73.7 
               
               
                 Max 
                 429 
                 651 
                 429 
                 651 
                 429 
                 651 
               
               
                 n (Patient) 
                 20 
                 37 
                 18 
                 40 
                 18 
                 40 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.60 
                 0.69 
                 0.41 
                 0.59 
                 0.70 
                 0.35 
                 0.59 
                 0.70 
                 0.35 
               
               
                 SE 
                 0.070 
                 0.060 
                 0.078 
                 0.074 
                 0.059 
                 0.075 
                 0.074 
                 0.059 
                 0.075 
               
               
                 p Value 
                 0.16 
                 0.0015 
                 0.28 
                 0.24 
                 5.7E−4 
                 0.048 
                 0.24 
                 5.7E−4 
                 0.048 
               
               
                 nCohort Recovered 
                 21 
                 32 
                 20 
                 18 
                 31 
                 18 
                 18 
                 31 
                 18 
               
               
                 nCohort Non-recovered 
                 56 
                 44 
                 37 
                 59 
                 45 
                 40 
                 59 
                 45 
                 40 
               
               
                 Cutoff Quartile 2 
                 174 
                 173 
                 185 
                 174 
                 173 
                 187 
                 174 
                 173 
                 187 
               
               
                 Sensitivity 
                 79% 
                 86% 
                 68% 
                 78% 
                 87% 
                 68% 
                 78% 
                 87% 
                 68% 
               
               
                 Specificity 
                 38% 
                 41% 
                 15% 
                 39% 
                 42% 
                 11% 
                 39% 
                 42% 
                 11% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 257 
                 249 
                 249 
                 255 
                 249 
                 249 
                 255 
               
               
                 Sensitivity 
                 52% 
                 61% 
                 41% 
                 51% 
                 62% 
                 40% 
                 51% 
                 62% 
                 40% 
               
               
                 Specificity 
                 57% 
                 66% 
                 35% 
                 56% 
                 68% 
                 28% 
                 56% 
                 68% 
                 28% 
               
               
                 Cutoff Quartile 4 
                 335 
                 334 
                 335 
                 335 
                 334 
                 334 
                 335 
                 334 
                 334 
               
               
                 Sensitivity 
                 29% 
                 34% 
                 24% 
                 27% 
                 33% 
                 22% 
                 27% 
                 33% 
                 22% 
               
               
                 Specificity 
                 86% 
                 88% 
                 75% 
                 83% 
                 87% 
                 67% 
                 83% 
                 87% 
                 67% 
               
               
                 OR Quartile 2 
                 2.26 
                 4.33 
                 0.368 
                 2.25 
                 4.69 
                 0.260 
                 2.25 
                 4.69 
                 0.260 
               
               
                 p Value 
                 0.14 
                 0.0098 
                 0.16 
                 0.16 
                 0.0067 
                 0.10 
                 0.16 
                 0.0067 
                 0.10 
               
               
                 Lower limit of 95% CI 
                 0.760 
                 1.42 
                 0.0900 
                 0.727 
                 1.54 
                 0.0518 
                 0.727 
                 1.54 
                 0.0518 
               
               
                 Upper limit of 95% CI 
                 6.70 
                 13.2 
                 1.50 
                 6.97 
                 14.3 
                 1.30 
                 6.97 
                 14.3 
                 1.30 
               
               
                 OR Quartile 3 
                 1.43 
                 3.03 
                 0.367 
                 1.29 
                 3.46 
                 0.256 
                 1.29 
                 3.46 
                 0.256 
               
               
                 p Value 
                 0.49 
                 0.022 
                 0.082 
                 0.63 
                 0.012 
                 0.027 
                 0.63 
                 0.012 
                 0.027 
               
               
                 Lower limit of 95% CI 
                 0.521 
                 1.17 
                 0.119 
                 0.448 
                 1.32 
                 0.0765 
                 0.448 
                 1.32 
                 0.0765 
               
               
                 Upper limit of 95% CI 
                 3.94 
                 7.83 
                 1.14 
                 3.73 
                 9.07 
                 0.860 
                 3.73 
                 9.07 
                 0.860 
               
               
                 OR Quartile 4 
                 2.40 
                 3.62 
                 0.964 
                 1.86 
                 3.38 
                 0.581 
                 1.86 
                 3.38 
                 0.581 
               
               
                 p Value 
                 0.20 
                 0.039 
                 0.95 
                 0.37 
                 0.051 
                 0.39 
                 0.37 
                 0.051 
                 0.39 
               
               
                 Lower limit of 95% CI 
                 0.620 
                 1.07 
                 0.273 
                 0.475 
                 0.997 
                 0.170 
                 0.475 
                 0.997 
                 0.170 
               
               
                 Upper limit of 95% CI 
                 9.28 
                 12.3 
                 3.40 
                 7.29 
                 11.4 
                 1.99 
                 7.29 
                 11.4 
                 1.99 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 210 
                 267 
                 210 
                 267 
                 210 
                 267 
               
               
                 Average 
                 220 
                 289 
                 220 
                 289 
                 220 
                 289 
               
               
                 Stdev 
                 87.3 
                 129 
                 87.3 
                 129 
                 87.3 
                 129 
               
               
                 p (t-test) 
                   
                 0.011 
                   
                 0.011 
                   
                 0.011 
               
               
                 Min 
                 108 
                 73.7 
                 108 
                 73.7 
                 108 
                 73.7 
               
               
                 Max 
                 395 
                 651 
                 395 
                 651 
                 395 
                 651 
               
               
                 n (Patient) 
                 22 
                 52 
                 22 
                 52 
                 22 
                 52 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 221 
                 279 
                 211 
                 283 
                 211 
                 279 
               
               
                 Average 
                 238 
                 290 
                 228 
                 295 
                 230 
                 291 
               
               
                 Stdev 
                 119 
                 119 
                 112 
                 121 
                 115 
                 121 
               
               
                 p (t-test) 
                   
                 0.070 
                   
                 0.017 
                   
                 0.035 
               
               
                 Min 
                 73.7 
                 103 
                 73.7 
                 103 
                 73.7 
                 103 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 33 
                 40 
                 31 
                 42 
                 29 
                 44 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 308 
                 240 
                 308 
                 240 
                 308 
                 240 
               
               
                 Average 
                 287 
                 287 
                 287 
                 287 
                 287 
                 287 
               
               
                 Stdev 
                 72.0 
                 142 
                 72.0 
                 142 
                 72.0 
                 142 
               
               
                 p (t-test) 
                   
                 0.99 
                   
                 0.99 
                   
                 0.99 
               
               
                 Min 
                 140 
                 73.7 
                 140 
                 73.7 
                 140 
                 73.7 
               
               
                 Max 
                 395 
                 651 
                 395 
                 651 
                 395 
                 651 
               
               
                 n (Patient) 
                 14 
                 34 
                 14 
                 34 
                 14 
                 34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.65 
                 0.64 
                 0.41 
                 0.65 
                 0.67 
                 0.41 
                 0.65 
                 0.66 
                 0.41 
               
               
                 SE 
                 0.067 
                 0.064 
                 0.089 
                 0.067 
                 0.063 
                 0.089 
                 0.067 
                 0.064 
                 0.089 
               
               
                 p Value 
                 0.021 
                 0.031 
                 0.32 
                 0.021 
                 0.0055 
                 0.32 
                 0.021 
                 0.014 
                 0.32 
               
               
                 nCohort Recovered 
                 22 
                 33 
                 14 
                 22 
                 31 
                 14 
                 22 
                 29 
                 14 
               
               
                 nCohort Non-recovered 
                 52 
                 40 
                 34 
                 52 
                 42 
                 34 
                 52 
                 44 
                 34 
               
               
                 Cutoff Quartile 2 
                 175 
                 174 
                 201 
                 175 
                 174 
                 201 
                 175 
                 174 
                 201 
               
               
                 Sensitivity 
                 81% 
                 82% 
                 71% 
                 81% 
                 83% 
                 71% 
                 81% 
                 82% 
                 71% 
               
               
                 Specificity 
                 41% 
                 36% 
                 14% 
                 41% 
                 39% 
                 14% 
                 41% 
                 38% 
                 14% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 261 
                 249 
                 249 
                 261 
                 249 
                 249 
                 261 
               
               
                 Sensitivity 
                 56% 
                 57% 
                 41% 
                 56% 
                 60% 
                 41% 
                 56% 
                 57% 
                 41% 
               
               
                 Specificity 
                 64% 
                 61% 
                 29% 
                 64% 
                 65% 
                 29% 
                 64% 
                 62% 
                 29% 
               
               
                 Cutoff Quartile 4 
                 331 
                 329 
                 345 
                 331 
                 329 
                 345 
                 331 
                 329 
                 345 
               
               
                 Sensitivity 
                 29% 
                 30% 
                 26% 
                 29% 
                 31% 
                 26% 
                 29% 
                 30% 
                 26% 
               
               
                 Specificity 
                 82% 
                 82% 
                 79% 
                 82% 
                 84% 
                 79% 
                 82% 
                 83% 
                 79% 
               
               
                 OR Quartile 2 
                 2.91 
                 2.69 
                 0.400 
                 2.91 
                 3.16 
                 0.400 
                 2.91 
                 2.75 
                 0.400 
               
               
                 p Value 
                 0.056 
                 0.072 
                 0.28 
                 0.056 
                 0.038 
                 0.28 
                 0.056 
                 0.064 
                 0.28 
               
               
                 Lower limit of 95% CI 
                 0.973 
                 0.914 
                 0.0754 
                 0.973 
                 1.07 
                 0.0754 
                 0.973 
                 0.941 
                 0.0754 
               
               
                 Upper limit of 95% CI 
                 8.69 
                 7.94 
                 2.12 
                 8.69 
                 9.36 
                 2.12 
                 8.69 
                 8.03 
                 2.12 
               
               
                 OR Quartile 3 
                 2.21 
                 2.08 
                 0.280 
                 2.21 
                 2.67 
                 0.280 
                 2.21 
                 2.15 
                 0.280 
               
               
                 p Value 
                 0.13 
                 0.13 
                 0.064 
                 0.13 
                 0.045 
                 0.064 
                 0.13 
                 0.12 
                 0.064 
               
               
                 Lower limit of 95% CI 
                 0.790 
                 0.814 
                 0.0729 
                 0.790 
                 1.02 
                 0.0729 
                 0.790 
                 0.826 
                 0.0729 
               
               
                 Upper limit of 95% CI 
                 6.16 
                 5.32 
                 1.08 
                 6.16 
                 6.98 
                 1.08 
                 6.16 
                 5.61 
                 1.08 
               
               
                 OR Quartile 4 
                 1.82 
                 1.93 
                 1.32 
                 1.82 
                 2.33 
                 1.32 
                 1.82 
                 2.01 
                 1.32 
               
               
                 p Value 
                 0.34 
                 0.25 
                 0.71 
                 0.34 
                 0.15 
                 0.71 
                 0.34 
                 0.24 
                 0.71 
               
               
                 Lower limit of 95% CI 
                 0.529 
                 0.633 
                 0.298 
                 0.529 
                 0.731 
                 0.298 
                 0.529 
                 0.630 
                 0.298 
               
               
                 Upper limit of 95% CI 
                 6.29 
                 5.87 
                 5.84 
                 6.29 
                 7.43 
                 5.84 
                 6.29 
                 6.43 
                 5.84 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “recovered” and “non-recovered” cohorts where 
               
               
                 recovery starts within 7 days after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE 
               
               
                 criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 246 
                 255 
                 246 
                 255 
                 246 
                 252 
               
               
                 Average 
                 243 
                 292 
                 239 
                 290 
                 243 
                 285 
               
               
                 Stdev 
                 101 
                 141 
                 101 
                 137 
                 100 
                 138 
               
               
                 p (t-test) 
                   
                 0.076 
                   
                 0.055 
                   
                 0.11 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 103 
                 73.7 
               
               
                 Max 
                 446 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                 44 
                 40 
                 40 
                 44 
                 38 
                 46 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 246 
                 249 
                 246 
                 249 
                 239 
                 255 
               
               
                 Average 
                 254 
                 280 
                 254 
                 280 
                 246 
                 285 
               
               
                 Stdev 
                 121 
                 124 
                 122 
                 122 
                 119 
                 123 
               
               
                 p (t-test) 
                   
                 0.36 
                   
                 0.35 
                   
                 0.15 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 48 
                 33 
                 46 
                 35 
                 42 
                 39 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 273 
                 238 
                 265 
                 231 
                 273 
                 227 
               
               
                 Average 
                 266 
                 274 
                 259 
                 274 
                 265 
                 270 
               
               
                 Stdev 
                 105 
                 140 
                 90.5 
                 142 
                 85.3 
                 143 
               
               
                 p (t-test) 
                   
                 0.77 
                   
                 0.56 
                   
                 0.84 
               
               
                 Min 
                 73.7 
                 105 
                 73.7 
                 105 
                 108 
                 73.7 
               
               
                 Max 
                 559 
                 651 
                 429 
                 651 
                 429 
                 651 
               
               
                 n (Patient) 
                 30 
                 48 
                 31 
                 47 
                 30 
                 48 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.56 
                 0.47 
                 0.59 
                 0.56 
                 0.48 
                 0.57 
                 0.59 
                 0.45 
               
               
                 SE 
                 0.063 
                 0.066 
                 0.067 
                 0.062 
                 0.065 
                 0.067 
                 0.063 
                 0.063 
                 0.067 
               
               
                 p Value 
                 0.21 
                 0.39 
                 0.69 
                 0.14 
                 0.35 
                 0.76 
                 0.27 
                 0.14 
                 0.48 
               
               
                 nCohort Recovered 
                 44 
                 48 
                 30 
                 40 
                 46 
                 31 
                 38 
                 42 
                 30 
               
               
                 nCohort Non-recovered 
                 40 
                 33 
                 48 
                 44 
                 35 
                 47 
                 46 
                 39 
                 48 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 172 
                 169 
                 171 
                 172 
                 169 
                 171 
                 172 
               
               
                 Sensitivity 
                 80% 
                 82% 
                 73% 
                 82% 
                 83% 
                 72% 
                 80% 
                 85% 
                 71% 
               
               
                 Specificity 
                 30% 
                 31% 
                 23% 
                 32% 
                 33% 
                 23% 
                 32% 
                 36% 
                 20% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 52% 
                 52% 
                 46% 
                 52% 
                 51% 
                 45% 
                 52% 
                 54% 
                 44% 
               
               
                 Specificity 
                 52% 
                 52% 
                 43% 
                 52% 
                 52% 
                 42% 
                 53% 
                 55% 
                 40% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 334 
                 332 
                 331 
                 334 
                 332 
                 331 
                 334 
               
               
                 Sensitivity 
                 28% 
                 24% 
                 27% 
                 30% 
                 26% 
                 28% 
                 28% 
                 28% 
                 27% 
               
               
                 Specificity 
                 77% 
                 75% 
                 77% 
                 80% 
                 76% 
                 77% 
                 79% 
                 79% 
                 77% 
               
               
                 OR Quartile 2 
                 1.68 
                 2.05 
                 0.819 
                 2.17 
                 2.34 
                 0.763 
                 1.90 
                 3.06 
                 0.607 
               
               
                 p Value 
                 0.32 
                 0.19 
                 0.71 
                 0.13 
                 0.12 
                 0.62 
                 0.21 
                 0.042 
                 0.37 
               
               
                 Lower limit of 95% CI 
                 0.611 
                 0.698 
                 0.284 
                 0.787 
                 0.799 
                 0.265 
                 0.699 
                 1.04 
                 0.204 
               
               
                 Upper limit of 95% CI 
                 4.60 
                 5.99 
                 2.36 
                 5.96 
                 6.84 
                 2.20 
                 5.15 
                 8.95 
                 1.81 
               
               
                 OR Quartile 3 
                 1.21 
                 1.15 
                 0.647 
                 1.21 
                 1.16 
                 0.583 
                 1.21 
                 1.41 
                 0.519 
               
               
                 p Value 
                 0.66 
                 0.75 
                 0.35 
                 0.66 
                 0.75 
                 0.25 
                 0.66 
                 0.44 
                 0.16 
               
               
                 Lower limit of 95% CI 
                 0.514 
                 0.476 
                 0.258 
                 0.514 
                 0.479 
                 0.233 
                 0.513 
                 0.589 
                 0.205 
               
               
                 Upper limit of 95% CI 
                 2.85 
                 2.80 
                 1.62 
                 2.85 
                 2.78 
                 1.46 
                 2.87 
                 3.39 
                 1.31 
               
               
                 OR Quartile 4 
                 1.29 
                 0.960 
                 1.22 
                 1.68 
                 1.10 
                 1.31 
                 1.48 
                 1.44 
                 1.22 
               
               
                 p Value 
                 0.61 
                 0.94 
                 0.71 
                 0.32 
                 0.85 
                 0.62 
                 0.45 
                 0.48 
                 0.71 
               
               
                 Lower limit of 95% CI 
                 0.480 
                 0.343 
                 0.423 
                 0.611 
                 0.398 
                 0.456 
                 0.538 
                 0.522 
                 0.423 
               
               
                 Upper limit of 95% CI 
                 3.47 
                 2.69 
                 3.52 
                 4.60 
                 3.04 
                 3.77 
                 4.06 
                 3.97 
                 3.52 
               
               
                   
               
            
           
         
       
     
     Example 7. Use of C-C Motif Chemokine 14 for Evaluating Renal Status in Patients Admitted to the ICU: Recovery to RIFLE 0 and R from RIFLE I and F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 14 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output during a period starting at 12, 24, 48, or 72 hours after sample collection or at any time within 7 days after sample collection. Two cohorts are defined to represent a “recovered” and a “non-recovered” population. “Recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0) or risk of injury (R). “Non-recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is injury (I) or failure (F). If a patient dies or is placed on renal replacement therapy (RRT) within 9 days of enrollment, the patient is considered “non-recovered”. 
     The ability to distinguish the “recovered” and “non-recovered” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 7.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.474 
                 1.33 
                 0.506 
                 1.33 
                 0.537 
                 1.26 
               
               
                 Average 
                 1.07 
                 2.22 
                 1.11 
                 2.19 
                 1.15 
                 2.17 
               
               
                 Stdev 
                 1.70 
                 2.09 
                 1.74 
                 2.09 
                 1.78 
                 2.08 
               
               
                 p (t-test) 
                   
                 0.023 
                   
                 0.038 
                   
                 0.060 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 19 
                 62 
                 18 
                 63 
                 17 
                 64 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.640 
                 2.07 
                 0.640 
                 1.78 
                 0.640 
                 1.78 
               
               
                 Average 
                 1.44 
                 2.67 
                 1.48 
                 2.55 
                 1.48 
                 2.55 
               
               
                 Stdev 
                 1.75 
                 2.25 
                 1.77 
                 2.24 
                 1.77 
                 2.24 
               
               
                 p (t-test) 
                   
                 0.011 
                   
                 0.024 
                   
                 0.024 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 47 
                 34 
                 45 
                 36 
                 45 
                 36 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.589 
                 1.33 
                 0.537 
                 1.33 
                 0.589 
                 1.33 
               
               
                 Average 
                 1.53 
                 2.23 
                 1.48 
                 2.26 
                 1.52 
                 2.19 
               
               
                 Stdev 
                 1.89 
                 2.09 
                 1.86 
                 2.10 
                 1.90 
                 2.09 
               
               
                 p (t-test) 
                   
                 0.19 
                   
                 0.14 
                   
                 0.21 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 20 
                 52 
                 21 
                 51 
                 20 
                 53 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or  
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.72 
                 0.69 
                 0.64 
                 0.71 
                 0.66 
                 0.65 
                 0.70 
                 0.66 
                 0.64 
               
               
                 SE 
                 0.061 
                 0.061 
                 0.070 
                 0.063 
                 0.061 
                 0.068 
                 0.065 
                 0.061 
                 0.070 
               
               
                 p Value 
                 2.4E−4 
                 0.0022 
                 0.047 
                 0.0010 
                 0.0080 
                 0.026 
                 0.0023 
                 0.0080 
                 0.051 
               
               
                 nCohort Recovered 
                 19 
                 47 
                 20 
                 18 
                 45 
                 21 
                 17 
                 45 
                 20 
               
               
                 nCohort Non-recovered 
                 62 
                 34 
                 52 
                 63 
                 36 
                 51 
                 64 
                 36 
                 53 
               
               
                 Cutoff Quartile 2 
                 0.460 
                 0.460 
                 0.525 
                 0.460 
                 0.460 
                 0.502 
                 0.460 
                 0.460 
                 0.474 
               
               
                 Sensitivity 
                 81% 
                 82% 
                 83% 
                 79% 
                 81% 
                 82% 
                 80% 
                 81% 
                 79% 
               
               
                 Specificity 
                 47% 
                 32% 
                 45% 
                 44% 
                 31% 
                 43% 
                 47% 
                 31% 
                 40% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
               
               
                 Sensitivity 
                 56% 
                 62% 
                 56% 
                 56% 
                 58% 
                 57% 
                 55% 
                 58% 
                 55% 
               
               
                 Specificity 
                 74% 
                 60% 
                 65% 
                 72% 
                 58% 
                 67% 
                 71% 
                 58% 
                 65% 
               
               
                 Cutoff Quartile 4 
                 2.87 
                 2.87 
                 2.94 
                 2.87 
                 2.87 
                 2.94 
                 2.87 
                 2.87 
                 2.91 
               
               
                 Sensitivity 
                 31% 
                 38% 
                 29% 
                 30% 
                 36% 
                 29% 
                 30% 
                 36% 
                 28% 
               
               
                 Specificity 
                 95% 
                 85% 
                 85% 
                 94% 
                 84% 
                 86% 
                 94% 
                 84% 
                 85% 
               
               
                 OR Quartile 2 
                 3.75 
                 2.19 
                 3.91 
                 3.08 
                 1.87 
                 3.50 
                 3.49 
                 1.87 
                 2.55 
               
               
                 p Value 
                 0.018 
                 0.15 
                 0.019 
                 0.048 
                 0.24 
                 0.029 
                 0.030 
                 0.24 
                 0.10 
               
               
                 Lower limit of 95% CI 
                 1.25 
                 0.747 
                 1.25 
                 1.01 
                 0.662 
                 1.14 
                 1.13 
                 0.662 
                 0.836 
               
               
                 Upper limit of 95% CI 
                 11.3 
                 6.40 
                 12.2 
                 9.36 
                 5.29 
                 10.8 
                 10.8 
                 5.29 
                 7.75 
               
               
                 OR Quartile 3 
                 3.63 
                 2.38 
                 2.34 
                 3.25 
                 1.92 
                 2.64 
                 2.90 
                 1.92 
                 2.24 
               
               
                 p Value 
                 0.026 
                 0.060 
                 0.12 
                 0.044 
                 0.15 
                 0.074 
                 0.071 
                 0.15 
                 0.14 
               
               
                 Lower limit of 95% CI 
                 1.16 
                 0.964 
                 0.804 
                 1.03 
                 0.788 
                 0.911 
                 0.914 
                 0.788 
                 0.773 
               
               
                 Upper limit of 95% CI 
                 11.3 
                 5.88 
                 6.82 
                 10.2 
                 4.66 
                 7.63 
                 9.18 
                 4.66 
                 6.52 
               
               
                 OR Quartile 4 
                 7.95 
                 3.54 
                 2.30 
                 7.34 
                 3.07 
                 2.50 
                 6.76 
                 3.07 
                 2.24 
               
               
                 p Value 
                 0.051 
                 0.019 
                 0.23 
                 0.061 
                 0.037 
                 0.19 
                 0.073 
                 0.037 
                 0.25 
               
               
                 Lower limit of 95% CI 
                 0.989 
                 1.23 
                 0.586 
                 0.910 
                 1.07 
                 0.640 
                 0.835 
                 1.07 
                 0.571 
               
               
                 Upper limit of 95% CI 
                 64.0 
                 10.2 
                 9.01 
                 59.2 
                 8.81 
                 9.77 
                 54.6 
                 8.81 
                 8.76 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.541 
                 1.33 
                 0.545 
                 1.33 
                 0.551 
                 1.26 
               
               
                 Average 
                 1.12 
                 2.33 
                 1.16 
                 2.30 
                 1.19 
                 2.27 
               
               
                 Stdev 
                 1.57 
                 2.15 
                 1.60 
                 2.15 
                 1.62 
                 2.14 
               
               
                 p (t-test) 
                   
                 0.0076 
                   
                 0.013 
                   
                 0.021 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 24 
                 56 
                 23 
                 57 
                 22 
                 58 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.640 
                 1.99 
                 0.653 
                 1.78 
                 0.640 
                 1.99 
               
               
                 Average 
                 1.47 
                 2.61 
                 1.50 
                 2.55 
                 1.46 
                 2.56 
               
               
                 Stdev 
                 1.78 
                 2.24 
                 1.79 
                 2.24 
                 1.79 
                 2.21 
               
               
                 p (t-test) 
                   
                 0.018 
                   
                 0.027 
                   
                 0.019 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 45 
                 35 
                 44 
                 36 
                 43 
                 37 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.598 
                 1.33 
                 0.556 
                 1.33 
                 0.598 
                 1.33 
               
               
                 Average 
                 1.20 
                 2.36 
                 1.16 
                 2.40 
                 1.19 
                 2.32 
               
               
                 Stdev 
                 1.17 
                 2.16 
                 1.16 
                 2.17 
                 1.18 
                 2.16 
               
               
                 p (t-test) 
                   
                 0.0063 
                   
                 0.0037 
                   
                 0.0078 
               
               
                 Min 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
               
               
                 Max 
                 4.74 
                 6.66 
                 4.74 
                 6.66 
                 4.74 
                 6.66 
               
               
                 n (Patient) 
                 22 
                 46 
                 23 
                 45 
                 22 
                 47 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.70 
                 0.68 
                 0.67 
                 0.69 
                 0.66 
                 0.68 
                 0.68 
                 0.67 
                 0.66 
               
               
                 SE 
                 0.060 
                 0.061 
                 0.067 
                 0.062 
                 0.062 
                 0.066 
                 0.063 
                 0.061 
                 0.067 
               
               
                 p Value 
                 6.9E−4 
                 0.0036 
                 0.013 
                 0.0023 
                 0.0095 
                 0.0065 
                 0.0047 
                 0.0043 
                 0.017 
               
               
                 nCohort Recovered 
                 24 
                 45 
                 22 
                 23 
                 44 
                 23 
                 22 
                 43 
                 22 
               
               
                 nCohort Non-recovered 
                 56 
                 35 
                 46 
                 57 
                 36 
                 45 
                 58 
                 37 
                 47 
               
               
                 Cutoff Quartile 2 
                 0.457 
                 0.457 
                 0.525 
                 0.457 
                 0.457 
                 0.502 
                 0.457 
                 0.457 
                 0.474 
               
               
                 Sensitivity 
                 82% 
                 86% 
                 83% 
                 81% 
                 83% 
                 82% 
                 81% 
                 84% 
                 79% 
               
               
                 Specificity 
                 42% 
                 33% 
                 41% 
                 39% 
                 32% 
                 39% 
                 41% 
                 33% 
                 36% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
                 1.04 
                 1.04 
                 1.15 
               
               
                 Sensitivity 
                 57% 
                 60% 
                 57% 
                 56% 
                 58% 
                 58% 
                 55% 
                 59% 
                 55% 
               
               
                 Specificity 
                 67% 
                 58% 
                 64% 
                 65% 
                 57% 
                 65% 
                 64% 
                 58% 
                 64% 
               
               
                 Cutoff Quartile 4 
                 2.88 
                 2.88 
                 2.94 
                 2.88 
                 2.88 
                 2.94 
                 2.88 
                 2.88 
                 2.91 
               
               
                 Sensitivity 
                 34% 
                 37% 
                 33% 
                 33% 
                 36% 
                 33% 
                 33% 
                 38% 
                 32% 
               
               
                 Specificity 
                 96% 
                 84% 
                 91% 
                 96% 
                 84% 
                 91% 
                 95% 
                 86% 
                 91% 
               
               
                 OR Quartile 2 
                 3.29 
                 3.00 
                 3.29 
                 2.69 
                 2.33 
                 2.97 
                 2.96 
                 2.49 
                 2.11 
               
               
                 p Value 
                 0.028 
                 0.057 
                 0.041 
                 0.069 
                 0.12 
                 0.060 
                 0.048 
                 0.098 
                 0.19 
               
               
                 Lower limit of 95% CI 
                 1.14 
                 0.968 
                 1.05 
                 0.927 
                 0.791 
                 0.957 
                 1.01 
                 0.845 
                 0.694 
               
               
                 Upper limit of 95% CI 
                 9.50 
                 9.30 
                 10.3 
                 7.80 
                 6.88 
                 9.24 
                 8.66 
                 7.36 
                 6.45 
               
               
                 OR Quartile 3 
                 2.67 
                 2.05 
                 2.28 
                 2.40 
                 1.84 
                 2.57 
                 2.15 
                 2.04 
                 2.17 
               
               
                 p Value 
                 0.055 
                 0.12 
                 0.12 
                 0.088 
                 0.18 
                 0.076 
                 0.14 
                 0.12 
                 0.15 
               
               
                 Lower limit of 95% CI 
                 0.981 
                 0.836 
                 0.799 
                 0.879 
                 0.755 
                 0.905 
                 0.784 
                 0.834 
                 0.764 
               
               
                 Upper limit of 95% CI 
                 7.25 
                 5.04 
                 6.48 
                 6.56 
                 4.49 
                 7.28 
                 5.92 
                 4.98 
                 6.14 
               
               
                 OR Quartile 4 
                 11.8 
                 3.21 
                 4.84 
                 11.0 
                 2.99 
                 5.25 
                 10.2 
                 3.75 
                 4.69 
               
               
                 p Value 
                 0.020 
                 0.031 
                 0.050 
                 0.024 
                 0.042 
                 0.039 
                 0.028 
                 0.017 
                 0.055 
               
               
                 Lower limit of 95% CI 
                 1.48 
                 1.11 
                 0.998 
                 1.38 
                 1.04 
                 1.08 
                 1.28 
                 1.26 
                 0.968 
               
               
                 Upper limit of 95% CI 
                 94.3 
                 9.24 
                 23.5 
                 87.9 
                 8.59 
                 25.4 
                 81.9 
                 11.2 
                 22.7 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and ″non-recovered″ cohorts where recovery starts at 
               
               
                 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.653 
                 1.29 
                 0.838 
                 1.19 
                 1.04 
                 1.19 
               
               
                 Average 
                 1.34 
                 2.54 
                 1.42 
                 2.38 
                 1.45 
                 2.33 
               
               
                 Stdev 
                 1.52 
                 2.33 
                 1.58 
                 2.29 
                 1.59 
                 2.28 
               
               
                 p (t-test) 
                   
                 0.0085 
                   
                 0.032 
                   
                 0.048 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                   
                   
                   
               
               
                 n (Patient) 
                 38 
                 42 
                 34 
                 46 
                 33 
                 47 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.03 
                 1.19 
                 0.848 
                 1.20 
                 0.848 
                 1.20 
               
               
                 Average 
                 1.60 
                 2.41 
                 1.57 
                 2.43 
                 1.57 
                 2.43 
               
               
                 Stdev 
                 1.80 
                 2.27 
                 1.81 
                 2.24 
                 1.81 
                 2.24 
               
               
                 p (t-test) 
                   
                 0.10 
                   
                 0.077 
                   
                 0.077 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 47 
                 32 
                 46 
                 33 
                 46 
                 33 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.04 
                 2.07 
                 1.05 
                 1.33 
                 1.10 
                 1.26 
               
               
                 Average 
                 1.44 
                 2.74 
                 1.56 
                 2.44 
                 1.61 
                 2.38 
               
               
                 Stdev 
                 1.46 
                 2.31 
                 1.54 
                 2.27 
                 1.55 
                 2.26 
               
               
                 p (t-test) 
                   
                 0.015 
                   
                 0.085 
                   
                 0.13 
               
               
                 Min 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
               
               
                 Max 
                 6.26 
                 6.66 
                 6.26 
                 6.66 
                 6.26 
                 6.66 
               
               
                 n (Patient) 
                 29 
                 30 
                 25 
                 35 
                 24 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.64 
                 0.62 
                 0.65 
                 0.61 
                 0.63 
                 0.60 
                 0.60 
                 0.63 
                 0.57 
               
               
                 SE 
                 0.062 
                 0.065 
                 0.071 
                 0.063 
                 0.064 
                 0.074 
                 0.064 
                 0.064 
                 0.075 
               
               
                 p Value 
                 0.021 
                 0.075 
                 0.031 
                 0.072 
                 0.043 
                 0.20 
                 0.13 
                 0.043 
                 0.33 
               
               
                 nCohort Recovered 
                 38 
                 47 
                 29 
                 34 
                 46 
                 25 
                 33 
                 46 
                 24 
               
               
                 nCohort Non-recovered 
                 42 
                 32 
                 30 
                 46 
                 33 
                 35 
                 47 
                 33 
                 36 
               
               
                 Cutoff Quartile 2 
                 0.457 
                 0.454 
                 0.520 
                 0.457 
                 0.454 
                 0.502 
                 0.457 
                 0.454 
                 0.502 
               
               
                 Sensitivity 
                 79% 
                 81% 
                 80% 
                 78% 
                 82% 
                 74% 
                 77% 
                 82% 
                 72% 
               
               
                 Specificity 
                 29% 
                 30% 
                 31% 
                 29% 
                 30% 
                 24% 
                 27% 
                 30% 
                 21% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.20 
                 1.04 
                 1.04 
                 1.19 
                 1.04 
                 1.04 
                 1.19 
               
               
                 Sensitivity 
                 55% 
                 53% 
                 57% 
                 52% 
                 55% 
                 54% 
                 51% 
                 55% 
                 53% 
               
               
                 Specificity 
                 55% 
                 53% 
                 59% 
                 53% 
                 54% 
                 56% 
                 52% 
                 54% 
                 54% 
               
               
                 Cutoff Quartile 4 
                 2.88 
                 2.82 
                 2.98 
                 2.88 
                 2.82 
                 2.94 
                 2.88 
                 2.82 
                 2.94 
               
               
                 Sensitivity 
                 36% 
                 34% 
                 37% 
                 33% 
                 36% 
                 31% 
                 32% 
                 36% 
                 31% 
               
               
                 Specificity 
                 87% 
                 81% 
                 86% 
                 85% 
                 83% 
                 84% 
                 85% 
                 83% 
                 83% 
               
               
                 OR Quartile 2 
                 1.49 
                 1.84 
                 1.80 
                 1.50 
                 1.97 
                 0.912 
                 1.23 
                 1.97 
                 0.684 
               
               
                 p Value 
                 0.44 
                 0.27 
                 0.33 
                 0.43 
                 0.22 
                 0.88 
                 0.69 
                 0.22 
                 0.54 
               
               
                 Lower limit of 95% CI 
                 0.540 
                 0.621 
                 0.547 
                 0.542 
                 0.665 
                 0.277 
                 0.442 
                 0.665 
                 0.201 
               
               
                 Upper limit of 95% CI 
                 4.13 
                 5.44 
                 5.92 
                 4.15 
                 5.83 
                 3.00 
                 3.41 
                 5.83 
                 2.33 
               
               
                 OR Quartile 3 
                 1.50 
                 1.29 
                 1.85 
                 1.23 
                 1.43 
                 1.51 
                 1.11 
                 1.43 
                 1.32 
               
               
                 p Value 
                 0.37 
                 0.58 
                 0.24 
                 0.65 
                 0.44 
                 0.43 
                 0.82 
                 0.44 
                 0.60 
               
               
                 Lower limit of 95% CI 
                 0.619 
                 0.524 
                 0.659 
                 0.505 
                 0.582 
                 0.538 
                 0.455 
                 0.582 
                 0.469 
               
               
                 Upper limit of 95% CI 
                 3.61 
                 3.17 
                 5.21 
                 2.98 
                 3.51 
                 4.24 
                 2.70 
                 3.51 
                 3.72 
               
               
                 OR Quartile 4 
                 3.67 
                 2.21 
                 3.62 
                 2.81 
                 2.71 
                 2.41 
                 2.62 
                 2.71 
                 2.20 
               
               
                 p Value 
                 0.025 
                 0.13 
                 0.051 
                 0.074 
                 0.060 
                 0.18 
                 0.095 
                 0.060 
                 0.23 
               
               
                 Lower limit of 95% CI 
                 1.18 
                 0.790 
                 0.996 
                 0.905 
                 0.958 
                 0.665 
                 0.846 
                 0.958 
                 0.608 
               
               
                 Upper limit of 95% CI 
                 11.4 
                 6.19 
                 13.2 
                 8.70 
                 7.69 
                 8.70 
                 8.14 
                 7.69 
                 7.97 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.629 
                 1.33 
                 0.637 
                 1.26 
                 0.637 
                 1.26 
               
               
                 Average 
                 1.31 
                 2.55 
                 1.33 
                 2.50 
                 1.33 
                 2.50 
               
               
                 Stdev 
                 1.52 
                 2.33 
                 1.53 
                 2.33 
                 1.53 
                 2.33 
               
               
                 p (t-test) 
                   
                 0.0069 
                   
                 0.011 
                   
                 0.011 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 38 
                 41 
                 37 
                 42 
                 37 
                 42 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.653 
                 1.20 
                 0.653 
                 1.20 
                 0.653 
                 1.20 
               
               
                 Average 
                 1.51 
                 2.46 
                 1.51 
                 2.46 
                 1.51 
                 2.46 
               
               
                 Stdev 
                 1.80 
                 2.28 
                 1.80 
                 2.28 
                 1.80 
                 2.28 
               
               
                 p (t-test) 
                   
                 0.062 
                   
                 0.062 
                   
                 0.062 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 46 
                 31 
                 46 
                 31 
                 46 
                 31 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.838 
                 1.68 
                 1.04 
                 1.38 
                 1.04 
                 1.38 
               
               
                 Average 
                 1.57 
                 2.64 
                 1.63 
                 2.57 
                 1.63 
                 2.57 
               
               
                 Stdev 
                 1.69 
                 2.27 
                 1.71 
                 2.27 
                 1.71 
                 2.27 
               
               
                 p (t-test) 
                   
                 0.064 
                   
                 0.11 
                   
                 0.11 
               
               
                 Min 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
                 0.212 
                 0.121 
               
               
                 Max 
                 6.26 
                 6.66 
                 6.26 
                 6.66 
                 6.26 
                 6.66 
               
               
                 n (Patient) 
                 20 
                 32 
                 19 
                 33 
                 19 
                 33 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or  
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.67 
                 0.64 
                 0.66 
                 0.65 
                 0.64 
                 0.63 
                 0.65 
                 0.64 
                 0.63 
               
               
                 SE 
                 0.060 
                 0.065 
                 0.076 
                 0.061 
                 0.065 
                 0.078 
                 0.061 
                 0.065 
                 0.078 
               
               
                 p Value 
                 0.0045 
                 0.034 
                 0.036 
                 0.012 
                 0.034 
                 0.089 
                 0.012 
                 0.034 
                 0.089 
               
               
                 nCohort Recovered 
                 38 
                 46 
                 20 
                 37 
                 46 
                 19 
                 37 
                 46 
                 19 
               
               
                 nCohort Non-recovered 
                 41 
                 31 
                 32 
                 42 
                 31 
                 33 
                 42 
                 31 
                 33 
               
               
                 Cutoff Quartile 2 
                 0.454 
                 0.448 
                 0.525 
                 0.454 
                 0.448 
                 0.525 
                 0.454 
                 0.448 
                 0.525 
               
               
                 Sensitivity 
                 83% 
                 81% 
                 81% 
                 81% 
                 81% 
                 79% 
                 81% 
                 81% 
                 79% 
               
               
                 Specificity 
                 34% 
                 30% 
                 35% 
                 32% 
                 30% 
                 32% 
                 32% 
                 30% 
                 32% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.03 
                 1.19 
                 1.04 
                 1.03 
                 1.19 
                 1.04 
                 1.03 
                 1.19 
               
               
                 Sensitivity 
                 56% 
                 55% 
                 59% 
                 55% 
                 55% 
                 58% 
                 55% 
                 55% 
                 58% 
               
               
                 Specificity 
                 58% 
                 54% 
                 65% 
                 57% 
                 54% 
                 63% 
                 57% 
                 54% 
                 63% 
               
               
                 Cutoff Quartile 4 
                 2.82 
                 2.75 
                 3.17 
                 2.82 
                 2.75 
                 3.17 
                 2.82 
                 2.75 
                 3.17 
               
               
                 Sensitivity 
                 37% 
                 39% 
                 28% 
                 36% 
                 39% 
                 27% 
                 36% 
                 39% 
                 27% 
               
               
                 Specificity 
                 87% 
                 85% 
                 80% 
                 86% 
                 85% 
                 79% 
                 86% 
                 85% 
                 79% 
               
               
                 OR Quartile 2 
                 2.53 
                 1.82 
                 2.33 
                 2.04 
                 1.82 
                 1.71 
                 2.04 
                 1.82 
                 1.71 
               
               
                 p Value 
                 0.085 
                 0.28 
                 0.19 
                 0.18 
                 0.28 
                 0.41 
                 0.18 
                 0.28 
                 0.41 
               
               
                 Lower limit of 95% CI 
                 0.880 
                 0.613 
                 0.650 
                 0.726 
                 0.613 
                 0.478 
                 0.726 
                 0.613 
                 0.478 
               
               
                 Upper limit of 95% CI 
                 7.25 
                 5.42 
                 8.37 
                 5.73 
                 5.42 
                 6.15 
                 5.73 
                 5.42 
                 6.15 
               
               
                 OR Quartile 3 
                 1.76 
                 1.45 
                 2.71 
                 1.59 
                 1.45 
                 2.33 
                 1.59 
                 1.45 
                 2.33 
               
               
                 p Value 
                 0.22 
                 0.43 
                 0.091 
                 0.31 
                 0.43 
                 0.15 
                 0.31 
                 0.43 
                 0.15 
               
               
                 Lower limit of 95% CI 
                 0.720 
                 0.579 
                 0.852 
                 0.652 
                 0.579 
                 0.729 
                 0.652 
                 0.579 
                 0.729 
               
               
                 Upper limit of 95% CI 
                 4.29 
                 3.61 
                 8.64 
                 3.87 
                 3.61 
                 7.42 
                 3.87 
                 3.61 
                 7.42 
               
               
                 OR Quartile 4 
                 3.81 
                 3.52 
                 1.57 
                 3.56 
                 3.52 
                 1.41 
                 3.56 
                 3.52 
                 1.41 
               
               
                 p Value 
                 0.021 
                 0.023 
                 0.51 
                 0.028 
                 0.023 
                 0.62 
                 0.028 
                 0.023 
                 0.62 
               
               
                 Lower limit of 95% CI 
                 1.22 
                 1.19 
                 0.410 
                 1.14 
                 1.19 
                 0.367 
                 1.14 
                 1.19 
                 0.367 
               
               
                 Upper limit of 95% CI 
                 11.8 
                 10.4 
                 5.97 
                 11.1 
                 10.4 
                 5.39 
                 11.1 
                 10.4 
                 5.39 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 within 7 days after sample collection and renal status is assessed by serum creatinine 
               
               
                 (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.665 
                 1.68 
                 0.639 
                 1.38 
                 0.639 
                 1.38 
               
               
                 Average 
                 1.54 
                 2.54 
                 1.47 
                 2.55 
                 1.47 
                 2.55 
               
               
                 Stdev 
                 1.85 
                 2.19 
                 1.76 
                 2.24 
                 1.76 
                 2.24 
               
               
                 p (t-test) 
                   
                 0.038 
                   
                 0.022 
                   
                 0.022 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 51 
                 32 
                 48 
                 35 
                 48 
                 35 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.911 
                 1.20 
                 0.911 
                 1.20 
                 0.911 
                 1.20 
               
               
                 Average 
                 1.74 
                 2.48 
                 1.72 
                 2.47 
                 1.72 
                 2.47 
               
               
                 Stdev 
                 1.89 
                 2.36 
                 1.90 
                 2.31 
                 1.90 
                 2.31 
               
               
                 p (t-test) 
                   
                 0.20 
                   
                 0.17 
                   
                 0.17 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
                 0.121 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 58 
                 23 
                 56 
                 25 
                 56 
                 25 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.727 
                 1.19 
                 0.665 
                 1.29 
                 0.653 
                 1.20 
               
               
                 Average 
                 1.69 
                 2.23 
                 1.43 
                 2.43 
                 1.44 
                 2.38 
               
               
                 Stdev 
                 2.09 
                 2.11 
                 1.68 
                 2.20 
                 1.70 
                 2.19 
               
               
                 p (t-test) 
                   
                 0.27 
                   
                 0.029 
                   
                 0.039 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
                 0.208 
                 0.121 
               
               
                 Max 
                 8.44 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 40 
                 39 
                 41 
                 38 
                 40 
                 39 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.66 
                 0.59 
                 0.59 
                 0.67 
                 0.60 
                 0.64 
                 0.67 
                 0.60 
                 0.64 
               
               
                 SE 
                 0.063 
                 0.072 
                 0.064 
                 0.061 
                 0.070 
                 0.063 
                 0.061 
                 0.070 
                 0.062 
               
               
                 p Value 
                 0.014 
                 0.22 
                 0.16 
                 0.0064 
                 0.15 
                 0.026 
                 0.0064 
                 0.15 
                 0.026 
               
               
                 nCohort  
                 51 
                 58 
                 40 
                 48 
                 56 
                 41 
                 48 
                 56 
                 40 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 32 
                 23 
                 39 
                 35 
                 25 
                 38 
                 35 
                 25 
                 39 
               
               
                 Non-recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.467 
                 0.460 
                 0.493 
                 0.467 
                 0.460 
                 0.493 
                 0.467 
                 0.460 
                 0.493 
               
               
                 Sensitivity 
                 81% 
                 74% 
                 79% 
                 83% 
                 76% 
                 82% 
                 83% 
                 76% 
                 82% 
               
               
                 Specificity 
                 29% 
                 26% 
                 30% 
                 31% 
                 27% 
                 32% 
                 31% 
                 27% 
                 32% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
                 1.04 
               
               
                 Sensitivity 
                 62% 
                 57% 
                 54% 
                 60% 
                 56% 
                 58% 
                 60% 
                 56% 
                 56% 
               
               
                 Specificity 
                 59% 
                 53% 
                 55% 
                 58% 
                 54% 
                 59% 
                 58% 
                 54% 
                 57% 
               
               
                 Cutoff Quartile 4 
                 2.82 
                 2.87 
                 2.82 
                 2.82 
                 2.87 
                 2.82 
                 2.82 
                 2.87 
                 2.82 
               
               
                 Sensitivity 
                 38% 
                 30% 
                 31% 
                 37% 
                 32% 
                 34% 
                 37% 
                 32% 
                 33% 
               
               
                 Specificity 
                 82% 
                 78% 
                 80% 
                 83% 
                 79% 
                 83% 
                 83% 
                 79% 
                 82% 
               
               
                 OR Quartile 2 
                 1.81 
                 0.988 
                 1.66 
                 2.20 
                 1.16 
                 2.06 
                 2.20 
                 1.16 
                 2.20 
               
               
                 p Value 
                 0.28 
                 0.98 
                 0.33 
                 0.15 
                 0.79 
                 0.18 
                 0.15 
                 0.79 
                 0.14 
               
               
                 Lower limit of  
                 0.618 
                 0.329 
                 0.593 
                 0.753 
                 0.389 
                 0.719 
                 0.753 
                 0.389 
                 0.769 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 5.28 
                 2.97 
                 4.65 
                 6.41 
                 3.45 
                 5.88 
                 6.41 
                 3.45 
                 6.30 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 2.38 
                 1.49 
                 1.43 
                 2.10 
                 1.47 
                 1.94 
                 2.10 
                 1.47 
                 1.75 
               
               
                 p Value 
                 0.061 
                 0.42 
                 0.43 
                 0.10 
                 0.43 
                 0.15 
                 0.10 
                 0.43 
                 0.22 
               
               
                 Lower limit of  
                 0.961 
                 0.564 
                 0.588 
                 0.865 
                 0.569 
                 0.793 
                 0.865 
                 0.569 
                 0.718 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 5.90 
                 3.95 
                 3.46 
                 5.10 
                 3.79 
                 4.75 
                 5.10 
                 3.79 
                 4.27 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 2.80 
                 1.51 
                 1.78 
                 2.95 
                 1.73 
                 2.53 
                 2.95 
                 1.73 
                 2.36 
               
               
                 p Value 
                 0.047 
                 0.45 
                 0.27 
                 0.038 
                 0.31 
                 0.085 
                 0.038 
                 0.31 
                 0.11 
               
               
                 Lower limit of  
                 1.01 
                 0.513 
                 0.634 
                 1.06 
                 0.601 
                 0.880 
                 1.06 
                 0.601 
                 0.823 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 7.73 
                 4.47 
                 4.98 
                 8.22 
                 4.96 
                 7.25 
                 8.22 
                 4.96 
                 6.76 
               
               
                 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 207 
                 268 
                 211 
                 260 
                 216 
                 258 
               
               
                 Average 
                 205 
                 284 
                 207 
                 282 
                 207 
                 281 
               
               
                 Stdev 
                 82.7 
                 126 
                 84.7 
                 126 
                 87.0 
                 125 
               
               
                 p (t-test) 
                   
                 0.0028 
                   
                 0.0050 
                   
                 0.0076 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 360 
                 651 
                 360 
                 651 
                 360 
                 651 
               
               
                 n (Patient) 
                 20 
                 62 
                 19 
                 63 
                 18 
                 64 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 239 
                 281 
                 239 
                 276 
                 239 
                 276 
               
               
                 Average 
                 240 
                 297 
                 241 
                 294 
                 241 
                 294 
               
               
                 Stdev 
                 108 
                 133 
                 110 
                 131 
                 110 
                 131 
               
               
                 p (t-test) 
                   
                 0.044 
                   
                 0.057 
                   
                 0.057 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 46 
                 35 
                 44 
                 37 
                 44 
                 37 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 221 
                 258 
                 216 
                 260 
                 249 
                 257 
               
               
                 Average 
                 237 
                 286 
                 234 
                 288 
                 239 
                 284 
               
               
                 Stdev 
                 106 
                 128 
                 104 
                 129 
                 106 
                 128 
               
               
                 p (t-test) 
                   
                 0.10 
                   
                 0.073 
                   
                 0.13 
               
               
                 Min 
                 73.7 
                 110 
                 73.7 
                 110 
                 73.7 
                 110 
               
               
                 Max 
                 421 
                 651 
                 421 
                 651 
                 421 
                 651 
               
               
                 n (Patient) 
                 21 
                 50 
                 22 
                 49 
                 21 
                 51 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.68 
                 0.62 
                 0.60 
                 0.67 
                 0.61 
                 0.62 
                 0.67 
                 0.61 
                 0.59 
               
               
                 SE 
                 0.064 
                 0.063 
                 0.071 
                 0.066 
                 0.063 
                 0.070 
                 0.067 
                 0.063 
                 0.072 
               
               
                 p Value 
                 0.0044 
                 0.055 
                 0.15 
                 0.0080 
                 0.072 
                 0.098 
                 0.011 
                 0.072 
                 0.20 
               
               
                 nCohort Recovered 
                 20 
                 46 
                 21 
                 19 
                 44 
                 22 
                 18 
                 44 
                 21 
               
               
                 nCohort Non-recovered 
                 62 
                 35 
                 50 
                 63 
                 37 
                 49 
                 64 
                 37 
                 51 
               
               
                 Cutoff Quartile 2 
                 172 
                 171 
                 174 
                 172 
                 171 
                 174 
                 172 
                 171 
                 175 
               
               
                 Sensitivity 
                 79% 
                 83% 
                 80% 
                 79% 
                 84% 
                 80% 
                 80% 
                 84% 
                 80% 
               
               
                 Specificity 
                 40% 
                 33% 
                 38% 
                 42% 
                 34% 
                 36% 
                 44% 
                 34% 
                 38% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 253 
                 249 
                 249 
                 253 
                 249 
                 249 
                 251 
               
               
                 Sensitivity 
                 55% 
                 54% 
                 52% 
                 54% 
                 54% 
                 53% 
                 53% 
                 54% 
                 51% 
               
               
                 Specificity 
                 65% 
                 54% 
                 57% 
                 63% 
                 55% 
                 59% 
                 61% 
                 55% 
                 52% 
               
               
                 Cutoff Quartile 4 
                 331 
                 331 
                 339 
                 331 
                 331 
                 339 
                 331 
                 331 
                 337 
               
               
                 Sensitivity 
                 29% 
                 34% 
                 28% 
                 29% 
                 32% 
                 29% 
                 28% 
                 32% 
                 27% 
               
               
                 Specificity 
                 85% 
                 83% 
                 81% 
                 84% 
                 82% 
                 82% 
                 83% 
                 82% 
                 81% 
               
               
                 OR Quartile 2 
                 2.51 
                 2.34 
                 2.46 
                 2.80 
                 2.67 
                 2.23 
                 3.14 
                 2.67 
                 2.52 
               
               
                 p Value 
                 0.096 
                 0.12 
                 0.12 
                 0.066 
                 0.073 
                 0.16 
                 0.044 
                 0.073 
                 0.11 
               
               
                 Lower limit of 95% CI 
                 0.850 
                 0.799 
                 0.803 
                 0.935 
                 0.913 
                 0.733 
                 1.03 
                 0.913 
                 0.824 
               
               
                 Upper limit of 95% CI 
                 7.43 
                 6.84 
                 7.55 
                 8.37 
                 7.82 
                 6.78 
                 9.54 
                 7.82 
                 7.73 
               
               
                 OR Quartile 3 
                 2.26 
                 1.41 
                 1.44 
                 2.01 
                 1.41 
                 1.63 
                 1.78 
                 1.41 
                 1.14 
               
               
                 p Value 
                 0.13 
                 0.44 
                 0.48 
                 0.19 
                 0.44 
                 0.35 
                 0.29 
                 0.44 
                 0.80 
               
               
                 Lower limit of 95% CI 
                 0.792 
                 0.585 
                 0.517 
                 0.699 
                 0.587 
                 0.590 
                 0.613 
                 0.587 
                 0.414 
               
               
                 Upper limit of 95% CI 
                 6.42 
                 3.42 
                 4.03 
                 5.78 
                 3.40 
                 4.52 
                 5.18 
                 3.40 
                 3.16 
               
               
                 OR Quartile 4 
                 2.32 
                 2.48 
                 1.65 
                 2.13 
                 2.16 
                 1.80 
                 1.96 
                 2.16 
                 1.61 
               
               
                 p Value 
                 0.22 
                 0.085 
                 0.43 
                 0.27 
                 0.14 
                 0.36 
                 0.33 
                 0.14 
                 0.46 
               
               
                 Lower limit of 95% CI 
                 0.604 
                 0.882 
                 0.473 
                 0.554 
                 0.771 
                 0.517 
                 0.505 
                 0.771 
                 0.460 
               
               
                 Upper limit of 95% CI 
                 8.89 
                 6.97 
                 5.78 
                 8.22 
                 6.05 
                 6.27 
                 7.58 
                 6.05 
                 5.62 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 216 
                 277 
                 221 
                 260 
                 235 
                 258 
               
               
                 Average 
                 217 
                 294 
                 221 
                 288 
                 221 
                 287 
               
               
                 Stdev 
                 84.9 
                 127 
                 88.3 
                 126 
                 90.2 
                 126 
               
               
                 p (t-test) 
                   
                 0.0023 
                   
                 0.0095 
                   
                 0.014 
               
               
                 Min 
                 73.7 
                 110 
                 73.7 
                 110 
                 73.7 
                 110 
               
               
                 Max 
                 360 
                 651 
                 360 
                 651 
                 360 
                 651 
               
               
                 n (Patient) 
                 26 
                 54 
                 23 
                 57 
                 22 
                 58 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 239 
                 281 
                 243 
                 279 
                 239 
                 281 
               
               
                 Average 
                 245 
                 302 
                 247 
                 299 
                 245 
                 299 
               
               
                 Stdev 
                 115 
                 122 
                 116 
                 122 
                 117 
                 120 
               
               
                 p (t-test) 
                   
                 0.042 
                   
                 0.061 
                   
                 0.053 
               
               
                 Min 
                 73.7 
                 123 
                 73.7 
                 123 
                 73.7 
                 123 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 46 
                 33 
                 45 
                 34 
                 44 
                 35 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 243 
                 258 
                 237 
                 257 
                 253 
                 249 
               
               
                 Average 
                 241 
                 291 
                 242 
                 288 
                 247 
                 284 
               
               
                 Stdev 
                 99.6 
                 133 
                 100 
                 133 
                 101 
                 131 
               
               
                 p (t-test) 
                   
                 0.088 
                   
                 0.12 
                   
                 0.21 
               
               
                 Min 
                 73.7 
                 110 
                 73.7 
                 110 
                 73.7 
                 110 
               
               
                 Max 
                 421 
                 651 
                 421 
                 651 
                 421 
                 651 
               
               
                 n (Patient) 
                 25 
                 44 
                 24 
                 45 
                 23 
                 47 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or  
                   
                   
                 sCr or  
                   
                   
                 sCr or  
                   
                   
               
               
                   
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.67 
                 0.64 
                 0.59 
                 0.65 
                 0.62 
                 0.58 
                 0.64 
                 0.63 
                 0.56 
               
               
                 SE 
                 0.061 
                 0.064 
                 0.070 
                 0.065 
                 0.064 
                 0.071 
                 0.066 
                 0.064 
                 0.072 
               
               
                 p Value 
                 0.0047 
                 0.032 
                 0.19 
                 0.025 
                 0.052 
                 0.25 
                 0.035 
                 0.039 
                 0.43 
               
               
                 nCohort  
                 26 
                 46 
                 25 
                 23 
                 45 
                 24 
                 22 
                 44 
                 23 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Non- 
                 54 
                 33 
                 44 
                 57 
                 34 
                 45 
                 58 
                 35 
                 47 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 176 
                 175 
                 177 
                 176 
                 175 
                 177 
                 176 
                 175 
                 178 
               
               
                 Sensitivity 
                 81% 
                 85% 
                 80% 
                 81% 
                 85% 
                 78% 
                 81% 
                 86% 
                 79% 
               
               
                 Specificity 
                 38% 
                 33% 
                 36% 
                 39% 
                 33% 
                 33% 
                 41% 
                 34% 
                 35% 
               
               
                 Cutoff Quartile 3 
                 251 
                 249 
                 253 
                 251 
                 249 
                 253 
                 251 
                 249 
                 251 
               
               
                 Sensitivity 
                 56% 
                 55% 
                 52% 
                 53% 
                 53% 
                 51% 
                 52% 
                 54% 
                 49% 
               
               
                 Specificity 
                 62% 
                 54% 
                 56% 
                 57% 
                 53% 
                 54% 
                 55% 
                 55% 
                 48% 
               
               
                 Cutoff Quartile 4 
                 332 
                 333 
                 335 
                 332 
                 333 
                 335 
                 332 
                 333 
                 334 
               
               
                 Sensitivity 
                 31% 
                 33% 
                 30% 
                 30% 
                 32% 
                 29% 
                 29% 
                 31% 
                 28% 
               
               
                 Specificity 
                 88% 
                 80% 
                 84% 
                 87% 
                 80% 
                 83% 
                 86% 
                 80% 
                 78% 
               
               
                 OR Quartile 2 
                 2.75 
                 2.71 
                 2.19 
                 2.69 
                 2.90 
                 1.75 
                 2.96 
                 3.10 
                 1.97 
               
               
                 p Value 
                 0.058 
                 0.085 
                 0.16 
                 0.069 
                 0.066 
                 0.32 
                 0.048 
                 0.050 
                 0.23 
               
               
                 Lower limit of  
                 0.965 
                 0.872 
                 0.730 
                 0.927 
                 0.933 
                 0.581 
                 1.01 
                 0.999 
                 0.653 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 7.83 
                 8.42 
                 6.55 
                 7.80 
                 9.01 
                 5.27 
                 8.66 
                 9.64 
                 5.97 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 2.00 
                 1.43 
                 1.39 
                 1.44 
                 1.29 
                 1.24 
                 1.29 
                 1.42 
                 0.878 
               
               
                 p Value 
                 0.15 
                 0.44 
                 0.51 
                 0.46 
                 0.58 
                 0.68 
                 0.62 
                 0.44 
                 0.80 
               
               
                 Lower limit of  
                 0.769 
                 0.582 
                 0.520 
                 0.545 
                 0.527 
                 0.458 
                 0.480 
                 0.584 
                 0.324 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 5.20 
                 3.51 
                 3.74 
                 3.83 
                 3.14 
                 3.34 
                 3.44 
                 3.47 
                 2.38 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 3.52 
                 2.06 
                 2.20 
                 2.83 
                 1.91 
                 2.03 
                 2.63 
                 1.78 
                 1.38 
               
               
                 p Value 
                 0.064 
                 0.17 
                 0.22 
                 0.13 
                 0.21 
                 0.27 
                 0.16 
                 0.27 
                 0.60 
               
               
                 Lower limit of  
                 0.929 
                 0.736 
                 0.631 
                 0.742 
                 0.687 
                 0.581 
                 0.686 
                 0.641 
                 0.423 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 13.4 
                 5.74 
                 7.69 
                 10.8 
                 5.33 
                 7.11 
                 10.1 
                 4.96 
                 4.48 
               
               
                 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 242 
                 257 
                 251 
                 249 
                 253 
                 248 
               
               
                 Average 
                 243 
                 293 
                 244 
                 288 
                 248 
                 285 
               
               
                 Stdev 
                 99.5 
                 136 
                 100 
                 133 
                 100 
                 134 
               
               
                 p (t-test) 
                   
                 0.072 
                   
                 0.11 
                   
                 0.18 
               
               
                 Min 
                 73.7 
                 114 
                 73.7 
                 114 
                 73.7 
                 114 
               
               
                 Max 
                 446 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                 36 
                 41 
                 32 
                 45 
                 31 
                 46 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 246 
                 263 
                 243 
                 276 
                 243 
                 276 
               
               
                 Average 
                 251 
                 297 
                 250 
                 297 
                 250 
                 297 
               
               
                 Stdev 
                 117 
                 127 
                 118 
                 125 
                 118 
                 125 
               
               
                 p (t-test) 
                   
                 0.12 
                   
                 0.11 
                   
                 0.11 
               
               
                 Min 
                 73.7 
                 123 
                 73.7 
                 123 
                 73.7 
                 123 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 46 
                 30 
                 45 
                 31 
                 45 
                 31 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 281 
                 246 
                 288 
                 231 
                 295 
                 227 
               
               
                 Average 
                 266 
                 293 
                 275 
                 283 
                 281 
                 279 
               
               
                 Stdev 
                 90.7 
                 146 
                 87.4 
                 141 
                 85.0 
                 141 
               
               
                 p (t-test) 
                   
                 0.41 
                   
                 0.79 
                   
                 0.96 
               
               
                 Min 
                 73.7 
                 114 
                 73.7 
                 114 
                 73.7 
                 114 
               
               
                 Max 
                 429 
                 651 
                 429 
                 651 
                 429 
                 651 
               
               
                 n (Patient) 
                 27 
                 30 
                 23 
                 35 
                 22 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.59 
                 0.60 
                 0.49 
                 0.57 
                 0.61 
                 0.43 
                 0.55 
                 0.61 
                 0.40 
               
               
                 SE 
                 0.065 
                 0.067 
                 0.077 
                 0.066 
                 0.067 
                 0.077 
                 0.067 
                 0.067 
                 0.076 
               
               
                 p Value 
                 0.18 
                 0.13 
                 0.92 
                 0.29 
                 0.11 
                 0.39 
                 0.44 
                 0.11 
                 0.20 
               
               
                 nCohort Recovered 
                 36 
                 46 
                 27 
                 32 
                 45 
                 23 
                 31 
                 45 
                 22 
               
               
                 nCohort Non-recovered 
                 41 
                 30 
                 30 
                 45 
                 31 
                 35 
                 46 
                 31 
                 36 
               
               
                 Cutoff Quartile 2 
                 174 
                 173 
                 185 
                 174 
                 173 
                 187 
                 174 
                 173 
                 187 
               
               
                 Sensitivity 
                 80% 
                 87% 
                 70% 
                 80% 
                 87% 
                 69% 
                 78% 
                 87% 
                 67% 
               
               
                 Specificity 
                 33% 
                 33% 
                 22% 
                 34% 
                 33% 
                 17% 
                 32% 
                 33% 
                 14% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 257 
                 249 
                 249 
                 255 
                 249 
                 249 
                 255 
               
               
                 Sensitivity 
                 51% 
                 53% 
                 43% 
                 49% 
                 55% 
                 43% 
                 48% 
                 55% 
                 42% 
               
               
                 Specificity 
                 53% 
                 52% 
                 44% 
                 50% 
                 53% 
                 39% 
                 48% 
                 53% 
                 36% 
               
               
                 Cutoff Quartile 4 
                 335 
                 334 
                 335 
                 335 
                 334 
                 334 
                 335 
                 334 
                 334 
               
               
                 Sensitivity 
                 27% 
                 30% 
                 27% 
                 27% 
                 29% 
                 26% 
                 26% 
                 29% 
                 25% 
               
               
                 Specificity 
                 78% 
                 78% 
                 78% 
                 78% 
                 78% 
                 74% 
                 77% 
                 78% 
                 73% 
               
               
                 OR Quartile 2 
                 2.06 
                 3.15 
                 0.667 
                 2.10 
                 3.38 
                 0.459 
                 1.71 
                 3.38 
                 0.316 
               
               
                 p Value 
                 0.17 
                 0.066 
                 0.51 
                 0.16 
                 0.051 
                 0.24 
                 0.30 
                 0.051 
                 0.11 
               
               
                 Lower limit of 95% CI 
                 0.731 
                 0.929 
                 0.201 
                 0.746 
                 0.997 
                 0.126 
                 0.613 
                 0.997 
                 0.0778 
               
               
                 Upper limit of 95% CI 
                 5.82 
                 10.7 
                 2.21 
                 5.88 
                 11.4 
                 1.67 
                 4.79 
                 11.4 
                 1.28 
               
               
                 OR Quartile 3 
                 1.17 
                 1.25 
                 0.612 
                 0.957 
                 1.39 
                 0.482 
                 0.859 
                 1.39 
                 0.408 
               
               
                 p Value 
                 0.73 
                 0.64 
                 0.36 
                 0.92 
                 0.48 
                 0.18 
                 0.74 
                 0.48 
                 0.11 
               
               
                 Lower limit of 95% CI 
                 0.479 
                 0.496 
                 0.215 
                 0.386 
                 0.554 
                 0.165 
                 0.345 
                 0.554 
                 0.137 
               
               
                 Upper limit of 95% CI 
                 2.88 
                 3.13 
                 1.74 
                 2.37 
                 3.48 
                 1.41 
                 2.14 
                 3.48 
                 1.22 
               
               
                 OR Quartile 4 
                 1.28 
                 1.54 
                 1.27 
                 1.30 
                 1.43 
                 0.981 
                 1.21 
                 1.43 
                 0.889 
               
               
                 p Value 
                 0.64 
                 0.42 
                 0.70 
                 0.63 
                 0.50 
                 0.97 
                 0.73 
                 0.50 
                 0.85 
               
               
                 Lower limit of 95% CI 
                 0.451 
                 0.540 
                 0.377 
                 0.447 
                 0.503 
                 0.295 
                 0.416 
                 0.503 
                 0.267 
               
               
                 Upper limit of 95% CI 
                 3.65 
                 4.41 
                 4.29 
                 3.78 
                 4.08 
                 3.26 
                 3.52 
                 4.08 
                 2.96 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 239 
                 267 
                 243 
                 257 
                 243 
                 257 
               
               
                 Average 
                 235 
                 300 
                 237 
                 296 
                 237 
                 296 
               
               
                 Stdev 
                 95.7 
                 135 
                 95.9 
                 135 
                 95.9 
                 135 
               
               
                 p (t-test) 
                   
                 0.020 
                   
                 0.034 
                   
                 0.034 
               
               
                 Min 
                 73.7 
                 123 
                 73.7 
                 123 
                 73.7 
                 123 
               
               
                 Max 
                 421 
                 651 
                 421 
                 651 
                 421 
                 651 
               
               
                 n (Patient) 
                 36 
                 38 
                 35 
                 39 
                 35 
                 39 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 246 
                 249 
                 246 
                 249 
                 246 
                 249 
               
               
                 Average 
                 249 
                 293 
                 249 
                 293 
                 249 
                 293 
               
               
                 Stdev 
                 115 
                 127 
                 115 
                 127 
                 115 
                 127 
               
               
                 p (t-test) 
                   
                 0.15 
                   
                 0.15 
                   
                 0.15 
               
               
                 Min 
                 73.7 
                 123 
                 73.7 
                 123 
                 73.7 
                 123 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 44 
                 29 
                 44 
                 29 
                 44 
                 29 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 273 
                 253 
                 281 
                 249 
                 281 
                 249 
               
               
                 Average 
                 262 
                 302 
                 269 
                 297 
                 269 
                 297 
               
               
                 Stdev 
                 85.6 
                 143 
                 83.3 
                 143 
                 83.3 
                 143 
               
               
                 p (t-test) 
                   
                 0.24 
                   
                 0.39 
                   
                 0.39 
               
               
                 Min 
                 73.7 
                 149 
                 73.7 
                 148 
                 73.7 
                 148 
               
               
                 Max 
                 395 
                 651 
                 395 
                 651 
                 395 
                 651 
               
               
                 n (Patient) 
                 18 
                 30 
                 17 
                 31 
                 17 
                 31 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or  
                   
                   
                 sCr or  
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.63 
                 0.59 
                 0.52 
                 0.61 
                 0.59 
                 0.48 
                 0.61 
                 0.59 
                 0.48 
               
               
                 SE 
                 0.065 
                 0.069 
                 0.087 
                 0.065 
                 0.069 
                 0.088 
                 0.065 
                 0.069 
                 0.088 
               
               
                 p Value 
                 0.048 
                 0.17 
                 0.80 
                 0.096 
                 0.17 
                 0.84 
                 0.096 
                 0.17 
                 0.84 
               
               
                 nCohort Recovered 
                 36 
                 44 
                 18 
                 35 
                 44 
                 17 
                 35 
                 44 
                 17 
               
               
                 nCohort Non-recovered 
                 38 
                 29 
                 30 
                 39 
                 29 
                 31 
                 39 
                 29 
                 31 
               
               
                 Cutoff Quartile 2 
                 175 
                 174 
                 201 
                 175 
                 174 
                 201 
                 175 
                 174 
                 201 
               
               
                 Sensitivity 
                 84% 
                 83% 
                 73% 
                 82% 
                 83% 
                 71% 
                 82% 
                 83% 
                 71% 
               
               
                 Specificity 
                 36% 
                 32% 
                 22% 
                 34% 
                 32% 
                 18% 
                 34% 
                 32% 
                 18% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 261 
                 249 
                 249 
                 261 
                 249 
                 249 
                 261 
               
               
                 Sensitivity 
                 55% 
                 52% 
                 47% 
                 54% 
                 52% 
                 45% 
                 54% 
                 52% 
                 45% 
               
               
                 Specificity 
                 56% 
                 52% 
                 44% 
                 54% 
                 52% 
                 41% 
                 54% 
                 52% 
                 41% 
               
               
                 Cutoff Quartile 4 
                 331 
                 329 
                 345 
                 331 
                 329 
                 345 
                 331 
                 329 
                 345 
               
               
                 Sensitivity 
                 29% 
                 28% 
                 30% 
                 28% 
                 28% 
                 29% 
                 28% 
                 28% 
                 29% 
               
               
                 Specificity 
                 78% 
                 77% 
                 83% 
                 77% 
                 77% 
                 82% 
                 77% 
                 77% 
                 82% 
               
               
                 OR Quartile 2 
                 3.01 
                 2.24 
                 0.786 
                 2.39 
                 2.24 
                 0.524 
                 2.39 
                 2.24 
                 0.524 
               
               
                 p Value 
                 0.050 
                 0.17 
                 0.73 
                 0.11 
                 0.17 
                 0.39 
                 0.11 
                 0.17 
                 0.39 
               
               
                 Lower limit of 95% CI 
                 0.998 
                 0.707 
                 0.199 
                 0.814 
                 0.707 
                 0.121 
                 0.814 
                 0.707 
                 0.121 
               
               
                 Upper limit of 95% CI 
                 9.11 
                 7.10 
                 3.11 
                 6.99 
                 7.10 
                 2.27 
                 6.99 
                 7.10 
                 2.27 
               
               
                 OR Quartile 3 
                 1.54 
                 1.17 
                 0.700 
                 1.39 
                 1.17 
                 0.576 
                 1.39 
                 1.17 
                 0.576 
               
               
                 p Value 
                 0.35 
                 0.74 
                 0.55 
                 0.49 
                 0.74 
                 0.37 
                 0.49 
                 0.74 
                 0.37 
               
               
                 Lower limit of 95% CI 
                 0.617 
                 0.459 
                 0.216 
                 0.554 
                 0.459 
                 0.174 
                 0.554 
                 0.459 
                 0.174 
               
               
                 Upper limit of 95% CI 
                 3.86 
                 3.00 
                 2.26 
                 3.46 
                 3.00 
                 1.91 
                 3.46 
                 3.00 
                 1.91 
               
               
                 OR Quartile 4 
                 1.43 
                 1.30 
                 2.14 
                 1.33 
                 1.30 
                 1.91 
                 1.33 
                 1.30 
                 1.91 
               
               
                 p Value 
                 0.51 
                 0.64 
                 0.31 
                 0.60 
                 0.64 
                 0.39 
                 0.60 
                 0.64 
                 0.39 
               
               
                 Lower limit of 95% CI 
                 0.497 
                 0.441 
                 0.495 
                 0.463 
                 0.441 
                 0.440 
                 0.463 
                 0.441 
                 0.440 
               
               
                 Upper limit of 95% CI 
                 4.09 
                 3.80 
                 9.27 
                 3.80 
                 3.80 
                 8.29 
                 3.80 
                 3.80 
                 8.29 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “recovered” and “non-recovered” cohorts where 
               
               
                 recovery starts within 7 days after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE 
               
               
                 criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 247 
                 255 
                 246 
                 255 
                 246 
                 255 
               
               
                 Average 
                 249 
                 296 
                 249 
                 294 
                 249 
                 294 
               
               
                 Stdev 
                 108 
                 144 
                 110 
                 140 
                 110 
                 140 
               
               
                 p (t-test) 
                   
                 0.14 
                   
                 0.14 
                   
                 0.14 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 592 
                 651 
                 592 
                 651 
                 592 
                 651 
               
               
                 n (Patient) 
                 54 
                 30 
                 52 
                 32 
                 52 
                 32 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 255 
                 221 
                 256 
                 224 
                 256 
                 224 
               
               
                 Average 
                 263 
                 271 
                 263 
                 270 
                 263 
                 270 
               
               
                 Stdev 
                 120 
                 129 
                 121 
                 127 
                 121 
                 127 
               
               
                 p (t-test) 
                   
                 0.81 
                   
                 0.84 
                   
                 0.84 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 651 
                 590 
                 651 
                 590 
                 651 
                 590 
               
               
                 n (Patient) 
                 59 
                 22 
                 58 
                 23 
                 58 
                 23 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 248 
                 249 
                 248 
                 249 
                 249 
                 249 
               
               
                 Average 
                 253 
                 290 
                 247 
                 293 
                 248 
                 291 
               
               
                 Stdev 
                 107 
                 145 
                 94.9 
                 147 
                 95.4 
                 146 
               
               
                 p (t-test) 
                   
                 0.21 
                   
                 0.11 
                   
                 0.14 
               
               
                 Min 
                 73.7 
                 105 
                 73.7 
                 105 
                 73.7 
                 105 
               
               
                 Max 
                 559 
                 651 
                 429 
                 651 
                 429 
                 651 
               
               
                 n (Patient) 
                 40 
                 38 
                 42 
                 36 
                 41 
                 37 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or  
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.50 
                 0.55 
                 0.58 
                 0.50 
                 0.56 
                 0.58 
                 0.50 
                 0.56 
               
               
                 SE 
                 0.066 
                 0.073 
                 0.065 
                 0.065 
                 0.072 
                 0.066 
                 0.065 
                 0.072 
                 0.065 
               
               
                 p Value 
                 0.25 
                 0.96 
                 0.43 
                 0.24 
                 0.97 
                 0.33 
                 0.24 
                 0.97 
                 0.38 
               
               
                 nCohort Recovered 
                 54 
                 59 
                 40 
                 52 
                 58 
                 42 
                 52 
                 58 
                 41 
               
               
                 nCohort Non-recovered 
                 30 
                 22 
                 38 
                 32 
                 23 
                 36 
                 32 
                 23 
                 37 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 172 
                 169 
                 171 
                 172 
                 169 
                 171 
                 172 
               
               
                 Sensitivity 
                 80% 
                 77% 
                 79% 
                 81% 
                 78% 
                 78% 
                 81% 
                 78% 
                 78% 
               
               
                 Specificity 
                 28% 
                 27% 
                 30% 
                 29% 
                 28% 
                 29% 
                 29% 
                 28% 
                 29% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 53% 
                 41% 
                 50% 
                 53% 
                 39% 
                 50% 
                 53% 
                 39% 
                 51% 
               
               
                 Specificity 
                 52% 
                 47% 
                 50% 
                 52% 
                 47% 
                 50% 
                 52% 
                 47% 
                 51% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 334 
                 332 
                 331 
                 334 
                 332 
                 331 
                 334 
               
               
                 Sensitivity 
                 30% 
                 27% 
                 29% 
                 28% 
                 26% 
                 31% 
                 28% 
                 26% 
                 30% 
               
               
                 Specificity 
                 78% 
                 76% 
                 78% 
                 77% 
                 76% 
                 79% 
                 77% 
                 76% 
                 78% 
               
               
                 OR Quartile 2 
                 1.54 
                 1.27 
                 1.61 
                 1.76 
                 1.37 
                 1.40 
                 1.76 
                 1.37 
                 1.50 
               
               
                 p Value 
                 0.43 
                 0.69 
                 0.37 
                 0.30 
                 0.59 
                 0.52 
                 0.30 
                 0.59 
                 0.44 
               
               
                 Lower limit of 95% CI 
                 0.525 
                 0.400 
                 0.572 
                 0.602 
                 0.436 
                 0.499 
                 0.602 
                 0.436 
                 0.534 
               
               
                 Upper limit of 95% CI 
                 4.51 
                 4.00 
                 4.51 
                 5.13 
                 4.31 
                 3.93 
                 5.13 
                 4.31 
                 4.21 
               
               
                 OR Quartile 3 
                 1.23 
                 0.625 
                 1.00 
                 1.22 
                 0.560 
                 1.00 
                 1.22 
                 0.560 
                 1.11 
               
               
                 p Value 
                 0.65 
                 0.35 
                 1.0 
                 0.65 
                 0.25 
                 1.0 
                 0.65 
                 0.25 
                 0.82 
               
               
                 Lower limit of 95% CI 
                 0.503 
                 0.232 
                 0.411 
                 0.507 
                 0.209 
                 0.411 
                 0.507 
                 0.209 
                 0.456 
               
               
                 Upper limit of 95% CI 
                 3.01 
                 1.69 
                 2.43 
                 2.96 
                 1.50 
                 2.44 
                 2.96 
                 1.50 
                 2.70 
               
               
                 OR Quartile 4 
                 1.50 
                 1.21 
                 1.40 
                 1.30 
                 1.11 
                 1.61 
                 1.30 
                 1.11 
                 1.50 
               
               
                 p Value 
                 0.43 
                 0.74 
                 0.52 
                 0.60 
                 0.85 
                 0.36 
                 0.60 
                 0.85 
                 0.43 
               
               
                 Lower limit of 95% CI 
                 0.546 
                 0.396 
                 0.506 
                 0.477 
                 0.366 
                 0.580 
                 0.477 
                 0.366 
                 0.542 
               
               
                 Upper limit of 95% CI 
                 4.12 
                 3.67 
                 3.90 
                 3.56 
                 3.36 
                 4.49 
                 3.56 
                 3.36 
                 4.18 
               
               
                   
               
            
           
         
       
     
     Example 8. Use of C-C Motif Chemokine 16 for Evaluating Renal Status in Patients Admitted to the ICU: Recovery to RIFLE 0 from RIFLE I and F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 16 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output during a period starting at 12, 24, 48, or 72 hours after sample collection or at any time within 7 days after sample collection. Two cohorts are defined to represent a “recovered” and a “non-recovered” population. “Recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0). “Non-recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is risk of injury (R), injury (I) or failure (F). If a patient dies or is placed on renal replacement therapy (RRT) within 9 days of enrollment, the patient is considered “non-recovered”. 
     The ability to distinguish the “recovered” and “non-recovered” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 8.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.00821 
                 0.0173 
                 0.0120 
                 0.0157 
                 0.0120 
                 0.0157 
               
               
                 Average 
                 0.0135 
                 0.0735 
                 0.0153 
                 0.0717 
                 0.0167 
                 0.0702 
               
               
                 Stdev 
                 0.0140 
                 0.346 
                 0.0158 
                 0.342 
                 0.0171 
                 0.338 
               
               
                 p (t-test) 
                   
                 0.15 
                   
                 0.17 
                   
                 0.18 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 7.74E−6 
                 4.13E−6 
               
               
                 Max 
                 0.0427 
                 2.98 
                 0.0427 
                 2.98 
                 0.0427 
                 2.98 
               
               
                 n (Patient) 
                 8 
                 73 
                 6 
                 75 
                 4 
                 77 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.00821 
                 0.0225 
                 0.00715 
                 0.0208 
                 0.0122 
                 0.0182 
               
               
                 Average 
                 0.0157 
                 0.0981 
                 0.0162 
                 0.0947 
                 0.0173 
                 0.0913 
               
               
                 Stdev 
                 0.0223 
                 0.412 
                 0.0230 
                 0.404 
                 0.0236 
                 0.397 
               
               
                 p (t-test) 
                   
                 0.16 
                   
                 0.17 
                   
                 0.18 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 30 
                 51 
                 28 
                 53 
                 26 
                 55 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0213 
                 0.0181 
                 0.0231 
                 0.0177 
                 0.0213 
                 0.0177 
               
               
                 Average 
                 0.0368 
                 0.0809 
                 0.0405 
                 0.0797 
                 0.0422 
                 0.0776 
               
               
                 Stdev 
                 0.0475 
                 0.378 
                 0.0483 
                 0.375 
                 0.0506 
                 0.369 
               
               
                 p (t-test) 
                   
                 0.39 
                   
                 0.44 
                   
                 0.48 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 11 
                 61 
                 10 
                 62 
                 9 
                 64 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or  
                 sCr 
                 UO 
                 sCr or  
                 sCr 
                 UO 
                 sCr or  
                 sCr 
                 UO 
               
               
                 Duration (hr) 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.61 
                 0.68 
                 0.49 
                 0.59 
                 0.67 
                 0.45 
                 0.56 
                 0.64 
                 0.44 
               
               
                 SE 
                 0.098 
                 0.060 
                 0.095 
                 0.11 
                 0.061 
                 0.096 
                 0.14 
                 0.064 
                 0.100 
               
               
                 p Value 
                 0.26 
                 0.0033 
                 0.94 
                 0.41 
                 0.0067 
                 0.57 
                 0.70 
                 0.030 
                 0.57 
               
               
                 nCohort Recovered 
                 8 
                 30 
                 11 
                 6 
                 28 
                 10 
                 4 
                 26 
                 9 
               
               
                 nCohort Non- 
                 73 
                 51 
                 61 
                 75 
                 53 
                 62 
                 77 
                 55 
                 64 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00161 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 Sensitivity 
                 71% 
                 78% 
                 74% 
                 72% 
                 79% 
                 71% 
                 71% 
                 78% 
                 70% 
               
               
                 Specificity 
                 25% 
                 40% 
                 18% 
                 33% 
                 43% 
                 10% 
                 25% 
                 42% 
                 11% 
               
               
                 Cutoff Quartile 3 
                 0.0157 
                 0.0157 
                 0.0193 
                 0.0157 
                 0.0157 
                 0.0193 
                 0.0157 
                 0.0157 
                 0.0181 
               
               
                 Sensitivity 
                 51% 
                 59% 
                 49% 
                 49% 
                 57% 
                 48% 
                 49% 
                 55% 
                 48% 
               
               
                 Specificity 
                 62% 
                 67% 
                 45% 
                 50% 
                 64% 
                 40% 
                 50% 
                 62% 
                 44% 
               
               
                 Cutoff Quartile 4 
                 0.0427 
                 0.0427 
                 0.0464 
                 0.0427 
                 0.0427 
                 0.0464 
                 0.0427 
                 0.0427 
                 0.0460 
               
               
                 Sensitivity 
                 27% 
                 35% 
                 26% 
                 27% 
                 34% 
                 26% 
                 26% 
                 33% 
                 25% 
               
               
                 Specificity 
                 100% 
                 93% 
                 82% 
                 100% 
                 93% 
                 80% 
                 100% 
                 92% 
                 78% 
               
               
                 OR Quartile 2 
                 0.825 
                 2.42 
                 0.625 
                 1.29 
                 2.86 
                 0.272 
                 0.833 
                 2.63 
                 0.296 
               
               
                 p Value 
                 0.82 
                 0.079 
                 0.57 
                 0.78 
                 0.039 
                 0.23 
                 0.88 
                 0.060 
                 0.27 
               
               
                 Lower limit of  
                 0.154 
                 0.901 
                 0.122 
                 0.219 
                 1.05 
                 0.0320 
                 0.0822 
                 0.960 
                 0.0346 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 4.42 
                 6.52 
                 3.21 
                 7.55 
                 7.79 
                 2.30 
                 8.45 
                 7.20 
                 2.53 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.71 
                 2.86 
                 0.806 
                 0.974 
                 2.35 
                 0.625 
                 0.974 
                 1.92 
                 0.752 
               
               
                 p Value 
                 0.48 
                 0.029 
                 0.74 
                 0.97 
                 0.077 
                 0.50 
                 0.98 
                 0.18 
                 0.69 
               
               
                 Lower limit of  
                 0.381 
                 1.11 
                 0.222 
                 0.185 
                 0.913 
                 0.160 
                 0.131 
                 0.741 
                 0.185 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 7.70 
                 7.33 
                 2.93 
                 5.14 
                 6.04 
                 2.43 
                 7.27 
                 4.97 
                 3.06 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 6.51 
                 7.64 
                 1.60 
                 4.80 
                 6.69 
                 1.39 
                 3.21 
                 5.84 
                 1.17 
               
               
                 p Value 
                 0.20 
                 0.0099 
                 0.57 
                 0.29 
                 0.016 
                 0.69 
                 0.44 
                 0.026 
                 0.86 
               
               
                 Lower limit of 
                 0.359 
                 1.63 
                 0.312 
                 0.259 
                 1.42 
                 0.267 
                 0.165 
                 1.24 
                 0.220 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 118 
                 35.8 
                 8.21 
                 89.1 
                 31.4 
                 7.25 
                 62.2 
                 27.5 
                 6.20 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0151 
                 0.0173 
                 0.0209 
                 0.0155 
                 0.0206 
                 0.0157 
               
               
                 Average 
                 0.0159 
                 0.0768 
                 0.0207 
                 0.0737 
                 0.0201 
                 0.0730 
               
               
                 Stdev 
                 0.0128 
                 0.356 
                 0.0115 
                 0.349 
                 0.0122 
                 0.347 
               
               
                 p (t-test) 
                   
                 0.16 
                   
                 0.21 
                   
                 0.20 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 0.00279 
                 4.13E−6 
                 0.00279 
                 4.13E−6 
               
               
                 Max 
                 0.0427 
                 2.98 
                 0.0427 
                 2.98 
                 0.0427 
                 2.98 
               
               
                 n (Patient) 
                 11 
                 69 
                 8 
                 72 
                 7 
                 73 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.00908 
                 0.0225 
                 0.0122 
                 0.0195 
                 0.0122 
                 0.0195 
               
               
                 Average 
                 0.0159 
                 0.102 
                   
                   
                   
                   
               
               
                 Stdev 
                 0.0222 
                 0.420 
                 0.0231 
                 0.408 
                 0.0231 
                 0.408 
               
               
                 p (t-test) 
                   
                 0.16 
                   
                 0.17 
                   
                 0.17 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 31 
                 49 
                 28 
                 52 
                 28 
                 52 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0209 
                 0.0190 
                 0.0213 
                 0.0173 
                 0.0209 
                 0.0173 
               
               
                 Average 
                 0.0366 
                 0.0881 
                 0.0395 
                 0.0866 
                 0.0407 
                 0.0840 
               
               
                 Stdev 
                 0.0417 
                 0.401 
                 0.0419 
                 0.398 
                 0.0434 
                 0.391 
               
               
                 p (t-test) 
                   
                 0.36 
                   
                 0.40 
                   
                 0.42 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 0.00856 
                 4.13E−6 
                 0.00856 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 14 
                 54 
                 13 
                 55 
                 12 
                 57 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or  
                   
                   
                 sCr or  
                   
                   
                 sCr or  
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.69 
                 0.44 
                 0.47 
                 0.65 
                 0.40 
                 0.48 
                 0.65 
                 0.39 
               
               
                 SE 
                 0.090 
                 0.059 
                 0.084 
                 0.11 
                 0.062 
                 0.084 
                 0.11 
                 0.062 
                 0.085 
               
               
                 p Value 
                 0.40 
                 0.0016 
                 0.49 
                 0.76 
                 0.013 
                 0.23 
                 0.85 
                 0.013 
                 0.20 
               
               
                 nCohort  
                 11 
                 31 
                 14 
                 8 
                 28 
                 13 
                 7 
                 28 
                 12 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Non- 
                 69 
                 49 
                 54 
                 72 
                 52 
                 55 
                 73 
                 52 
                 57 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00161 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 Sensitivity 
                 71% 
                 82% 
                 70% 
                 69% 
                 81% 
                 67% 
                 70% 
                 81% 
                 67% 
               
               
                 Specificity 
                 18% 
                 42% 
                 7% 
                 0% 
                 43% 
                 0% 
                 0% 
                 43% 
                 0% 
               
               
                 Cutoff Quartile 3 
                 0.0165 
                 0.0165 
                 0.0207 
                 0.0165 
                 0.0165 
                 0.0207 
                 0.0165 
                 0.0165 
                 0.0206 
               
               
                 Sensitivity 
                 51% 
                 59% 
                 50% 
                 49% 
                 56% 
                 49% 
                 49% 
                 56% 
                 49% 
               
               
                 Specificity 
                 55% 
                 65% 
                 50% 
                 38% 
                 61% 
                 46% 
                 43% 
                 61% 
                 50% 
               
               
                 Cutoff Quartile 4 
                 0.0435 
                 0.0435 
                 0.0464 
                 0.0435 
                 0.0435 
                 0.0464 
                 0.0435 
                 0.0435 
                 0.0460 
               
               
                 Sensitivity 
                 29% 
                 37% 
                 26% 
                 28% 
                 35% 
                 25% 
                 27% 
                 35% 
                 25% 
               
               
                 Specificity 
                 100% 
                 94% 
                 79% 
                 100% 
                 93% 
                 77% 
                 100% 
                 93% 
                 75% 
               
               
                 OR Quartile 2 
                 0.544 
                 3.21 
                 0.183 
                 0.132 
                 3.15 
                 0.0751 
                 0.153 
                 3.15 
                 0.0790 
               
               
                 p Value 
                 0.46 
                 0.024 
                 0.12 
                 0.17 
                 0.027 
                 0.078 
                 0.20 
                 0.027 
                 0.084 
               
               
                 Lower limit of 
                 0.108 
                 1.16 
                 0.0220 
                 0.00730 
                 1.14 
                 0.00423 
                 0.00835 
                 1.14 
                 0.00444 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 2.75 
                 8.86 
                 1.52 
                 2.39 
                 8.72 
                 1.33 
                 2.79 
                 8.72 
                 1.41 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.24 
                 2.64 
                 1.00 
                 0.568 
                 1.95 
                 0.827 
                 0.730 
                 1.95 
                 0.966 
               
               
                 p Value 
                 0.75 
                 0.041 
                 1.0 
                 0.46 
                 0.16 
                 0.76 
                 0.69 
                 0.16 
                 0.96 
               
               
                 Lower limit of  
                 0.344 
                 1.04 
                 0.309 
                 0.126 
                 0.765 
                 0.246 
                 0.152 
                 0.765 
                 0.278 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 4.43 
                 6.69 
                 3.24 
                 2.55 
                 4.96 
                 2.78 
                 3.49 
                 4.96 
                 3.35 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 9.53 
                 8.42 
                 1.28 
                 6.64 
                 6.88 
                 1.14 
                 5.75 
                 6.88 
                 0.977 
               
               
                 p Value 
                 0.12 
                 0.0069 
                 0.73 
                 0.20 
                 0.015 
                 0.86 
                 0.24 
                 0.015 
                 0.97 
               
               
                 Lower limit of  
                 0.536 
                 1.79 
                 0.312 
                 0.366 
                 1.46 
                 0.274 
                 0.314 
                 1.46 
                 0.232 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of  
                 169 
                 39.5 
                 5.28 
                 120 
                 32.3 
                 4.74 
                 105 
                 32.3 
                 4.12 
               
               
                 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery 
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0157 
                 0.0173 
                 0.0157 
                 0.0173 
                 0.0157 
                 0.0173 
               
               
                 Average 
                 0.0210 
                 0.0875 
                 0.0218 
                 0.0850 
                 0.0218 
                 0.0850 
               
               
                 Stdev 
                 0.0231 
                 0.391 
                 0.0237 
                 0.384 
                 0.0237 
                 0.384 
               
               
                 p (t-test) 
                   
                 0.21 
                   
                 0.22 
                   
                 0.22 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 23 
                 57 
                 21 
                 59 
                 21 
                 59 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0146 
                 0.0208 
                 0.0142 
                 0.0217 
                 0.0142 
                 0.0217 
               
               
                 Average 
                 0.0183 
                 0.106 
                 0.0174 
                 0.105 
                 0.0174 
                 0.105 
               
               
                 Stdev 
                 0.0227 
                 0.438 
                 0.0224 
                 0.433 
                 0.0224 
                 0.433 
               
               
                 p (t-test) 
                   
                 0.19 
                   
                 0.18 
                   
                 0.18 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 34 
                 45 
                 33 
                 46 
                 33 
                 46 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0227 
                 0.0208 
                 0.0227 
                 0.0190 
                 0.0227 
                 0.0190 
               
               
                 Average 
                 0.0348 
                 0.116 
                 0.0368 
                 0.108 
                 0.0368 
                 0.108 
               
               
                 Stdev 
                 0.0385 
                 0.481 
                 0.0397 
                 0.464 
                 0.0397 
                 0.464 
               
               
                 p (t-test) 
                   
                 0.32 
                   
                 0.34 
                   
                 0.34 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 22 
                 37 
                 20 
                 40 
                 20 
                 40 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Period 
                 sCr or  
                 sCr 
                 UO 
                 sCr or  
                 sCr 
                 UO 
                 sCr or  
                 sCr  
                 UO 
               
               
                 Duration (hr) 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.54 
                 0.63 
                 0.46 
                 0.52 
                 0.65 
                 0.43 
                 0.52 
                 0.65 
                 0.43 
               
               
                 SE 
                 0.071 
                 0.062 
                 0.078 
                 0.073 
                 0.062 
                 0.078 
                 0.073 
                 0.062 
                 0.078 
               
               
                 p Value 
                 0.58 
                 0.032 
                 0.60 
                 0.77 
                 0.016 
                 0.38 
                 0.77 
                 0.016 
                 0.38 
               
               
                 nCohort  
                 23 
                 34 
                 22 
                 21 
                 33 
                 20 
                 21 
                 33 
                 20 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Non- 
                 57 
                 45 
                 37 
                 59 
                 46 
                 40 
                 59 
                 46 
                 40 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quar- 
                 0.00202 
                 0.00202 
                 0.00393 
                 0.00202 
                 0.00202 
                 0.00260 
                 0.00202 
                 0.00202 
                 0.00260 
               
               
                 tile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 70% 
                 80% 
                 65% 
                 69% 
                 80% 
                 68% 
                 69% 
                 80% 
                 68% 
               
               
                 Specificity 
                 22% 
                 38% 
                 9% 
                 19% 
                 39% 
                 10% 
                 19% 
                 39% 
                 10% 
               
               
                 Cutoff Quar- 
                 0.0165 
                 0.0157 
                 0.0208 
                 0.0165 
                 0.0157 
                 0.0207 
                 0.0165 
                 0.0157 
                 0.0207 
               
               
                 tile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 51% 
                 56% 
                 49% 
                 51% 
                 57% 
                 50% 
                 51% 
                 57% 
                 50% 
               
               
                 Specificity 
                 52% 
                 59% 
                 50% 
                 52% 
                 61% 
                 50% 
                 52% 
                 61% 
                 50% 
               
               
                 Cutoff Quar- 
                 0.0435 
                 0.0427 
                 0.0467 
                 0.0435 
                 0.0427 
                 0.0464 
                 0.0435 
                 0.0427 
                 0.0464 
               
               
                 tile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 32% 
                 33% 
                 27% 
                 31% 
                 35% 
                 25% 
                 31% 
                 35% 
                 25% 
               
               
                 Specificity 
                 91% 
                 88% 
                 77% 
                 90% 
                 91% 
                 75% 
                 90% 
                 91% 
                 75% 
               
               
                 OR Quartile 2 
                 0.654 
                 2.48 
                 0.185 
                 0.536 
                 2.67 
                 0.231 
                 0.536 
                 2.67 
                 0.231 
               
               
                 p Value 
                 0.47 
                 0.077 
                 0.039 
                 0.32 
                 0.056 
                 0.073 
                 0.32 
                 0.056 
                 0.073 
               
               
                 Lower limit  
                 0.209 
                 0.906 
                 0.0372 
                 0.158 
                 0.974 
                 0.0464 
                 0.158 
                 0.974 
                 0.0464 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 2.05 
                 6.77 
                 0.917 
                 1.82 
                 7.33 
                 1.15 
                 1.82 
                 7.33 
                 1.15 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.13 
                 1.79 
                 0.947 
                 1.14 
                 2.00 
                 1.00 
                 1.14 
                 2.00 
                 1.00 
               
               
                 p Value 
                 0.80 
                 0.21 
                 0.92 
                 0.80 
                 0.14 
                 1.0 
                 0.80 
                 0.14 
                 1.0 
               
               
                 Lower limit  
                 0.429 
                 0.725 
                 0.330 
                 0.420 
                 0.805 
                 0.342 
                 0.420 
                 0.805 
                 0.342 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 2.98 
                 4.40 
                 2.72 
                 3.08 
                 4.97 
                 2.93 
                 3.08 
                 4.97 
                 2.93 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 4.85 
                 3.75 
                 1.26 
                 4.17 
                 5.33 
                 1.00 
                 4.17 
                 5.33 
                 1.00 
               
               
                 p Value 
                 0.047 
                 0.033 
                 0.71 
                 0.073 
                 0.014 
                 1.0 
                 0.073 
                 0.014 
                 1.0 
               
               
                 Lower limit  
                 1.02 
                 1.11 
                 0.367 
                 0.877 
                 1.41 
                 0.289 
                 0.877 
                 1.41 
                 0.289 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 22.9 
                 12.6 
                 4.32 
                 19.8 
                 20.2 
                 3.45 
                 19.8 
                 20.2 
                 3.45 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0152 
                 0.0182 
                 0.0153 
                 0.0177 
                 0.0153 
                 0.0177 
               
               
                 Average 
                 0.0216 
                 0.0915 
                 0.0225 
                 0.0898 
                 0.0225 
                 0.0898 
               
               
                 Stdev 
                 0.0287 
                 0.405 
                 0.0290 
                 0.401 
                 0.0290 
                 0.401 
               
               
                 p (t-test) 
                   
                 0.22 
                   
                 0.23 
                   
                 0.23 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.113 
                 2.98 
                 0.113 
                 2.98 
                 0.113 
                 2.98 
               
               
                 n (Patient) 
                 26 
                 53 
                 25 
                 54 
                 25 
                 54 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0151 
                 0.0177 
                 0.0146 
                 0.0182 
                 0.0152 
                 0.0173 
               
               
                 Average 
                 0.0191 
                 0.108 
                 0.0179 
                 0.107 
                 0.0190 
                 0.102 
               
               
                 Stdev 
                 0.0229 
                 0.453 
                 0.0220 
                 0.448 
                 0.0222 
                 0.438 
               
               
                 p (t-test) 
                   
                 0.22 
                   
                 0.20 
                   
                 0.21 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 35 
                 42 
                 34 
                 43 
                 32 
                 45 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0293 
                 0.0225 
                 0.0296 
                 0.0217 
                 0.0296 
                 0.0217 
               
               
                 Average 
                 0.0427 
                 0.122 
                 0.0453 
                 0.118 
                 0.0453 
                 0.118 
               
               
                 Stdev 
                 0.0434 
                 0.494 
                 0.0434 
                 0.488 
                 0.0434 
                 0.488 
               
               
                 p (t-test) 
                   
                 0.36 
                   
                 0.39 
                   
                 0.39 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 17 
                 35 
                 16 
                 36 
                 16 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or  
                 sCr 
                 UO 
                 sCr or 
                 sCr 
                 UO 
                 sCr or 
                 sCr 
                 UO 
               
               
                 Duration (hr) 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.60 
                 0.45 
                 0.56 
                 0.62 
                 0.41 
                 0.56 
                 0.58 
                 0.41 
               
               
                 SE 
                 0.067 
                 0.064 
                 0.085 
                 0.069 
                 0.064 
                 0.084 
                 0.069 
                 0.066 
                 0.084 
               
               
                 p Value 
                 0.21 
                 0.11 
                 0.55 
                 0.37 
                 0.056 
                 0.29 
                 0.37 
                 0.23 
                 0.29 
               
               
                 nCohort  
                 26 
                 35 
                 17 
                 25 
                 34 
                 16 
                 25 
                 32 
                 16 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Non- 
                 53 
                 42 
                 35 
                 54 
                 43 
                 36 
                 54 
                 45 
                 36 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00449 
                 0.00202 
                 0.00202 
                 0.00449 
                 0.00202 
                 0.00202 
                 0.00449 
               
               
                 Sensitivity 
                 74% 
                 79% 
                 71% 
                 72% 
                 79% 
                 69% 
                 72% 
                 76% 
                 69% 
               
               
                 Specificity 
                 31% 
                 37% 
                 18% 
                 28% 
                 38% 
                 12% 
                 28% 
                 34% 
                 12% 
               
               
                 Cutoff Quartile 3 
                 0.0157 
                 0.0153 
                 0.0237 
                 0.0157 
                 0.0153 
                 0.0237 
                 0.0157 
                 0.0153 
                 0.0237 
               
               
                 Sensitivity 
                 53% 
                 52% 
                 49% 
                 52% 
                 53% 
                 47% 
                 52% 
                 51% 
                 47% 
               
               
                 Specificity 
                 58% 
                 54% 
                 47% 
                 56% 
                 56% 
                 44% 
                 56% 
                 53% 
                 44% 
               
               
                 Cutoff Quartile 4 
                 0.0427 
                 0.0411 
                 0.0494 
                 0.0427 
                 0.0411 
                 0.0494 
                 0.0427 
                 0.0411 
                 0.0494 
               
               
                 Sensitivity 
                 30% 
                 31% 
                 23% 
                 30% 
                 33% 
                 22% 
                 30% 
                 31% 
                 22% 
               
               
                 Specificity 
                 88% 
                 83% 
                 71% 
                 88% 
                 85% 
                 69% 
                 88% 
                 84% 
                 69% 
               
               
                 OR Quartile 2 
                 1.24 
                 2.17 
                 0.536 
                 1.01 
                 2.34 
                 0.325 
                 1.01 
                 1.62 
                 0.325 
               
               
                 p Value 
                 0.69 
                 0.13 
                 0.40 
                 0.98 
                 0.099 
                 0.18 
                 0.98 
                 0.34 
                 0.18 
               
               
                 Lower limit of 
                 0.441 
                 0.792 
                 0.126 
                 0.351 
                 0.853 
                 0.0628 
                 0.351 
                 0.597 
                 0.0628 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 3.48 
                 5.93 
                 2.28 
                 2.91 
                 6.42 
                 1.68 
                 2.91 
                 4.39 
                 1.68 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                 1.53 
                 1.31 
                 0.840 
                 1.37 
                 1.46 
                 0.696 
                 1.37 
                 1.18 
                 0.696 
               
               
                 p Value 
                 0.38 
                 0.56 
                 0.77 
                 0.52 
                 0.41 
                 0.55 
                 0.52 
                 0.71 
                 0.55 
               
               
                 Lower limit of 
                 0.593 
                 0.531 
                 0.263 
                 0.528 
                 0.590 
                 0.213 
                 0.528 
                 0.478 
                 0.213 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 3.94 
                 3.21 
                 2.68 
                 3.56 
                 3.60 
                 2.28 
                 3.56 
                 2.94 
                 2.28 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 3.32 
                 2.17 
                 0.711 
                 3.09 
                 2.80 
                 0.629 
                 3.09 
                 2.44 
                 0.629 
               
               
                 p Value 
                 0.079 
                 0.17 
                 0.61 
                 0.099 
                 0.078 
                 0.49 
                 0.099 
                 0.13 
                 0.49 
               
               
                 Lower limit of 
                 0.869 
                 0.724 
                 0.192 
                 0.808 
                 0.892 
                 0.168 
                 0.808 
                 0.777 
                 0.168 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit of 
                 12.6 
                 6.48 
                 2.63 
                 11.8 
                 8.79 
                 2.35 
                 11.8 
                 7.66 
                 2.35 
               
               
                 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 within 7 days after sample collection and renal status is assessed by serum creatinine 
               
               
                 (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery 
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0151 
                 0.0177 
                 0.0153 
                 0.0171 
                 0.0153 
                 0.0171 
               
               
                 Average 
                 0.0265 
                 0.105  
                 0.0250 
                 0.0996 
                 0.0254 
                 0.0961 
               
               
                 Stdev 
                 0.0352 
                 0.453  
                 0.0302 
                 0.434  
                 0.0309 
                 0.425  
               
               
                 p (t-test) 
                   
                 0.27   
                   
                 0.26   
                   
                 0.26   
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151  
                 2.98   
                 0.113  
                 2.98   
                 0.113  
                 2.98   
               
               
                 n (Patient) 
                 41    
                 42    
                 37       
                 46      
                 35      
                 48      
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0152 
                 0.0182 
                 0.0152 
                 0.0182 
                 0.0155 
                 0.0173 
               
               
                 Average 
                 0.0268 
                 0.127  
                 0.0245 
                 0.124  
                 0.0254 
                 0.113  
               
               
                 Stdev 
                 0.0341 
                 0.509  
                 0.0294 
                 0.494  
                 0.0301 
                 0.469  
               
               
                 p (t-test) 
                   
                 0.27   
                   
                 0.25   
                   
                 0.26   
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151  
                 2.98   
                 0.113  
                 2.98   
                 0.113  
                 2.98   
               
               
                 n (Patient) 
                 48    
                 33      
                 46      
                 35      
                 42      
                 39      
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0206 
                 0.0150 
                 0.0181 
                 0.0150 
                 0.0169 
                 0.0151 
               
               
                 Average 
                 0.0322 
                 0.0925 
                 0.0297 
                 0.0933 
                 0.0299 
                 0.0919 
               
               
                 Stdev 
                 0.0413 
                 0.425  
                 0.0365 
                 0.425  
                 0.0371 
                 0.421  
               
               
                 p (t-test) 
                   
                 0.34   
                   
                 0.31   
                   
                 0.31   
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.191  
                 2.98   
                 0.151  
                 2.98   
                 0.151  
                 2.98   
               
               
                 n (Patient) 
                 31    
                 48      
                 31      
                 48      
                 30      
                 49      
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Period 
                 sCr or  
                 sCr 
                 UO 
                 sCr or 
                 sCr 
                 UO 
                 sCr or  
                 sCr 
                 UO 
               
               
                 Duration (hr) 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
                 UO 
                 only 
                 only 
               
               
                   
               
               
                 AUC 
                 0.57 
                 0.57 
                 0.47 
                 0.55 
                 0.58 
                 0.49 
                 0.55 
                 0.56 
                 0.50 
               
               
                 SE 
                 0.063 
                 0.066 
                 0.067 
                 0.063 
                 0.065 
                 0.067 
                 0.064 
                 0.064 
                 0.067 
               
               
                 p Value 
                 0.27 
                 0.31 
                 0.67 
                 0.39 
                 0.21 
                 0.88 
                 0.39 
                 0.37 
                 0.94 
               
               
                 nCohort  
                 41 
                 48 
                 31 
                 37 
                 46 
                 31 
                 35 
                 42 
                 30 
               
               
                 Recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Non- 
                 42 
                 33 
                 48 
                 46 
                 35 
                 48 
                 48 
                 39 
                 49 
               
               
                 recovered 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quar- 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 tile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 76% 
                 79% 
                 69% 
                 76% 
                 80% 
                 69% 
                 77% 
                 79% 
                 69% 
               
               
                 Specificity 
                 32% 
                 33% 
                 23% 
                 32% 
                 35% 
                 23% 
                 34% 
                 36% 
                 23% 
               
               
                 Cutoff Quar- 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
               
               
                 tile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 55% 
                 55% 
                 46% 
                 52% 
                 54% 
                 48% 
                 52% 
                 51% 
                 49% 
               
               
                 Specificity 
                 56% 
                 54% 
                 45% 
                 54% 
                 54% 
                 48% 
                 54% 
                 52% 
                 50% 
               
               
                 Cutoff Quar- 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
               
               
                 tile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 26% 
                 27% 
                 23% 
                 26% 
                 29% 
                 25% 
                 25% 
                 28% 
                 24% 
               
               
                 Specificity 
                 78% 
                 77% 
                 74% 
                 78% 
                 78% 
                 77% 
                 77% 
                 79% 
                 77% 
               
               
                 OR Quar- 
                 1.49 
                 1.86 
                 0.642 
                 1.53 
                 2.13 
                 0.642 
                 1.75 
                 2.15 
                 0.690 
               
               
                 tile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.42 
                 0.24 
                 0.40 
                 0.39 
                 0.15 
                 0.40 
                 0.26 
                 0.13 
                 0.48 
               
               
                 Lower limit  
                 0.564 
                 0.664 
                 0.227 
                 0.581 
                 0.764 
                 0.227 
                 0.666 
                 0.791 
                 0.243 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 3.91 
                 5.19 
                 1.82 
                 4.01 
                 5.96 
                 1.82 
                 4.63 
                 5.86 
                 1.95 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quar- 
                 1.55 
                 1.42 
                 0.697 
                 1.28 
                 1.41 
                 0.862 
                 1.29 
                 1.16 
                 0.960 
               
               
                 tile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.32 
                 0.44 
                 0.44 
                 0.57 
                 0.44 
                 0.75 
                 0.57 
                 0.74 
                 0.93 
               
               
                 Lower limit 
                 0.651 
                 0.582 
                 0.281 
                 0.539 
                 0.585 
                 0.349 
                 0.539 
                 0.484 
                 0.387 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 3.68 
                 3.45 
                 1.73 
                 3.06 
                 3.42 
                 2.13 
                 3.09 
                 2.77 
                 2.38 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quar- 
                 1.26 
                 1.26 
                 0.855 
                 1.28 
                 1.44 
                 1.14 
                 1.12 
                 1.44 
                 1.07 
               
               
                 tile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.65 
                 0.66 
                 0.77 
                 0.64 
                 0.48 
                 0.81 
                 0.82 
                 0.48 
                 0.91 
               
               
                 Lower limit  
                 0.460 
                 0.455 
                 0.299 
                 0.460 
                 0.522 
                 0.394 
                 0.404 
                 0.522 
                 0.366 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 3.46 
                 3.50 
                 2.44 
                 3.56 
                 3.97 
                 3.32 
                 3.13 
                 3.97 
                 3.10 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.48 
                 9.96 
                 8.41 
                 10.0 
                 8.48 
                 9.96 
               
               
                 Average 
                 8.83 
                 12.4 
                 6.73 
                 12.4 
                 8.01 
                 12.3 
               
               
                 Stdev 
                 4.38 
                 8.96 
                 2.95 
                 8.82 
                 1.64 
                 8.85 
               
               
                 p (t-test) 
                   
                 0.090 
                   
                 0.012 
                   
                 0.0088 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 5.31 
                 1.32 
               
               
                 Max 
                 15.9 
                 38.9 
                 9.75 
                 38.9 
                 9.75 
                 38.9 
               
               
                 n (Patient) 
                 8 
                 74 
                 5 
                 77 
                 4 
                 78 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.90 
                 10.6 
                 7.72 
                 10.9 
                 7.90 
                 10.6 
               
               
                 Average 
                 9.48 
                 13.8 
                 9.08 
                 13.8 
                 9.33 
                 13.5 
               
               
                 Stdev 
                 5.27 
                 9.94 
                 5.22 
                 9.75 
                 5.29 
                 9.70 
               
               
                 p (t-test) 
                   
                 0.014 
                   
                 0.0061 
                   
                 0.015 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 22.8 
                 38.9 
                 22.8 
                 38.9 
                 22.8 
                 38.9 
               
               
                 n (Patient) 
                 31 
                 50 
                 29 
                 52 
                 27 
                 54 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.48 
                 9.53 
                 8.56 
                 9.28 
                 10.8 
                 8.94 
               
               
                 Average 
                 12.3 
                 11.8 
                 12.9 
                 11.8 
                 14.3 
                 11.6 
               
               
                 Stdev 
                 8.63 
                 8.65 
                 8.87 
                 8.62 
                 8.41 
                 8.59 
               
               
                 p (t-test) 
                   
                 0.88 
                   
                 0.75 
                   
                 0.43 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 5.31 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 10 
                 61 
                 9 
                 62 
                 8 
                 64 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.62 
                 0.48 
                 0.69 
                 0.64 
                 0.46 
                 0.61 
                 0.62 
                 0.38 
               
               
                 SE 
                 0.10 
                 0.063 
                 0.098 
                 0.11 
                 0.062 
                 0.10 
                 0.13 
                 0.064 
                 0.098 
               
               
                 p Value 
                 0.40 
                 0.065 
                 0.83 
                 0.074 
                 0.020 
                 0.66 
                 0.40 
                 0.057 
                 0.22 
               
               
                 nCohort Recovered 
                 8 
                 31 
                 10 
                 5 
                 29 
                 9 
                 4 
                 27 
                 8 
               
               
                 nCohort Non-recovered 
                 74 
                 50 
                 61 
                 77 
                 52 
                 62 
                 78 
                 54 
                 64 
               
               
                 Cutoff Quartile 2 
                 6.18 
                 6.19 
                 6.19 
                 6.18 
                 6.19 
                 6.19 
                 6.18 
                 6.19 
                 6.19 
               
               
                 Sensitivity 
                 74% 
                 78% 
                 74% 
                 75% 
                 79% 
                 74% 
                  74% 
                 78% 
                 73% 
               
               
                 Specificity 
                 25% 
                 32% 
                 20% 
                 40% 
                 34% 
                 22% 
                  25% 
                 33% 
                 12% 
               
               
                 Cutoff Quartile 3 
                 9.66 
                 9.75 
                 9.00 
                 9.66 
                 9.75 
                 9.00 
                 9.66 
                 9.75 
                 8.94 
               
               
                 Sensitivity 
                 51% 
                 58% 
                 51% 
                 52% 
                 60% 
                 50% 
                  51% 
                 57% 
                 50% 
               
               
                 Specificity 
                 62% 
                 65% 
                 60% 
                 80% 
                 69% 
                 56% 
                  75% 
                 67% 
                 50% 
               
               
                 Cutoff Quartile 4 
                 15.6 
                 15.9 
                 14.3 
                 15.6 
                 15.9 
                 14.6 
                 15.6 
                 15.9 
                 14.6 
               
               
                 Sensitivity 
                 27% 
                 32% 
                 25% 
                 27% 
                 31% 
                 24% 
                  27% 
                 30% 
                 23% 
               
               
                 Specificity 
                 88% 
                 87% 
                 70% 
                 100% 
                 86% 
                 67% 
                 100% 
                 85% 
                 62% 
               
               
                 OR Quartile 2 
                 0.965 
                 1.69 
                 0.703 
                 2.04 
                 1.96 
                 0.821 
                 0.967 
                 1.75 
                 0.395 
               
               
                 p Value 
                 0.97 
                 0.31 
                 0.68 
                 0.45 
                 0.19 
                 0.82 
                 0.98 
                 0.28 
                 0.40 
               
               
                 Lower limit of 95% CI 
                 0.179 
                 0.617 
                 0.135 
                 0.316 
                 0.711 
                 0.154 
                 0.0950 
                 0.628 
                 0.0452 
               
               
                 Upper limit of 95% CI 
                 5.19 
                 4.62 
                 3.67 
                 13.1 
                 5.41 
                 4.37 
                 9.83 
                 4.88 
                 3.45 
               
               
                 OR Quartile 3 
                 1.76 
                 2.51 
                 1.55 
                 4.32 
                 3.28 
                 1.25 
                 3.16 
                 2.70 
                 1.00 
               
               
                 p Value 
                 0.46 
                 0.051 
                 0.53 
                 0.20 
                 0.016 
                 0.76 
                 0.33 
                 0.044 
                 1.0 
               
               
                 Lower limit of 95% CI 
                 0.392 
                 0.995 
                 0.397 
                 0.462 
                 1.25 
                 0.306 
                 0.315 
                 1.03 
                 0.230 
               
               
                 Upper limit of 95% CI 
                 7.90 
                 6.34 
                 6.05 
                 40.5 
                 8.59 
                 5.10 
                 31.7 
                 7.08 
                 4.35 
               
               
                 OR Quartile 4 
                 2.59 
                 3.18 
                 0.761 
                 4.19 
                 2.78 
                 0.638 
                 3.37 
                 2.42 
                 0.510 
               
               
                 p Value 
                 0.39 
                 0.060 
                 0.72 
                 0.34 
                 0.098 
                 0.56 
                 0.42 
                 0.15 
                 0.39 
               
               
                 Lower limit of 95% CI 
                 0.300 
                 0.950 
                 0.174 
                 0.222 
                 0.829 
                 0.142 
                 0.174 
                 0.721 
                 0.109 
               
               
                 Upper limit of 95% CI 
                 22.4 
                 10.6 
                 3.32 
                 79.0 
                 9.30 
                 2.87 
                 65.2 
                 8.13 
                 2.39 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 6.35 
                 10.2 
                 5.75 
                 10.2 
                 7.30 
                 9.96 
               
               
                 Average 
                 9.04 
                 12.5 
                 8.67 
                 12.5 
                 10.7 
                 12.2 
               
               
                 Stdev 
                 7.82 
                 8.84 
                 8.47 
                 8.74 
                 8.89 
                 8.77 
               
               
                 p (t-test) 
                   
                 0.24 
                   
                 0.29 
                   
                 0.72 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 5.31 
                 1.32 
               
               
                 Max 
                 30.3 
                 38.9 
                 30.3 
                 38.9 
                 30.3 
                 38.9 
               
               
                 n (Patient) 
                 10 
                 70 
                 8 
                 72 
                 6 
                 74 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.72 
                 10.9 
                 7.38 
                 10.9 
                 7.64 
                 10.7 
               
               
                 Average 
                 9.80 
                 13.7 
                 9.71 
                 13.6 
                 9.92 
                 13.4 
               
               
                 Stdev 
                 6.40 
                 9.78 
                 6.54 
                 9.62 
                 6.56 
                 9.62 
               
               
                 p (t-test) 
                   
                 0.037 
                   
                 0.038 
                   
                 0.064 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.3 
                 38.9 
                 30.3 
                 38.9 
                 30.3 
                 38.9 
               
               
                 n (Patient) 
                 31 
                 48 
                 29 
                 50 
                 28 
                 51 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.94 
                 9.74 
                 8.17 
                 9.91 
                 8.41 
                 9.56 
               
               
                 Average 
                 10.2 
                 12.4 
                 10.4 
                 12.4 
                 11.1 
                 12.1 
               
               
                 Stdev 
                 7.79 
                 8.93 
                 8.00 
                 8.89 
                 7.91 
                 8.87 
               
               
                 p (t-test) 
                   
                 0.36 
                   
                 0.44 
                   
                 0.69 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 3.20 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 15 
                 54 
                 14 
                 55 
                 13 
                 57 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.65 
                 0.62 
                 0.59 
                 0.69 
                 0.63 
                 0.58 
                 0.59 
                 0.61 
                 0.53 
               
               
                 SE 
                 0.085 
                 0.063 
                 0.081 
                 0.088 
                 0.063 
                 0.083 
                 0.11 
                 0.065 
                 0.088 
               
               
                 p Value 
                 0.076 
                 0.053 
                 0.28 
                 0.031 
                 0.038 
                 0.36 
                 0.42 
                 0.082 
                 0.72 
               
               
                 nCohort Recovered 
                 10 
                 31 
                 15 
                 8 
                 29 
                 14 
                 6 
                 28 
                 13 
               
               
                 nCohort Non-recovered 
                 70 
                 48 
                 54 
                 72 
                 50 
                 55 
                 74 
                 51 
                 57 
               
               
                 Cutoff Quartile 2 
                 6.16 
                 6.19 
                 6.18 
                 6.16 
                 6.19 
                 6.18 
                 6.16 
                 6.19 
                 6.19 
               
               
                 Sensitivity 
                 77% 
                 79% 
                 76% 
                 78% 
                 80% 
                 76% 
                 76% 
                 78% 
                 75% 
               
               
                 Specificity 
                 40% 
                 32% 
                 33% 
                 50% 
                 34% 
                 36% 
                 33% 
                 32% 
                 31% 
               
               
                 Cutoff Quartile 3 
                 9.28 
                 9.56 
                 9.00 
                 9.28 
                 9.56 
                 9.00 
                 9.28 
                 9.56 
                 8.94 
               
               
                 Sensitivity 
                 54% 
                 58% 
                 54% 
                 54% 
                 58% 
                 53% 
                 53% 
                 57% 
                 53% 
               
               
                 Specificity 
                 80% 
                 65% 
                 67% 
                 88% 
                 66% 
                 64% 
                 83% 
                 64% 
                 62% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 16.1 
                 14.5 
                 16.0 
                 16.1 
                 14.7 
                 16.0 
                 16.1 
                 14.7 
               
               
                 Sensitivity 
                 27% 
                 31% 
                 26% 
                 26% 
                 30% 
                 25% 
                 26% 
                 29% 
                 26% 
               
               
                 Specificity 
                 90% 
                 84% 
                 80% 
                 88% 
                 83% 
                 79% 
                 83% 
                 82% 
                 77% 
               
               
                 OR Quartile 2 
                 2.25 
                 1.81 
                 1.58 
                 3.50 
                 2.11 
                 1.79 
                 1.56 
                 1.72 
                 1.37 
               
               
                 p Value 
                 0.25 
                 0.26 
                 0.47 
                 0.10 
                 0.16 
                 0.36 
                 0.63 
                 0.30 
                 0.64 
               
               
                 Lower limit of 95% CI 
                 0.565 
                 0.649 
                 0.456 
                 0.786 
                 0.750 
                 0.510 
                 0.263 
                 0.611 
                 0.363 
               
               
                 Upper limit of 95% CI 
                 8.97 
                 5.05 
                 5.46 
                 15.6 
                 5.91 
                 6.31 
                 9.21 
                 4.86 
                 5.13 
               
               
                 OR Quartile 3 
                 4.75 
                 2.55 
                 2.32 
                 8.27 
                 2.62 
                 2.01 
                 5.57 
                 2.37 
                 1.78 
               
               
                 p Value 
                 0.059 
                 0.050 
                 0.17 
                 0.054 
                 0.046 
                 0.26 
                 0.13 
                 0.075 
                 0.36 
               
               
                 Lower limit of 95% CI 
                 0.941 
                 1.00 
                 0.699 
                 0.968 
                 1.02 
                 0.596 
                 0.620 
                 0.917 
                 0.518 
               
               
                 Upper limit of 95% CI 
                 24.0 
                 6.47 
                 7.70 
                 70.7 
                 6.78 
                 6.76 
                 50.0 
                 6.14 
                 6.10 
               
               
                 OR Quartile 4 
                 3.35 
                 2.36 
                 1.40 
                 2.51 
                 2.06 
                 1.25 
                 1.73 
                 1.92 
                 1.19 
               
               
                 p Value 
                 0.27 
                 0.14 
                 0.64 
                 0.40 
                 0.21 
                 0.76 
                 0.63 
                 0.26 
                 0.81 
               
               
                 Lower limit of 95% CI 
                 0.398 
                 0.760 
                 0.344 
                 0.289 
                 0.659 
                 0.305 
                 0.190 
                 0.613 
                 0.288 
               
               
                 Upper limit of 95% CI 
                 28.3 
                 7.35 
                 5.70 
                 21.8 
                 6.42 
                 5.15 
                 15.7 
                 5.99 
                 4.92 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.11 
                 10.6 
                 8.15 
                 10.3 
                 8.15 
                 10.3 
               
               
                 Average 
                 9.28 
                 13.1 
                 10.1 
                 12.7 
                 10.1 
                 12.7 
               
               
                 Stdev 
                 6.82 
                 8.98 
                 6.94 
                 8.98 
                 6.94 
                 8.98 
               
               
                 p (t-test) 
                   
                 0.055 
                   
                 0.23 
                   
                 0.23 
               
               
                 Min 
                 1.62 
                 1.32 
                 3.20 
                 1.32 
                 3.20 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 21 
                 56 
                 18 
                 59 
                 18 
                 59 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.25 
                 11.5 
                 7.38 
                 11.0 
                 7.38 
                 11.0 
               
               
                 Average 
                 8.89 
                 14.0 
                 9.06 
                 13.7 
                 9.06 
                 13.7 
               
               
                 Stdev 
                 5.17 
                 9.57 
                 5.16 
                 9.58 
                 5.16 
                 9.58 
               
               
                 p (t-test) 
                   
                 0.0046 
                   
                 0.0085 
                   
                 0.0085 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 22.8 
                 38.9 
                 22.8 
                 38.9 
                 22.8 
                 38.9 
               
               
                 n (Patient) 
                 32 
                 44 
                 31 
                 45 
                 31 
                 45 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.41 
                 10.0 
                 9.39 
                 9.74 
                 9.39 
                 9.74 
               
               
                 Average 
                 11.6 
                 13.0 
                 12.4 
                 12.4 
                 12.4 
                 12.4 
               
               
                 Stdev 
                 7.66 
                 9.86 
                 7.63 
                 9.71 
                 7.63 
                 9.71 
               
               
                 p (t-test) 
                   
                 0.57 
                   
                 0.99 
                   
                 0.99 
               
               
                 Min 
                 1.62 
                 1.32 
                 3.20 
                 1.32 
                 3.20 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 20 
                 37 
                 18 
                 40 
                 18 
                 40 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.65 
                 0.67 
                 0.52 
                 0.59 
                 0.65 
                 0.47 
                 0.59 
                 0.65 
                 0.47 
               
               
                 SE 
                 0.067 
                 0.062 
                 0.080 
                 0.074 
                 0.063 
                 0.082 
                 0.074 
                 0.063 
                 0.082 
               
               
                 p Value 
                 0.023 
                 0.0061 
                 0.78 
                 0.21 
                 0.017 
                 0.73 
                 0.21 
                 0.017 
                 0.73 
               
               
                 nCohort Recovered 
                 21 
                 32 
                 20 
                 18 
                 31 
                 18 
                 18 
                 31 
                 18 
               
               
                 nCohort Non-recovered 
                 56 
                 44 
                 37 
                 59 
                 45 
                 40 
                 59 
                 45 
                 40 
               
               
                 Cutoff Quartile 2 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.29 
                 6.19 
                 6.19 
                 6.29 
               
               
                 Sensitivity 
                 80% 
                 82% 
                 76% 
                 78% 
                 80% 
                 75% 
                 78% 
                 80% 
                 75% 
               
               
                 Specificity 
                 43% 
                 34% 
                 30% 
                 39% 
                 32% 
                 28% 
                 39% 
                 32% 
                 28% 
               
               
                 Cutoff Quartile 3 
                 9.56 
                 9.28 
                 9.91 
                 9.56 
                 9.28 
                 9.74 
                 9.56 
                 9.28 
                 9.74 
               
               
                 Sensitivity 
                 57% 
                 61% 
                 51% 
                 54% 
                 60% 
                 50% 
                 54% 
                 60% 
                 50% 
               
               
                 Specificity 
                 71% 
                 66% 
                 55% 
                 67% 
                 65% 
                 50% 
                 67% 
                 65% 
                 50% 
               
               
                 Cutoff Quartile 4 
                 15.9 
                 15.0 
                 15.9 
                 15.9 
                 15.0 
                 15.6 
                 15.9 
                 15.0 
                 15.6 
               
               
                 Sensitivity 
                 29% 
                 34% 
                 24% 
                 27% 
                 33% 
                 25% 
                 27% 
                 33% 
                 25% 
               
               
                 Specificity 
                 86% 
                 88% 
                 75% 
                 83% 
                 87% 
                 72% 
                 83% 
                 87% 
                 72% 
               
               
                 OR Quartile 2 
                 3.07 
                 2.36 
                 1.33 
                 2.25 
                 1.90 
                 1.15 
                 2.25 
                 1.90 
                 1.15 
               
               
                 p Value 
                 0.043 
                 0.11 
                 0.64 
                 0.16 
                 0.23 
                 0.82 
                 0.16 
                 0.23 
                 0.82 
               
               
                 Lower limit of 95% CI 
                 1.03 
                 0.818 
                 0.395 
                 0.727 
                 0.667 
                 0.329 
                 0.727 
                 0.667 
                 0.329 
               
               
                 Upper limit of 95% CI 
                 9.10 
                 6.79 
                 4.50 
                 6.97 
                 5.44 
                 4.05 
                 6.97 
                 5.44 
                 4.05 
               
               
                 OR Quartile 3 
                 3.33 
                 3.03 
                 1.29 
                 2.37 
                 2.73 
                 1.00 
                 2.37 
                 2.73 
                 1.00 
               
               
                 p Value 
                 0.030 
                 0.022 
                 0.65 
                 0.13 
                 0.038 
                 1.0 
                 0.13 
                 0.038 
                 1.0 
               
               
                 Lower limit of 95% CI 
                 1.13 
                 1.17 
                 0.433 
                 0.784 
                 1.06 
                 0.329 
                 0.784 
                 1.06 
                 0.329 
               
               
                 Upper limit of 95% CI 
                 9.86 
                 7.83 
                 3.84 
                 7.16 
                 7.03 
                 3.04 
                 7.16 
                 7.03 
                 3.04 
               
               
                 OR Quartile 4 
                 2.40 
                 3.62 
                 0.964 
                 1.86 
                 3.38 
                 0.867 
                 1.86 
                 3.38 
                 0.867 
               
               
                 p Value 
                 0.20 
                 0.039 
                 0.95 
                 0.37 
                 0.051 
                 0.82 
                 0.37 
                 0.051 
                 0.82 
               
               
                 Lower limit of 95% CI 
                 0.620 
                 1.07 
                 0.273 
                 0.475 
                 0.997 
                 0.247 
                 0.475 
                 0.997 
                 0.247 
               
               
                 Upper limit of 95% CI 
                 9.28 
                 12.3 
                 3.40 
                 7.29 
                 11.4 
                 3.04 
                 7.29 
                 11.4 
                 3.04 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in EDTA samples for the “recovered” and “non-recovered” cohorts where recovery starts 
               
               
                 at 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.17 
                 10.6 
                 8.17 
                 10.6 
                 8.17 
                 10.6 
               
               
                 Average 
                 9.65 
                 12.8 
                 9.65 
                 12.8 
                 9.65 
                 12.8 
               
               
                 Stdev 
                 5.94 
                 9.17 
                 5.94 
                 9.17 
                 5.94 
                 9.17 
               
               
                 p (t-test) 
                   
                 0.094 
                   
                 0.094 
                   
                 0.094 
               
               
                 Min 
                 3.20 
                 1.32 
                 3.20 
                 1.32 
                 3.20 
                 1.32 
               
               
                 Max 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
               
               
                 n (Patient) 
                 22 
                 52 
                 22 
                 52 
                 22 
                 52 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.90 
                 10.9 
                 7.90 
                 10.9 
                 7.94 
                 10.6 
               
               
                 Average 
                 10.4 
                 12.7 
                 9.67 
                 13.1 
                 9.84 
                 12.9 
               
               
                 Stdev 
                 8.00 
                 8.57 
                 6.69 
                 9.18 
                 6.88 
                 9.05 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.071 
                   
                 0.12 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 36.8 
                 38.9 
                 34.6 
                 38.9 
                 34.6 
                 38.9 
               
               
                 n (Patient) 
                 33 
                 40 
                 31 
                 42 
                 29 
                 44 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 10.2 
                 9.46 
                 10.2 
                 9.46 
                 10.2 
                 9.46 
               
               
                 Average 
                 11.9 
                 12.8 
                 11.9 
                 12.8 
                 11.9 
                 12.8 
               
               
                 Stdev 
                 5.52 
                 10.2 
                 5.52 
                 10.2 
                 5.52 
                 10.2 
               
               
                 p (t-test) 
                   
                 0.69 
                   
                 0.69 
                   
                 0.69 
               
               
                 Min 
                 5.31 
                 1.32 
                 5.31 
                 1.32 
                 5.31 
                 1.32 
               
               
                 Max 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
               
               
                 n (Patient) 
                 14 
                 34 
                 14 
                 34 
                 14 
                 34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.60 
                 0.60 
                 0.45 
                 0.60 
                 0.63 
                 0.45 
                 0.60 
                 0.61 
                 0.45 
               
               
                 SE 
                 0.070 
                 0.066 
                 0.091 
                 0.070 
                 0.065 
                 0.091 
                 0.070 
                 0.066 
                 0.091 
               
               
                 p Value 
                 0.16 
                 0.12 
                 0.58 
                 0.16 
                 0.055 
                 0.58 
                 0.16 
                 0.10 
                 0.58 
               
               
                 nCohort Recovered 
                 22 
                 33 
                 14 
                 22 
                 31 
                 14 
                 22 
                 29 
                 14 
               
               
                 nCohort Non-recovered 
                 52 
                 40 
                 34 
                 52 
                 42 
                 34 
                 52 
                 44 
                 34 
               
               
                 Cutoff Quartile 2 
                 6.19 
                 6.18 
                 6.96 
                 6.19 
                 6.18 
                 6.96 
                 6.19 
                 6.18 
                 6.96 
               
               
                 Sensitivity 
                 79% 
                 78% 
                 71% 
                 79% 
                 79% 
                 71% 
                 79% 
                 80% 
                 71% 
               
               
                 Specificity 
                 36% 
                 30% 
                 14% 
                 36% 
                 32% 
                 14% 
                 36% 
                 34% 
                 14% 
               
               
                 Cutoff Quartile 3 
                 9.28 
                 9.00 
                 9.96 
                 9.28 
                 9.00 
                 9.96 
                 9.28 
                 9.00 
                 9.96 
               
               
                 Sensitivity 
                 56% 
                 60% 
                 47% 
                 56% 
                 60% 
                 47% 
                 56% 
                 57% 
                 47% 
               
               
                 Specificity 
                 64% 
                 64% 
                 43% 
                 64% 
                 65% 
                 43% 
                 64% 
                 62% 
                 43% 
               
               
                 Cutoff Quartile 4 
                 14.7 
                 14.6 
                 14.9 
                 14.7 
                 14.6 
                 14.9 
                 14.7 
                 14.6 
                 14.9 
               
               
                 Sensitivity 
                 31% 
                 32% 
                 26% 
                 31% 
                 33% 
                 26% 
                 31% 
                 32% 
                 26% 
               
               
                 Specificity 
                 86% 
                 85% 
                 79% 
                 86% 
                 87% 
                 79% 
                 86% 
                 86% 
                 79% 
               
               
                 OR Quartile 2 
                 2.13 
                 1.50 
                 0.400 
                 2.13 
                 1.75 
                 0.400 
                 2.13 
                 2.05 
                 0.400 
               
               
                 p Value 
                 0.18 
                 0.45 
                 0.28 
                 0.18 
                 0.30 
                 0.28 
                 0.18 
                 0.19 
                 0.28 
               
               
                 Lower limit of 95% CI 
                 0.713 
                 0.524 
                 0.0754 
                 0.713 
                 0.609 
                 0.0754 
                 0.713 
                 0.709 
                 0.0754 
               
               
                 Upper limit of 95% CI 
                 6.36 
                 4.28 
                 2.12 
                 6.36 
                 5.01 
                 2.12 
                 6.36 
                 5.91 
                 2.12 
               
               
                 OR Quartile 3 
                 2.21 
                 2.62 
                 0.667 
                 2.21 
                 2.67 
                 0.667 
                 2.21 
                 2.15 
                 0.667 
               
               
                 p Value 
                 0.13 
                 0.047 
                 0.53 
                 0.13 
                 0.045 
                 0.53 
                 0.13 
                 0.12 
                 0.53 
               
               
                 Lower limit of 95% CI 
                 0.790 
                 1.01 
                 0.190 
                 0.790 
                 1.02 
                 0.190 
                 0.790 
                 0.826 
                 0.190 
               
               
                 Upper limit of 95% CI 
                 6.16 
                 6.79 
                 2.34 
                 6.16 
                 6.98 
                 2.34 
                 6.16 
                 5.61 
                 2.34 
               
               
                 OR Quartile 4 
                 2.81 
                 2.70 
                 1.32 
                 2.81 
                 3.38 
                 1.32 
                 2.81 
                 2.92 
                 1.32 
               
               
                 p Value 
                 0.13 
                 0.093 
                 0.71 
                 0.13 
                 0.053 
                 0.71 
                 0.13 
                 0.088 
                 0.71 
               
               
                 Lower limit of 95% CI 
                 0.728 
                 0.846 
                 0.298 
                 0.728 
                 0.986 
                 0.298 
                 0.728 
                 0.851 
                 0.298 
               
               
                 Upper limit of 95% CI 
                 10.9 
                 8.59 
                 5.84 
                 10.9 
                 11.6 
                 5.84 
                 10.9 
                 9.99 
                 5.84 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “recovered” and “non-recovered” cohorts where 
               
               
                 recovery starts within 7 days after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE citeria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.06 
                 10.2 
                 8.48 
                 10.5 
                 8.48 
                 10.5 
               
               
                 Average 
                 11.3 
                 12.9 
                 11.1 
                 13.0 
                 11.2 
                 12.8 
               
               
                 Stdev 
                 7.16 
                 9.92 
                 7.39 
                 9.52 
                 7.40 
                 9.46 
               
               
                 p (t-test) 
                   
                 0.41 
                   
                 0.32 
                   
                 0.42 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 3.20 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 22 
                 52 
                 22 
                 52 
                 22 
                 52 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.48 
                 10.4 
                 8.41 
                 10.5 
                 8.41 
                 10.5 
               
               
                 Average 
                 11.6 
                 12.9 
                 11.4 
                 13.1 
                 11.4 
                 12.9 
               
               
                 Stdev 
                 7.97 
                 9.65 
                 8.08 
                 9.40 
                 8.39 
                 8.99 
               
               
                 p (t-test) 
                   
                 0.54 
                   
                 0.41 
                   
                 0.46 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 36.8 
                 38.9 
                 36.8 
                 38.9 
                 36.8 
                 38.9 
               
               
                 n (Patient) 
                 48 
                 33 
                 46 
                 35 
                 42 
                 39 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.48 
                 10.2 
                 8.41 
                 10.4 
                 8.48 
                 10.2 
               
               
                 Average 
                 11.1 
                 13.1 
                 10.4 
                 13.2 
                 10.7 
                 13.0 
               
               
                 Stdev 
                 7.72 
                 9.28 
                 6.57 
                 9.30 
                 6.48 
                 9.36 
               
               
                 p (t-test) 
                   
                 0.33 
                   
                 0.12 
                   
                 0.21 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 3.20 
                 1.32 
               
               
                 Max 
                 33.3 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 30 
                 48 
                 31 
                 47 
                 30 
                 48 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.53 
                 0.53 
                 0.55 
                 0.56 
                 0.55 
                 0.58 
                 0.54 
                 0.56 
                 0.55 
               
               
                 SE 
                 0.063 
                 0.066 
                 0.067 
                 0.063 
                 0.065 
                 0.066 
                 0.063 
                 0.064 
                 0.067 
               
               
                 p Value 
                 0.69 
                 0.65 
                 0.44 
                 0.38 
                 0.40 
                 0.24 
                 0.49 
                 0.31 
                 0.43 
               
               
                 nCohort Recovered 
                 44 
                 48 
                 30 
                 40 
                 46 
                 31 
                 38 
                 42 
                 30 
               
               
                 nCohort Non-recovered 
                 40 
                 33 
                 48 
                 44 
                 35 
                 47 
                 46 
                 39 
                 48 
               
               
                 Cutoff Quartile 2 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
               
               
                 Sensitivity 
                 75% 
                 76% 
                 75% 
                 77% 
                 77% 
                 77% 
                 76% 
                 79% 
                 75% 
               
               
                 Specificity 
                 25% 
                 27% 
                 30% 
                 28% 
                 28% 
                 32% 
                 26% 
                 31% 
                 30% 
               
               
                 Cutoff Quartile 3 
                 9.66 
                 9.75 
                 9.66 
                 9.66 
                 9.75 
                 9.66 
                 9.66 
                 9.75 
                 9.66 
               
               
                 Sensitivity 
                 52% 
                 55% 
                 54% 
                 55% 
                 57% 
                 55% 
                 54% 
                 56% 
                 54% 
               
               
                 Specificity 
                 52% 
                 54% 
                 57% 
                 55% 
                 57% 
                 58% 
                 55% 
                 57% 
                 57% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.6 
                 16.0 
                 15.9 
                 15.6 
                 16.0 
                 15.9 
                 15.6 
               
               
                 Sensitivity 
                 30% 
                 30% 
                 31% 
                 30% 
                 31% 
                 32% 
                 28% 
                 28% 
                 31% 
               
               
                 Specificity 
                 80% 
                 79% 
                 83% 
                 80% 
                 80% 
                 84% 
                 79% 
                 79% 
                 83% 
               
               
                 OR Quartile 2 
                 1.00 
                 1.16 
                 1.29 
                 1.29 
                 1.33 
                 1.56 
                 1.14 
                 1.74 
                 1.29 
               
               
                 p Value 
                 1.0 
                 0.77 
                 0.63 
                 0.61 
                 0.58 
                 0.39 
                 0.80 
                 0.29 
                 0.63 
               
               
                 Lower limit of 95% CI 
                 0.372 
                 0.419 
                 0.464 
                 0.480 
                 0.481 
                 0.567 
                 0.422 
                 0.629 
                 0.464 
               
               
                 Upper limit of 95% CI 
                 2.69 
                 3.22 
                 3.56 
                 3.47 
                 3.68 
                 4.29 
                 3.06 
                 4.80 
                 3.56 
               
               
                 OR Quartile 3 
                 1.21 
                 1.42 
                 1.55 
                 1.47 
                 1.73 
                 1.71 
                 1.47 
                 1.73 
                 1.55 
               
               
                 p Value 
                 0.66 
                 0.44 
                 0.35 
                 0.38 
                 0.22 
                 0.25 
                 0.38 
                 0.22 
                 0.35 
               
               
                 Lower limit of 95% CI 
                 0.514 
                 0.582 
                 0.617 
                 0.620 
                 0.713 
                 0.686 
                 0.620 
                 0.716 
                 0.617 
               
               
                 Upper limit of 95% CI 
                 2.85 
                 3.45 
                 3.87 
                 3.47 
                 4.21 
                 4.29 
                 3.49 
                 4.16 
                 3.87 
               
               
                 OR Quartile 4 
                 1.67 
                 1.65 
                 2.27 
                 1.68 
                 1.88 
                 2.44 
                 1.48 
                 1.44 
                 2.27 
               
               
                 p Value 
                 0.32 
                 0.33 
                 0.16 
                 0.32 
                 0.22 
                 0.12 
                 0.45 
                 0.48 
                 0.16 
               
               
                 Lower limit of 95% CI 
                 0.615 
                 0.597 
                 0.728 
                 0.611 
                 0.680 
                 0.782 
                 0.538 
                 0.522 
                 0.728 
               
               
                 Upper limit of 95% CI 
                 4.52 
                 4.57 
                 7.09 
                 4.60 
                 5.22 
                 7.60 
                 4.06 
                 3.97 
                 7.09 
               
               
                   
               
            
           
         
       
     
     Example 9. Use of C-C Motif Chemokine 16 for Evaluating Renal Status in Patients Admitted to the ICU: Recovery to RIFLE 0 and R from RIFLE I and F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 16 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output during a period starting at 12, 24, 48, or 72 hours after sample collection or at any time within 7 days after sample collection. Two cohorts are defined to represent a “recovered” and a “non-recovered” population. “Recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0) or risk of injury (R). “Non-recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is injury (I) or failure (F). If a patient dies or is placed on renal replacement therapy (RRT) within 9 days of enrollment, the patient is considered “non-recovered”. 
     The ability to distinguish the “recovered” and “non-recovered” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 9.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.00734 
                 0.0207 
                 0.00738 
                 0.0206 
                 0.00908 
                 0.0194 
               
               
                 Average 
                 0.0126 
                 0.0844 
                 0.0129 
                 0.0832 
                 0.0134 
                 0.0819 
               
               
                 Stdev 
                 0.0148 
                 0.375 
                 0.0151 
                 0.372 
                 0.0154 
                 0.369 
               
               
                 p (t-test) 
                   
                 0.14 
                   
                 0.14 
                   
                 0.15 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.0518 
                 2.98 
                 0.0518 
                 2.98 
                 0.0518 
                 2.98 
               
               
                 n (Patient) 
                 19 
                 62 
                 18 
                 63 
                 17 
                 64 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0108 
                 0.0262 
                 0.0142 
                 0.0217 
                 0.0142 
                 0.0217 
               
               
                 Average 
                 0.0190 
                 0.135 
                 0.0197 
                 0.127 
                 0.0197 
                 0.127 
               
               
                 Stdev 
                 0.0228 
                 0.500 
                 0.0230 
                 0.487 
                 0.0230 
                 0.487 
               
               
                 p (t-test) 
                   
                 0.19 
                   
                 0.20 
                   
                 0.20 
               
               
                 Min 
                 4.13E−6 
                 6.68E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 47 
                 34 
                 45 
                 36 
                 45 
                 36 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0125 
                 0.0217 
                 0.0108 
                 0.0225 
                 0.0125 
                 0.0208 
               
               
                 Average 
                 0.0293 
                 0.0914 
                 0.0282 
                 0.0932 
                 0.0290 
                 0.0899 
               
               
                 Stdev 
                 0.0407 
                 0.408 
                 0.0400 
                 0.412 
                 0.0409 
                 0.405 
               
               
                 p (t-test) 
                   
                 0.29 
                   
                 0.28 
                   
                 0.29 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 20 
                 52 
                 21 
                 51 
                 20 
                 53 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.67 
                 0.68 
                 0.55 
                 0.67 
                 0.64 
                 0.57 
                 0.66 
                 0.64 
                 0.56 
               
               
                 SE 
                 0.066 
                 0.061 
                 0.075 
                 0.068 
                 0.062 
                 0.073 
                 0.069 
                 0.062 
                 0.074 
               
               
                 p Value 
                 0.0095 
                 0.0039 
                 0.48 
                 0.014 
                 0.023 
                 0.37 
                 0.021 
                 0.023 
                 0.40 
               
               
                 nCohort Recovered 
                 19 
                 47 
                 20 
                 18 
                 45 
                 21 
                 17 
                 45 
                 20 
               
               
                 nCohort Non-recovered 
                 62 
                 34 
                 52 
                 63 
                 36 
                 51 
                 64 
                 36 
                 53 
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00161 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 Sensitivity 
                 73% 
                 82% 
                 73% 
                 73% 
                 81% 
                 73% 
                 73% 
                 81% 
                 74% 
               
               
                 Specificity 
                 32% 
                 36% 
                 20% 
                 33% 
                 36% 
                 24% 
                 35% 
                 36% 
                 30% 
               
               
                 Cutoff Quartile 3 
                 0.0157 
                 0.0157 
                 0.0193 
                 0.0157 
                 0.0157 
                 0.0193 
                 0.0157 
                 0.0157 
                 0.0181 
               
               
                 Sensitivity 
                 56% 
                 62% 
                 54% 
                 56% 
                 58% 
                 55% 
                 55% 
                 58% 
                 53% 
               
               
                 Specificity 
                 74% 
                 60% 
                 60% 
                 72% 
                 58% 
                 62% 
                 71% 
                 58% 
                 60% 
               
               
                 Cutoff Quartile 4 
                 0.0427 
                 0.0427 
                 0.0464 
                 0.0427 
                 0.0427 
                 0.0464 
                 0.0427 
                 0.0427 
                 0.0460 
               
               
                 Sensitivity 
                 31% 
                 38% 
                 27% 
                 30% 
                 36% 
                 27% 
                 30% 
                 36% 
                 26% 
               
               
                 Specificity 
                 95% 
                 85% 
                 80% 
                 94% 
                 84% 
                 81% 
                 94% 
                 84% 
                 80% 
               
               
                 OR Quartile 2 
                 1.22 
                 2.64 
                 0.679 
                 1.35 
                 2.29 
                 0.826 
                 1.51 
                 2.29 
                 1.19 
               
               
                 p Value 
                 0.73 
                 0.073 
                 0.54 
                 0.60 
                 0.11 
                 0.75 
                 0.48 
                 0.11 
                 0.76 
               
               
                 Lower limit of 95% CI 
                 0.400 
                 0.913 
                 0.193 
                 0.438 
                 0.819 
                 0.254 
                 0.483 
                 0.819 
                 0.384 
               
               
                 Upper limit of 95% CI 
                 3.73 
                 7.66 
                 2.38 
                 4.18 
                 6.38 
                 2.68 
                 4.71 
                 6.38 
                 3.71 
               
               
                 OR Quartile 3 
                 3.63 
                 2.38 
                 1.75 
                 3.25 
                 1.92 
                 1.98 
                 2.90 
                 1.92 
                 1.68 
               
               
                 p Value 
                 0.026 
                 0.060 
                 0.30 
                 0.044 
                 0.15 
                 0.20 
                 0.071 
                 0.15 
                 0.33 
               
               
                 Lower limit of 95% CI 
                 1.16 
                 0.964 
                 0.614 
                 1.03 
                 0.788 
                 0.700 
                 0.914 
                 0.788 
                 0.591 
               
               
                 Upper limit of 95% CI 
                 11.3 
                 5.88 
                 4.99 
                 10.2 
                 4.66 
                 5.59 
                 9.18 
                 4.66 
                 4.78 
               
               
                 OR Quartile 4 
                 7.95 
                 3.54 
                 1.47 
                 7.34 
                 3.07 
                 1.61 
                 6.76 
                 3.07 
                 1.44 
               
               
                 p Value 
                 0.051 
                 0.019 
                 0.54 
                 0.061 
                 0.037 
                 0.46 
                 0.073 
                 0.037 
                 0.57 
               
               
                 Lower limit of 95% CI 
                 0.989 
                 1.23 
                 0.420 
                 0.910 
                 1.07 
                 0.460 
                 0.835 
                 1.07 
                 0.410 
               
               
                 Upper limit of 95% CI 
                 64.0 
                 10.2 
                 5.17 
                 59.2 
                 8.81 
                 5.62 
                 54.6 
                 8.81 
                 5.03 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0125 
                 0.0217 
                 0.0142 
                 0.0208 
                 0.0146 
                 0.0195 
               
               
                 Average 
                 0.0158 
                 0.0909 
                 0.0162 
                 0.0895 
                 0.0167 
                 0.0880 
               
               
                 Stdev 
                 0.0150 
                 0.394 
                 0.0152 
                 0.390 
                 0.0154 
                 0.387 
               
               
                 p (t-test) 
                   
                 0.16 
                   
                 0.17 
                   
                 0.17 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.0518 
                 2.98 
                 0.0518 
                 2.98 
                 0.0518 
                 2.98 
               
               
                 n (Patient) 
                 24 
                 56 
                 23 
                 57 
                 22 
                 58 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0142 
                 0.0225 
                 0.0146 
                 0.0217 
                 0.0142 
                 0.0225 
               
               
                 Average 
                 0.0199 
                 0.131 
                 0.0202 
                 0.127 
                 0.0197 
                 0.125 
               
               
                 Stdev 
                 0.0229 
                 0.493 
                 0.0231 
                 0.487 
                 0.0231 
                 0.480 
               
               
                 p (t-test) 
                   
                 0.20 
                   
                 0.20 
                   
                 0.20 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
                 0.106 
                 2.98 
               
               
                 n (Patient) 
                 45 
                 35 
                 44 
                 36 
                 43 
                 37 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0167 
                 0.0237 
                 0.0153 
                 0.0249 
                 0.0167 
                 0.0225 
               
               
                 Average 
                 0.0298 
                 0.100 
                 0.0288 
                 0.103 
                 0.0296 
                 0.0985 
               
               
                 Stdev 
                 0.0382 
                 0.433 
                 0.0376 
                 0.438 
                 0.0384 
                 0.429 
               
               
                 p (t-test) 
                   
                 0.28 
                   
                 0.27 
                   
                 0.29 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 22 
                 46 
                 23 
                 45 
                 22 
                 47 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.61 
                 0.65 
                 0.52 
                 0.61 
                 0.64 
                 0.54 
                 0.60 
                 0.65 
                 0.53 
               
               
                 SE 
                 0.066 
                 0.063 
                 0.075 
                 0.068 
                 0.063 
                 0.074 
                 0.069 
                 0.062 
                 0.074 
               
               
                 p Value 
                 0.086 
                 0.021 
                 0.76 
                 0.11 
                 0.030 
                 0.61 
                 0.16 
                 0.018 
                 0.69 
               
               
                 nCohort Recovered 
                 24 
                 45 
                 22 
                 23 
                 44 
                 23 
                 22 
                 43 
                 22 
               
               
                 nCohort Non-recovered 
                 56 
                 35 
                 46 
                 57 
                 36 
                 45 
                 58 
                 37 
                 47 
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00161 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 Sensitivity 
                 70% 
                 80% 
                 70% 
                 70% 
                 81% 
                 69% 
                 71% 
                 81% 
                 70% 
               
               
                 Specificity 
                 21% 
                 33% 
                 14% 
                 22% 
                 34% 
                 17% 
                 23% 
                 35% 
                 23% 
               
               
                 Cutoff Quartile 3 
                 0.0165 
                 0.0165 
                 0.0207 
                 0.0165 
                 0.0165 
                 0.0207 
                 0.0165 
                 0.0165 
                 0.0206 
               
               
                 Sensitivity 
                 55% 
                 60% 
                 54% 
                 54% 
                 58% 
                 56% 
                 53% 
                 59% 
                 53% 
               
               
                 Specificity 
                 62% 
                 58% 
                 59% 
                 61% 
                 57% 
                 61% 
                 59% 
                 58% 
                 59% 
               
               
                 Cutoff Quartile 4 
                 0.0435 
                 0.0435 
                 0.0464 
                 0.0435 
                 0.0435 
                 0.0464 
                 0.0435 
                 0.0435 
                 0.0460 
               
               
                 Sensitivity 
                 32% 
                 37% 
                 28% 
                 32% 
                 36% 
                 29% 
                 31% 
                 35% 
                 28% 
               
               
                 Specificity 
                 92% 
                 84% 
                 82% 
                 91% 
                 84% 
                 83% 
                 91% 
                 84% 
                 82% 
               
               
                 OR Quartile 2 
                 0.604 
                 2.00 
                 0.361 
                 0.654 
                 2.14 
                 0.466 
                 0.709 
                 2.30 
                 0.693 
               
               
                 p Value 
                 0.38 
                 0.19 
                 0.14 
                 0.47 
                 0.15 
                 0.23 
                 0.56 
                 0.12 
                 0.54 
               
               
                 Lower limit of 95% CI 
                 0.193 
                 0.711 
                 0.0917 
                 0.209 
                 0.762 
                 0.134 
                 0.225 
                 0.816 
                 0.214 
               
               
                 Upper limit of 95% CI 
                 1.88 
                 5.63 
                 1.42 
                 2.05 
                 6.03 
                 1.63 
                 2.23 
                 6.46 
                 2.25 
               
               
                 OR Quartile 3 
                 2.07 
                 2.05 
                 1.72 
                 1.85 
                 1.84 
                 1.94 
                 1.66 
                 2.04 
                 1.64 
               
               
                 p Value 
                 0.15 
                 0.12 
                 0.30 
                 0.22 
                 0.18 
                 0.20 
                 0.32 
                 0.12 
                 0.34 
               
               
                 Lower limit of 95% CI 
                 0.776 
                 0.836 
                 0.614 
                 0.692 
                 0.755 
                 0.699 
                 0.614 
                 0.834 
                 0.589 
               
               
                 Upper limit of 95% CI 
                 5.51 
                 5.04 
                 4.81 
                 4.97 
                 4.49 
                 5.41 
                 4.48 
                 4.98 
                 4.57 
               
               
                 OR Quartile 4 
                 5.21 
                 3.21 
                 1.77 
                 4.85 
                 2.99 
                 1.93 
                 4.50 
                 2.79 
                 1.72 
               
               
                 p Value 
                 0.037 
                 0.031 
                 0.37 
                 0.047 
                 0.042 
                 0.31 
                 0.058 
                 0.057 
                 0.40 
               
               
                 Lower limit of 95% CI 
                 1.10 
                 1.11 
                 0.503 
                 1.02 
                 1.04 
                 0.549 
                 0.949 
                 0.971 
                 0.489 
               
               
                 Upper limit of 95% CI 
                 24.6 
                 9.24 
                 6.25 
                 22.9 
                 8.59 
                 6.78 
                 21.3 
                 7.99 
                 6.05 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 48 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0129 
                 0.0262 
                 0.0152 
                 0.0195 
                 0.0153 
                 0.0182 
               
               
                 Average 
                 0.0232 
                 0.109 
                 0.0257 
                 0.0999 
                 0.0265 
                 0.0978 
               
               
                 Stdev 
                 0.0336 
                 0.452 
                 0.0347 
                 0.433 
                 0.0349 
                 0.429 
               
               
                 p (t-test) 
                   
                 0.23 
                   
                 0.26 
                   
                 0.27 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 24 
                 56 
                 23 
                 57 
                 22 
                 58 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0151 
                 0.0195 
                 0.0146 
                 0.0208 
                 0.0146 
                 0.0208 
               
               
                 Average 
                 0.0248 
                 0.132 
                 0.0244 
                 0.129 
                 0.0244 
                 0.129 
               
               
                 Stdev 
                 0.0321 
                 0.516 
                 0.0323 
                 0.508 
                 0.0323 
                 0.508 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.25 
                   
                 0.25 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 47 
                 32 
                 46 
                 33 
                 46 
                 33 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0157 
                 0.0315 
                 0.0206 
                 0.0208 
                 0.0227 
                 0.0190 
               
               
                 Average 
                 0.0295 
                 0.141 
                 0.0336 
                 0.121 
                 0.0350 
                 0.118 
               
               
                 Stdev 
                 0.0373 
                 0.532 
                 0.0386 
                 0.495 
                 0.0388 
                 0.488 
               
               
                 p (t-test) 
                   
                 0.27 
                   
                 0.31 
                   
                 0.33 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 29 
                 30 
                 25 
                 35 
                 24 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.61 
                 0.65 
                 0.52 
                 0.61 
                 0.64 
                 0.54 
                 0.60 
                 0.65 
                 0.53 
               
               
                 SE 
                 0.066 
                 0.063 
                 0.075 
                 0.068 
                 0.063 
                 0.074 
                 0.069 
                 0.062 
                 0.074 
               
               
                 p Value 
                 0.086 
                 0.021 
                 0.76 
                 0.11 
                 0.030 
                 0.61 
                 0.16 
                 0.018 
                 0.69 
               
               
                 nCohort Recovered 
                 24 
                 45 
                 22 
                 23 
                 44 
                 23 
                 22 
                 43 
                 22 
               
               
                 nCohort Non-recovered 
                 56 
                 35 
                 46 
                 57 
                 36 
                 45 
                 58 
                 37 
                 47 
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00161 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 Sensitivity 
                 70% 
                 80% 
                 70% 
                 70% 
                 81% 
                 69% 
                 71% 
                 81% 
                 70% 
               
               
                 Specificity 
                 21% 
                 33% 
                 14% 
                 22% 
                 34% 
                 17% 
                 23% 
                 35% 
                 23% 
               
               
                 Cutoff Quartile 3 
                 0.0165 
                 0.0165 
                 0.0207 
                 0.0165 
                 0.0165 
                 0.0207 
                 0.0165 
                 0.0165 
                 0.0206 
               
               
                 Sensitivity 
                 55% 
                 60% 
                 54% 
                 54% 
                 58% 
                 56% 
                 53% 
                 59% 
                 53% 
               
               
                 Specificity 
                 62% 
                 58% 
                 59% 
                 61% 
                 57% 
                 61% 
                 59% 
                 58% 
                 59% 
               
               
                 Cutoff Quartile 4 
                 0.0435 
                 0.0435 
                 0.0464 
                 0.0435 
                 0.0435 
                 0.0464 
                 0.0435 
                 0.0435 
                 0.0460 
               
               
                 Sensitivity 
                 32% 
                 37% 
                 28% 
                 32% 
                 36% 
                 29% 
                 31% 
                 35% 
                 28% 
               
               
                 Specificity 
                 92% 
                 84% 
                 82% 
                 91% 
                 84% 
                 83% 
                 91% 
                 84% 
                 82% 
               
               
                 OR Quartile 2 
                 0.604 
                 2.00 
                 0.361 
                 0.654 
                 2.14 
                 0.466 
                 0.709 
                 2.30 
                 0.693 
               
               
                 p Value 
                 0.38 
                 0.19 
                 0.14 
                 0.47 
                 0.15 
                 0.23 
                 0.56 
                 0.12 
                 0.54 
               
               
                 Lower limit of 95% CI 
                 0.193 
                 0.711 
                 0.0917 
                 0.209 
                 0.762 
                 0.134 
                 0.225 
                 0.816 
                 0.214 
               
               
                 Upper limit of 95% CI 
                 1.88 
                 5.63 
                 1.42 
                 2.05 
                 6.03 
                 1.63 
                 2.23 
                 6.46 
                 2.25 
               
               
                 OR Quartile 3 
                 2.07 
                 2.05 
                 1.72 
                 1.85 
                 1.84 
                 1.94 
                 1.66 
                 2.04 
                 1.64 
               
               
                 p Value 
                 0.15 
                 0.12 
                 0.30 
                 0.22 
                 0.18 
                 0.20 
                 0.32 
                 0.12 
                 0.34 
               
               
                 Lower limit of 95% CI 
                 0.776 
                 0.836 
                 0.614 
                 0.692 
                 0.755 
                 0.699 
                 0.614 
                 0.834 
                 0.589 
               
               
                 Upper limit of 95% CI 
                 5.51 
                 5.04 
                 4.81 
                 4.97 
                 4.49 
                 5.41 
                 4.48 
                 4.98 
                 4.57 
               
               
                 OR Quartile 4 
                 5.21 
                 3.21 
                 1.77 
                 4.85 
                 2.99 
                 1.93 
                 4.50 
                 2.79 
                 1.72 
               
               
                 p Value 
                 0.037 
                 0.031 
                 0.37 
                 0.047 
                 0.042 
                 0.31 
                 0.058 
                 0.057 
                 0.40 
               
               
                 Lower limit of 95% CI 
                 1.10 
                 1.11 
                 0.503 
                 1.02 
                 1.04 
                 0.549 
                 0.949 
                 0.971 
                 0.489 
               
               
                 Upper limit of 95% CI 
                 24.6 
                 9.24 
                 6.25 
                 22.9 
                 8.59 
                 6.78 
                 21.3 
                 7.99 
                 6.05 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 72 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0146 
                 0.0208 
                 0.0151 
                 0.0195 
                 0.0151 
                 0.0195 
               
               
                 Average 
                 0.0251 
                 0.109 
                 0.0258 
                 0.106 
                 0.0258 
                 0.106 
               
               
                 Stdev 
                 0.0349 
                 0.458 
                 0.0351 
                 0.453 
                 0.0351 
                 0.453 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.26 
                   
                 0.26 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 38 
                 41 
                 37 
                 42 
                 37 
                 42 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0146 
                 0.0182 
                 0.0146 
                 0.0182 
                 0.0146 
                 0.0182 
               
               
                 Average 
                 0.0237 
                 0.133 
                 0.0237 
                 0.133 
                 0.0237 
                 0.133 
               
               
                 Stdev 
                 0.0308 
                 0.524 
                 0.0308 
                 0.524 
                 0.0308 
                 0.524 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.26 
                   
                 0.26 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 46 
                 31 
                 46 
                 31 
                 46 
                 31 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0227 
                 0.0265 
                 0.0249 
                 0.0225 
                 0.0249 
                 0.0225 
               
               
                 Average 
                 0.0375 
                 0.132 
                 0.0395 
                 0.128 
                 0.0395 
                 0.128 
               
               
                 Stdev 
                 0.0421 
                 0.516 
                 0.0423 
                 0.508 
                 0.0423 
                 0.508 
               
               
                 p (t-test) 
                   
                 0.32 
                   
                 0.33 
                   
                 0.33 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 20 
                 32 
                 19 
                 33 
                 19 
                 33 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.59 
                 0.58 
                 0.52 
                 0.57 
                 0.58 
                 0.49 
                 0.57 
                 0.58 
                 0.49 
               
               
                 SE 
                 0.064 
                 0.067 
                 0.083 
                 0.064 
                 0.067 
                 0.084 
                 0.064 
                 0.067 
                 0.084 
               
               
                 p Value 
                 0.14 
                 0.25 
                 0.81 
                 0.25 
                 0.25 
                 0.86 
                 0.25 
                 0.25 
                 0.86 
               
               
                 nCohort Recovered 
                 38 
                 46 
                 20 
                 37 
                 46 
                 19 
                 37 
                 46 
                 19 
               
               
                 nCohort Non-recovered 
                 41 
                 31 
                 32 
                 42 
                 31 
                 33 
                 42 
                 31 
                 33 
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00449 
                 0.00202 
                 0.00202 
                 0.00449 
                 0.00202 
                 0.00202 
                 0.00449 
               
               
                 Sensitivity 
                 76% 
                 77% 
                 75% 
                 74% 
                 77% 
                 73% 
                 74% 
                 77% 
                 73% 
               
               
                 Specificity 
                 32% 
                 33% 
                 25% 
                 30% 
                 33% 
                 21% 
                 30% 
                 33% 
                 21% 
               
               
                 Cutoff Quartile 3 
                 0.0157 
                 0.0153 
                 0.0237 
                 0.0157 
                 0.0153 
                 0.0237 
                 0.0157 
                 0.0153 
                 0.0237 
               
               
                 Sensitivity 
                 56% 
                 55% 
                 50% 
                 55% 
                 55% 
                 48% 
                 55% 
                 55% 
                 48% 
               
               
                 Specificity 
                 58% 
                 54% 
                 50% 
                 57% 
                 54% 
                 47% 
                 57% 
                 54% 
                 47% 
               
               
                 Cutoff Quartile 4 
                 0.0427 
                 0.0411 
                 0.0494 
                 0.0427 
                 0.0411 
                 0.0494 
                 0.0427 
                 0.0411 
                 0.0494 
               
               
                 Sensitivity 
                 29% 
                 26% 
                 25% 
                 29% 
                 26% 
                 24% 
                 29% 
                 26% 
                 24% 
               
               
                 Specificity 
                 82% 
                 76% 
                 75% 
                 81% 
                 76% 
                 74% 
                 81% 
                 76% 
                 74% 
               
               
                 OR Quartile 2 
                 1.43 
                 1.66 
                 1.00 
                 1.19 
                 1.66 
                 0.711 
                 1.19 
                 1.66 
                 0.711 
               
               
                 p Value 
                 0.48 
                 0.34 
                 1.0 
                 0.73 
                 0.34 
                 0.62 
                 0.73 
                 0.34 
                 0.62 
               
               
                 Lower limit of 95% CI 
                 0.533 
                 0.584 
                 0.275 
                 0.445 
                 0.584 
                 0.186 
                 0.445 
                 0.584 
                 0.186 
               
               
                 Upper limit of 95% CI 
                 3.84 
                 4.71 
                 3.63 
                 3.19 
                 4.71 
                 2.72 
                 3.19 
                 4.71 
                 2.72 
               
               
                 OR Quartile 3 
                 1.76 
                 1.45 
                 1.00 
                 1.59 
                 1.45 
                 0.847 
                 1.59 
                 1.45 
                 0.847 
               
               
                 p Value 
                 0.22 
                 0.43 
                 1.0 
                 0.31 
                 0.43 
                 0.77 
                 0.31 
                 0.43 
                 0.77 
               
               
                 Lower limit of 95% CI 
                 0.720 
                 0.579 
                 0.327 
                 0.652 
                 0.579 
                 0.274 
                 0.652 
                 0.579 
                 0.274 
               
               
                 Upper limit of 95% CI 
                 4.29 
                 3.61 
                 3.06 
                 3.87 
                 3.61 
                 2.62 
                 3.87 
                 3.61 
                 2.62 
               
               
                 OR Quartile 4 
                 1.83 
                 1.11 
                 1.00 
                 1.71 
                 1.11 
                 0.896 
                 1.71 
                 1.11 
                 0.896 
               
               
                 p Value 
                 0.26 
                 0.85 
                 1.0 
                 0.32 
                 0.85 
                 0.87 
                 0.32 
                 0.85 
                 0.87 
               
               
                 Lower limit of 95% CI 
                 0.634 
                 0.387 
                 0.275 
                 0.594 
                 0.387 
                 0.245 
                 0.594 
                 0.387 
                 0.245 
               
               
                 Upper limit of 95% CI 
                 5.29 
                 3.17 
                 3.63 
                 4.95 
                 3.17 
                 3.27 
                 4.95 
                 3.17 
                 3.27 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 within 7 days after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0108 
                 0.0262 
                 0.0112 
                 0.0225 
                 0.0112 
                 0.0225 
               
               
                 Average 
                 0.0243 
                 0.133 
                 0.0245 
                 0.124 
                 0.0245 
                 0.124 
               
               
                 Stdev 
                 0.0335 
                 0.515 
                 0.0340 
                 0.494 
                 0.0340 
                 0.494 
               
               
                 p (t-test) 
                   
                 0.25 
                   
                 0.25 
                   
                 0.25 
               
               
                 Min 
                 4.13E−6 
                 6.68E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 51 
                 32 
                 48 
                 35 
                 48 
                 35 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0152 
                 0.0182 
                 0.0152 
                 0.0182 
                 0.0152 
                 0.0182 
               
               
                 Average 
                 0.0265 
                 0.171 
                 0.0267 
                 0.159 
                 0.0267 
                 0.159 
               
               
                 Stdev 
                 0.0323 
                 0.604 
                 0.0328 
                 0.581 
                 0.0328 
                 0.581 
               
               
                 p (t−test) 
                   
                 0.27 
                   
                 0.28 
                   
                 0.28 
               
               
                 Min 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
               
               
                 Max 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 58 
                 23 
                 56 
                 25 
                 56 
                 25 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 0.0155 
                 0.0170 
                 0.0142 
                 0.0190 
                 0.0147 
                 0.0173 
               
               
                 Average 
                 0.0285 
                 0.110 
                 0.0257 
                 0.114 
                 0.0262 
                 0.112 
               
               
                 Stdev 
                 0.0391 
                 0.470 
                 0.0349 
                 0.475 
                 0.0352 
                 0.469 
               
               
                 p (t−test) 
                   
                 0.29 
                   
                 0.26 
                   
                 0.27 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 6.68E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                 0.191 
                 2.98 
                 0.151 
                 2.98 
                 0.151 
                 2.98 
               
               
                 n (Patient) 
                 40 
                 39 
                 41 
                 38 
                 40 
                 39 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.64 
                 0.57 
                 0.53 
                 0.63 
                 0.57 
                 0.58 
                 0.63 
                 0.57 
                 0.56 
               
               
                 SE 
                 0.064 
                 0.072 
                 0.065 
                 0.063 
                 0.070 
                 0.065 
                 0.063 
                 0.070 
                 0.065 
               
               
                 p Value 
                 0.023 
                 0.33 
                 0.68 
                 0.044 
                 0.31 
                 0.23 
                 0.044 
                 0.31 
                 0.32 
               
               
                 nCohort Recovered 
                 51 
                 58 
                 40 
                 48 
                 56 
                 41 
                 48 
                 56 
                 40 
               
               
                 nCohort Non−recovered 
                 32 
                 23 
                 39 
                 35 
                 25 
                 38 
                 35 
                 25 
                 39 
               
               
                 Cutoff Quartile 2 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
                 0.00202 
               
               
                 Sensitivity 
                 84% 
                 78% 
                 74% 
                 83% 
                 80% 
                 76% 
                 83% 
                 80% 
                 77% 
               
               
                 Specificity 
                 35% 
                 31% 
                 30% 
                 35% 
                 32% 
                 32% 
                 35% 
                 32% 
                 32% 
               
               
                 Cutoff Quartile 3 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
                 0.0157 
               
               
                 Sensitivity 
                 66% 
                 57% 
                 51% 
                 63% 
                 56% 
                 55% 
                 63% 
                 56% 
                 54% 
               
               
                 Specificity 
                 61% 
                 53% 
                 52% 
                 60% 
                 54% 
                 56% 
                 60% 
                 54% 
                 55% 
               
               
                 Cutoff Quartile 4 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
                 0.0427 
               
               
                 Sensitivity 
                 28% 
                 30% 
                 26% 
                 29% 
                 28% 
                 29% 
                 29% 
                 28% 
                 28% 
               
               
                 Specificity 
                 78% 
                 78% 
                 78% 
                 79% 
                 77% 
                 80% 
                 79% 
                 77% 
                 80% 
               
               
                 OR Quartile 2 
                 2.95 
                 1.62 
                 1.24 
                 2.65 
                 1.89 
                 1.50 
                 2.65 
                 1.89 
                 1.60 
               
               
                 p Value 
                 0.057 
                 0.41 
                 0.67 
                 0.071 
                 0.27 
                 0.43 
                 0.071 
                 0.27 
                 0.35 
               
               
                 Lower limit of 95% CI 
                 0.967 
                 0.520 
                 0.463 
                 0.919 
                 0.613 
                 0.553 
                 0.919 
                 0.613 
                 0.593 
               
               
                 Upper limit of 95% CI 
                 8.97 
                 5.05 
                 3.33 
                 7.65 
                 5.86 
                 4.05 
                 7.65 
                 5.86 
                 4.35 
               
               
                 OR Quartile 3 
                 2.96 
                 1.49 
                 1.16 
                 2.58 
                 1.47 
                 1.58 
                 2.58 
                 1.47 
                 1.43 
               
               
                 p Value 
                 0.021 
                 0.42 
                 0.74 
                 0.038 
                 0.43 
                 0.31 
                 0.038 
                 0.43 
                 0.43 
               
               
                 Lower limit of 95% CI 
                 1.18 
                 0.564 
                 0.481 
                 1.05 
                 0.569 
                 0.649 
                 1.05 
                 0.569 
                 0.588 
               
               
                 Upper limit of 95% CI 
                 7.43 
                 3.95 
                 2.81 
                 6.33 
                 3.79 
                 3.84 
                 6.33 
                 3.79 
                 3.46 
               
               
                 OR Quartile 4 
                 1.42 
                 1.51 
                 1.19 
                 1.52 
                 1.29 
                 1.68 
                 1.52 
                 1.29 
                 1.57 
               
               
                 p Value 
                 0.50 
                 0.45 
                 0.74 
                 0.42 
                 0.64 
                 0.33 
                 0.42 
                 0.64 
                 0.40 
               
               
                 Lower limit of 95% CI 
                 0.513 
                 0.513 
                 0.423 
                 0.553 
                 0.441 
                 0.592 
                 0.553 
                 0.441 
                 0.554 
               
               
                 Upper limit of 95% CI 
                 3.94 
                 4.47 
                 3.34 
                 4.18 
                 3.75 
                 4.77 
                 4.18 
                 3.75 
                 4.46 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 12 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.55 
                 10.4 
                 7.38 
                 10.4 
                 7.25 
                 10.4 
               
               
                 Average 
                 9.81 
                 12.8 
                 9.49 
                 12.8 
                 9.59 
                 12.7 
               
               
                 Stdev 
                 7.72 
                 8.86 
                 7.79 
                 8.80 
                 7.99 
                 8.75 
               
               
                 p (t-test) 
                   
                 0.17 
                   
                 0.13 
                   
                 0.17 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 20 
                 62 
                 19 
                 63 
                 18 
                 64 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.41 
                 10.5 
                 8.41 
                 10.5 
                 8.41 
                 10.5 
               
               
                 Average 
                 11.8 
                 12.6 
                 11.9 
                 12.4 
                 11.9 
                 12.4 
               
               
                 Stdev 
                 9.26 
                 7.92 
                 9.35 
                 7.89 
                 9.35 
                 7.89 
               
               
                 p (t−test) 
                   
                 0.70 
                   
                 0.81 
                   
                 0.81 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 46 
                 35 
                 44 
                 37 
                 44 
                 37 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.72 
                 10.2 
                 7.83 
                 10.3 
                 7.56 
                 10.3 
               
               
                 Average 
                 9.64 
                 12.8 
                 9.93 
                 12.8 
                 9.61 
                 12.8 
               
               
                 Stdev 
                 6.85 
                 9.15 
                 6.82 
                 9.23 
                 6.86 
                 9.08 
               
               
                 p (t−test) 
                   
                 0.13 
                   
                 0.15 
                   
                 0.12 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 21 
                 50 
                 22 
                 49 
                 21 
                 51 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.62 
                 0.56 
                 0.61 
                 0.64 
                 0.55 
                 0.59 
                 0.64 
                 0.55 
                 0.61 
               
               
                 SE 
                 0.069 
                 0.065 
                 0.071 
                 0.068 
                 0.065 
                 0.071 
                 0.070 
                 0.065 
                 0.071 
               
               
                 p Value 
                 0.080 
                 0.33 
                 0.13 
                 0.038 
                 0.41 
                 0.21 
                 0.044 
                 0.41 
                 0.12 
               
               
                 nCohort Recovered 
                 20 
                 46 
                 21 
                 19 
                 44 
                 22 
                 18 
                 44 
                 21 
               
               
                 nCohort Non−recovered 
                 62 
                 35 
                 50 
                 63 
                 37 
                 49 
                 64 
                 37 
                 51 
               
               
                 Cutoff Quartile 2 
                 6.18 
                 6.19 
                 6.19 
                 6.18 
                 6.19 
                 6.19 
                 6.18 
                 6.19 
                 6.19 
               
               
                 Sensitivity 
                 76% 
                 80% 
                 76% 
                 76% 
                 78% 
                 76% 
                 77% 
                 78% 
                 76% 
               
               
                 Specificity 
                 30% 
                 30% 
                 29% 
                 32% 
                 30% 
                 27% 
                 33% 
                 30% 
                 29% 
               
               
                 Cutoff Quartile 3 
                 9.66 
                 9.75 
                 9.00 
                 9.66 
                 9.75 
                 9.00 
                 9.66 
                 9.75 
                 8.94 
               
               
                 Sensitivity 
                 56% 
                 57% 
                 58% 
                 57% 
                 57% 
                 57% 
                 56% 
                 57% 
                 59% 
               
               
                 Specificity 
                 70% 
                 57% 
                 71% 
                 74% 
                 57% 
                 68% 
                 72% 
                 57% 
                 71% 
               
               
                 Cutoff Quartile 4 
                 15.6 
                 15.9 
                 14.3 
                 15.6 
                 15.9 
                 14.6 
                 15.6 
                 15.9 
                 14.6 
               
               
                 Sensitivity 
                 29% 
                 31% 
                 30% 
                 30% 
                 30% 
                 29% 
                 30% 
                 30% 
                 29% 
               
               
                 Specificity 
                 85% 
                 80% 
                 86% 
                 89% 
                 80% 
                 82% 
                 89% 
                 80% 
                 86% 
               
               
                 OR Quartile 2 
                 1.34 
                 1.75 
                 1.27 
                 1.48 
                 1.52 
                 1.16 
                 1.63 
                 1.52 
                 1.30 
               
               
                 p Value 
                 0.61 
                 0.29 
                 0.69 
                 0.50 
                 0.42 
                 0.80 
                 0.40 
                 0.42 
                 0.65 
               
               
                 Lower limit of 95% CI 
                 0.439 
                 0.619 
                 0.402 
                 0.478 
                 0.550 
                 0.369 
                 0.523 
                 0.550 
                 0.413 
               
               
                 Upper limit of 95% CI 
                 4.11 
                 4.95 
                 3.99 
                 4.56 
                 4.20 
                 3.62 
                 5.10 
                 4.20 
                 4.09 
               
               
                 OR Quartile 3 
                 3.02 
                 1.73 
                 3.45 
                 3.73 
                 1.73 
                 2.86 
                 3.34 
                 1.73 
                 3.57 
               
               
                 p Value 
                 0.045 
                 0.22 
                 0.027 
                 0.023 
                 0.22 
                 0.052 
                 0.039 
                 0.22 
                 0.023 
               
               
                 Lower limit of 95% CI 
                 1.03 
                 0.713 
                 1.15 
                 1.20 
                 0.714 
                 0.989 
                 1.07 
                 0.714 
                 1.19 
               
               
                 Upper limit of 95% CI 
                 8.91 
                 4.21 
                 10.4 
                 11.6 
                 4.17 
                 8.25 
                 10.5 
                 4.17 
                 10.7 
               
               
                 OR Quartile 4 
                 2.32 
                 1.88 
                 2.57 
                 3.67 
                 1.65 
                 1.80 
                 3.38 
                 1.65 
                 2.50 
               
               
                 p Value 
                 0.22 
                 0.22 
                 0.17 
                 0.10 
                 0.34 
                 0.36 
                 0.13 
                 0.34 
                 0.19 
               
               
                 Lower limit of 95% CI 
                 0.604 
                 0.680 
                 0.658 
                 0.771 
                 0.595 
                 0.517 
                 0.706 
                 0.595 
                 0.640 
               
               
                 Upper limit of 95% CI 
                 8.89 
                 5.22 
                 10.1 
                 17.5 
                 4.55 
                 6.27 
                 16.2 
                 4.55 
                 9.77 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “recovered” and “non-recovered” cohorts where recovery starts at 
               
               
                 24 hours after sample collection and renal status is assessed by serum creatinine (sCr) 
               
               
                 only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Non- 
                   
                 Non- 
                   
                 Non- 
               
               
                 Recovery Period 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
                 Recovered 
                 recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.55 
                 10.6 
                 7.11 
                 10.6 
                 6.81 
                 10.5 
               
               
                 Average 
                 9.74 
                 13.2 
                 9.43 
                 13.2 
                 9.51 
                 13.1 
               
               
                 Stdev 
                 7.47 
                 9.15 
                 7.83 
                 8.93 
                 8.00 
                 8.88 
               
               
                 p (t-test) 
                   
                 0.078 
                   
                 0.074 
                   
                 0.097 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 26 
                 54 
                 23 
                 57 
                 22 
                 58 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.17 
                 10.7 
                 7.94 
                 11.4 
                 7.92 
                 12.0 
               
               
                 Average 
                 11.8 
                 12.7 
                 11.7 
                 12.8 
                 11.1 
                 13.6 
               
               
                 Stdev 
                 9.25 
                 8.16 
                 9.33 
                 8.05 
                 8.47 
                 9.05 
               
               
                 p (t−test) 
                   
                 0.65 
                   
                 0.58 
                   
                 0.23 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 36.8 
                 38.9 
               
               
                 n (Patient) 
                 46 
                 33 
                 45 
                 34 
                 44 
                 35 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.94 
                 10.2 
                 7.83 
                 10.3 
                 7.56 
                 10.3 
               
               
                 Average 
                 9.91 
                 13.1 
                 10.1 
                 13.0 
                 9.86 
                 13.0 
               
               
                 Stdev 
                 6.93 
                 9.44 
                 7.17 
                 9.34 
                 7.23 
                 9.18 
               
               
                 p (t−test) 
                   
                 0.12 
                   
                 0.16 
                   
                 0.13 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 25 
                 44 
                 24 
                 45 
                 23 
                 47 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 sCr or 
                   
                   
                 sCr or 
                   
                   
                 sCr or 
                   
                   
               
               
                 Duration (hr) 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
                 UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.63 
                 0.56 
                 0.60 
                 0.66 
                 0.58 
                 0.60 
                 0.66 
                 0.60 
                 0.62 
               
               
                 SE 
                 0.064 
                 0.066 
                 0.070 
                 0.064 
                 0.066 
                 0.070 
                 0.065 
                 0.065 
                 0.069 
               
               
                 p Value 
                 0.042 
                 0.33 
                 0.14 
                 0.013 
                 0.24 
                 0.16 
                 0.015 
                 0.12 
                 0.088 
               
               
                 nCohort Recovered 
                 26 
                 46 
                 25 
                 23 
                 45 
                 24 
                 22 
                 44 
                 23 
               
               
                 nCohort Non−recovered 
                 54 
                 33 
                 44 
                 57 
                 34 
                 45 
                 58 
                 35 
                 47 
               
               
                 Cutoff Quartile 2 
                 6.16 
                 6.19 
                 6.18 
                 6.16 
                 6.19 
                 6.18 
                 6.16 
                 6.19 
                 6.19 
               
               
                 Sensitivity 
                 80% 
                 79% 
                 77% 
                 81% 
                 79% 
                 78% 
                 81% 
                 80% 
                 79% 
               
               
                 Specificity 
                 35% 
                 28% 
                 32% 
                 39% 
                 29% 
                 33% 
                 41% 
                 30% 
                 35% 
               
               
                 Cutoff Quartile 3 
                 9.28 
                 9.56 
                 9.00 
                 9.28 
                 9.56 
                 9.00 
                 9.28 
                 9.56 
                 8.94 
               
               
                 Sensitivity 
                 57% 
                 58% 
                 57% 
                 60% 
                 59% 
                 58% 
                 59% 
                 60% 
                 60% 
               
               
                 Specificity 
                 65% 
                 57% 
                 64% 
                 74% 
                 58% 
                 67% 
                 73% 
                 59% 
                 70% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 16.1 
                 14.5 
                 16.0 
                 16.1 
                 14.7 
                 16.0 
                 16.1 
                 14.7 
               
               
                 Sensitivity 
                 31% 
                 33% 
                 30% 
                 30% 
                 32% 
                 27% 
                 29% 
                 34% 
                 30% 
               
               
                 Specificity 
                 88% 
                 80% 
                 84% 
                 87% 
                 80% 
                 79% 
                 86% 
                 82% 
                 83% 
               
               
                 OR Quartile 2 
                 2.07 
                 1.46 
                 1.60 
                 2.69 
                 1.57 
                 1.75 
                 2.96 
                 1.68 
                 1.97 
               
               
                 p Value 
                 0.17 
                 0.48 
                 0.40 
                 0.069 
                 0.40 
                 0.32 
                 0.048 
                 0.33 
                 0.23 
               
               
                 Lower limit of 95% CI 
                 0.728 
                 0.511 
                 0.534 
                 0.927 
                 0.547 
                 0.581 
                 1.01 
                 0.586 
                 0.653 
               
               
                 Upper limit of 95% CI 
                 5.88 
                 4.19 
                 4.79 
                 7.80 
                 4.49 
                 5.27 
                 8.66 
                 4.80 
                 5.97 
               
               
                 OR Quartile 3 
                 2.55 
                 1.76 
                 2.34 
                 4.19 
                 1.95 
                 2.74 
                 3.78 
                 2.17 
                 3.37 
               
               
                 p Value 
                 0.059 
                 0.22 
                 0.100 
                 0.0087 
                 0.15 
                 0.056 
                 0.015 
                 0.094 
                 0.025 
               
               
                 Lower limit of 95% CI 
                 0.964 
                 0.715 
                 0.851 
                 1.44 
                 0.792 
                 0.973 
                 1.29 
                 0.877 
                 1.16 
               
               
                 Upper limit of 95% CI 
                 6.73 
                 4.35 
                 6.43 
                 12.2 
                 4.83 
                 7.70 
                 11.1 
                 5.35 
                 9.74 
               
               
                 OR Quartile 4 
                 3.52 
                 2.06 
                 2.20 
                 2.83 
                 1.91 
                 1.38 
                 2.63 
                 2.35 
                 2.02 
               
               
                 p Value 
                 0.064 
                 0.17 
                 0.22 
                 0.13 
                 0.21 
                 0.59 
                 0.16 
                 0.11 
                 0.27 
               
               
                 Lower limit of 95% CI 
                 0.929 
                 0.736 
                 0.631 
                 0.742 
                 0.687 
                 0.422 
                 0.686 
                 0.833 
                 0.579 
               
               
                 Upper limit of 95% CI 
                 13.4 
                 5.74 
                 7.69 
                 10.8 
                 5.33 
                 4.52 
                 10.1 
                 6.62 
                 7.01 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 48 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  7.81 
                 10.7 
                  7.92 
                 10.4 
                  7.94 
                 10.4 
               
               
                 Average 
                  9.91 
                 14.0 
                 10.2 
                 13.4 
                 10.3 
                 13.3 
               
               
                 Stdev 
                  6.55 
                  9.69 
                  6.86 
                  9.44 
                  6.95 
                  9.38 
               
               
                 p (t-test) 
                   
                  0.035 
                   
                  0.089 
                   
                  0.11 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 36 
                 41 
                 32 
                 45 
                 31 
                 46 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.17 
                 10.6 
                  7.94 
                 10.7 
                  7.94 
                 10.7 
               
               
                 Average 
                 11.5 
                 12.4 
                 10.9 
                 13.2 
                 10.9 
                 13.2 
               
               
                 Stdev 
                  8.68 
                  7.90 
                  7.74 
                  9.08 
                  7.74 
                  9.08 
               
               
                 p (t-test) 
                   
                  0.64 
                   
                  0.24 
                   
                  0.24 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 36.8 
                 38.9 
                 36.8 
                 38.9 
               
               
                 n (Patient) 
                 46 
                 30 
                 45 
                 31 
                 45 
                 31 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.41 
                 10.4 
                  8.41 
                 10.3 
                  8.41 
                 10.2 
               
               
                 Average 
                 10.9 
                 13.9 
                 11.1 
                 13.3 
                 11.3 
                 13.1 
               
               
                 Stdev 
                  6.91 
                 10.6 
                  7.29 
                 10.0 
                  7.41 
                  9.95 
               
               
                 p (t-test) 
                   
                  0.21 
                   
                  0.35 
                   
                  0.43 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 27 
                 30 
                 23 
                 35 
                 22 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.63 
                  0.57 
                  0.56 
                  0.61 
                  0.59 
                  0.55 
                  0.60 
                  0.59 
                  0.54 
               
               
                 SE 
                  0.063 
                  0.068 
                  0.076 
                  0.065 
                  0.067 
                  0.077 
                  0.065 
                  0.067 
                  0.078 
               
               
                 p Value 
                  0.041 
                  0.34 
                  0.43 
                  0.099 
                  0.17 
                  0.51 
                  0.13 
                  0.17 
                  0.61 
               
               
                 nCohort Recovered 
                 36 
                 46 
                 27 
                 32 
                 45 
                 23 
                 31 
                 45 
                 22 
               
               
                 nCohort Non-recovered 
                 41 
                 30 
                 30 
                 45 
                 31 
                 35 
                 46 
                 31 
                 36 
               
               
                 Cutoff Quartile 2 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.29 
                  6.19 
                  6.19 
                  6.29 
               
               
                 Sensitivity 
                 80% 
                 80% 
                 77% 
                 80% 
                 81% 
                 74% 
                 80% 
                 81% 
                 75% 
               
               
                 Specificity 
                 33% 
                 28% 
                 30% 
                 34% 
                 29% 
                 26% 
                 35% 
                 29% 
                 27% 
               
               
                 Cutoff Quartile 3 
                  9.56 
                  9.28 
                  9.91 
                  9.56 
                  9.28 
                  9.74 
                  9.56 
                  9.28 
                  9.74 
               
               
                 Sensitivity 
                 61% 
                 60% 
                 57% 
                 58% 
                 61% 
                 57% 
                 57% 
                 61% 
                 56% 
               
               
                 Specificity 
                 64% 
                 57% 
                 59% 
                 62% 
                 58% 
                 61% 
                 61% 
                 58% 
                 59% 
               
               
                 Cutoff Quartile 4 
                 15.9 
                 15.0 
                 15.9 
                 15.9 
                 15.0 
                 15.6 
                 15.9 
                 15.0 
                 15.6 
               
               
                 Sensitivity 
                 32% 
                 30% 
                 30% 
                 29% 
                 32% 
                 29% 
                 28% 
                 32% 
                 28% 
               
               
                 Specificity 
                 83% 
                 78% 
                 81% 
                 81% 
                 80% 
                 78% 
                 81% 
                 80% 
                 77% 
               
               
                 OR Quartile 2 
                  2.06 
                  1.58 
                  1.38 
                  2.10 
                  1.69 
                  1.02 
                  2.26 
                  1.69 
                  1.12 
               
               
                 p Value 
                  0.17 
                  0.42 
                  0.59 
                  0.16 
                  0.35 
                  0.97 
                  0.12 
                  0.35 
                  0.85 
               
               
                 Lower limit of 95% CI 
                  0.731 
                  0.524 
                  0.424 
                  0.746 
                  0.564 
                  0.307 
                  0.803 
                  0.564 
                  0.338 
               
               
                 Upper limit of 95% CI 
                  5.82 
                  4.74 
                  4.51 
                  5.88 
                  5.08 
                  3.39 
                  6.37 
                  5.08 
                  3.75 
               
               
                 OR Quartile 3 
                  2.76 
                  1.95 
                  1.90 
                  2.28 
                  2.17 
                  2.07 
                  2.06 
                  2.17 
                  1.81 
               
               
                 p Value 
                  0.031 
                  0.16 
                  0.23 
                  0.082 
                  0.10 
                  0.18 
                  0.13 
                  0.10 
                  0.28 
               
               
                 Lower limit of 95% CI 
                  1.10 
                  0.766 
                  0.663 
                  0.901 
                  0.851 
                  0.710 
                  0.813 
                  0.851 
                  0.617 
               
               
                 Upper limit of 95% CI 
                  6.97 
                  4.96 
                  5.46 
                  5.77 
                  5.51 
                  6.06 
                  5.21 
                  5.51 
                  5.29 
               
               
                 OR Quartile 4 
                  2.32 
                  1.54 
                  1.89 
                  1.76 
                  1.90 
                  1.44 
                  1.64 
                  1.90 
                  1.31 
               
               
                 p Value 
                  0.13 
                  0.42 
                  0.32 
                  0.31 
                  0.23 
                  0.56 
                  0.38 
                  0.23 
                  0.67 
               
               
                 Lower limit of 95% CI 
                  0.776 
                  0.540 
                  0.542 
                  0.588 
                  0.667 
                  0.420 
                  0.547 
                  0.667 
                  0.380 
               
               
                 Upper limit of 95% CI 
                  6.95 
                  4.41 
                  6.56 
                  5.27 
                  5.44 
                  4.94 
                  4.92 
                  5.44 
                  4.50 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 72 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.17 
                 10.6 
                  8.41 
                 10.4 
                  8.41 
                 10.4 
               
               
                 Average 
                  9.99 
                 13.6 
                 10.1 
                 13.4 
                 10.1 
                 13.4 
               
               
                 Stdev 
                  6.20 
                  9.83 
                  6.28 
                  9.75 
                  6.28 
                  9.75 
               
               
                 p (t-test) 
                   
                  0.068 
                   
                  0.086 
                   
                  0.086 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
               
               
                 n (Patient) 
                 36 
                 38 
                 35 
                 39 
                 35 
                 39 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.17 
                 10.4 
                  8.17 
                 10.4 
                  8.17 
                 10.4 
               
               
                 Average 
                 10.8 
                 12.9 
                 10.8 
                 12.9 
                 10.8 
                 12.9 
               
               
                 Stdev 
                  7.69 
                  9.22 
                  7.69 
                  9.22 
                  7.69 
                  9.22 
               
               
                 p (t-test) 
                   
                  0.33 
                   
                  0.33 
                   
                  0.33 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 36.8 
                 38.9 
                 36.8 
                 38.9 
                 36.8 
                 38.9 
               
               
                 n (Patient) 
                 44 
                 29 
                 44 
                 29 
                 44 
                 29 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.99 
                 10.6 
                  9.56 
                 10.4 
                  9.56 
                 10.4 
               
               
                 Average 
                 10.5 
                 13.8 
                 10.7 
                 13.5 
                 10.7 
                 13.5 
               
               
                 Stdev 
                  5.62 
                 10.4 
                  5.73 
                 10.3 
                  5.73 
                 10.3 
               
               
                 p (t-test) 
                   
                  0.17 
                   
                  0.23 
                   
                  0.23 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
                 24.1 
                 38.9 
               
               
                 n (Patient) 
                 18 
                 30 
                 17 
                 31 
                 17 
                 31 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.60 
                  0.57 
                  0.56 
                  0.60 
                  0.57 
                  0.54 
                  0.60 
                  0.57 
                  0.54 
               
               
                 SE 
                  0.066 
                  0.069 
                  0.085 
                  0.066 
                  0.069 
                  0.087 
                  0.066 
                  0.069 
                  0.087 
               
               
                 p Value 
                  0.11 
                  0.29 
                  0.49 
                  0.15 
                  0.29 
                  0.62 
                  0.15 
                  0.29 
                  0.62 
               
               
                 nCohort Recovered 
                 36 
                 44 
                 18 
                 35 
                 44 
                 17 
                 35 
                 44 
                 17 
               
               
                 nCohort Non-recovered 
                 38 
                 29 
                 30 
                 39 
                 29 
                 31 
                 39 
                 29 
                 31 
               
               
                 Cutoff Quartile 2 
                  6.19 
                  6.18 
                  6.96 
                  6.19 
                  6.18 
                  6.96 
                  6.19 
                  6.18 
                  6.96 
               
               
                 Sensitivity 
                 82% 
                 79% 
                 73% 
                 82% 
                 79% 
                 74% 
                 82% 
                 79% 
                 74% 
               
               
                 Specificity 
                 33% 
                 30% 
                 22% 
                 34% 
                 30% 
                 24% 
                 34% 
                 30% 
                 24% 
               
               
                 Cutoff Quartile 3 
                  9.28 
                  9.00 
                  9.96 
                  9.28 
                  9.00 
                  9.96 
                  9.28 
                  9.00 
                  9.96 
               
               
                 Sensitivity 
                 58% 
                 59% 
                 53% 
                 56% 
                 59% 
                 52% 
                 56% 
                 59% 
                 52% 
               
               
                 Specificity 
                 58% 
                 57% 
                 56% 
                 57% 
                 57% 
                 53% 
                 57% 
                 57% 
                 53% 
               
               
                 Cutoff Quartile 4 
                 14.7 
                 14.6 
                 14.9 
                 14.7 
                 14.6 
                 14.9 
                 14.7 
                 14.6 
                 14.9 
               
               
                 Sensitivity 
                 32% 
                 31% 
                 30% 
                 31% 
                 31% 
                 29% 
                 31% 
                 31% 
                 29% 
               
               
                 Specificity 
                 81% 
                 80% 
                 83% 
                 80% 
                 80% 
                 82% 
                 80% 
                 80% 
                 82% 
               
               
                 OR Quartile 2 
                  2.21 
                  1.61 
                  0.786 
                  2.39 
                  1.61 
                  0.885 
                  2.39 
                  1.61 
                  0.885 
               
               
                 p Value 
                  0.15 
                  0.40 
                  0.73 
                  0.11 
                  0.40 
                  0.86 
                  0.11 
                  0.40 
                  0.86 
               
               
                 Lower limit of 95% CI 
                  0.757 
                  0.531 
                  0.199 
                  0.814 
                  0.531 
                  0.223 
                  0.814 
                  0.531 
                  0.223 
               
               
                 Upper limit of 95% CI 
                  6.48 
                  4.87 
                  3.11 
                  6.99 
                  4.87 
                  3.51 
                  6.99 
                  4.87 
                  3.51 
               
               
                 OR Quartile 3 
                  1.92 
                  1.86 
                  1.43 
                  1.73 
                  1.86 
                  1.20 
                  1.73 
                  1.86 
                  1.20 
               
               
                 p Value 
                  0.16 
                  0.20 
                  0.55 
                  0.25 
                  0.20 
                  0.76 
                  0.25 
                  0.20 
                  0.76 
               
               
                 Lower limit of 95% CI 
                  0.764 
                  0.721 
                  0.442 
                  0.687 
                  0.721 
                  0.367 
                  0.687 
                  0.721 
                  0.367 
               
               
                 Upper limit of 95% CI 
                  4.85 
                  4.82 
                  4.62 
                  4.34 
                  4.82 
                  3.92 
                  4.34 
                  4.82 
                  3.92 
               
               
                 OR Quartile 4 
                  1.91 
                  1.75 
                  2.14 
                  1.78 
                  1.75 
                  1.91 
                  1.78 
                  1.75 
                  1.91 
               
               
                 p Value 
                  0.24 
                  0.31 
                  0.31 
                  0.29 
                  0.31 
                  0.39 
                  0.29 
                  0.31 
                  0.39 
               
               
                 Lower limit of 95% CI 
                  0.655 
                  0.597 
                  0.495 
                  0.609 
                  0.597 
                  0.440 
                  0.609 
                  0.597 
                  0.440 
               
               
                 Upper limit of 95% CI 
                  5.59 
                  5.13 
                  9.27 
                  5.19 
                  5.13 
                  8.29 
                  5.19 
                  5.13 
                  8.29 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts within 7 days after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  9.06 
                 10.2 
                  9.06 
                 10.2 
                  9.06 
                 10.2 
               
               
                 Average 
                 11.4 
                 13.3 
                 11.4 
                 13.1 
                 11.4 
                 13.1 
               
               
                 Stdev 
                  7.18 
                 10.6 
                  7.17 
                 10.5 
                  7.17 
                 10.5 
               
               
                 p (t-test) 
                   
                  0.39 
                   
                  0.44 
                   
                  0.44 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 54 
                 30 
                 52 
                 32 
                 52 
                 32 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  9.75 
                  9.74 
                  9.16 
                  9.91 
                  9.16 
                  9.91 
               
               
                 Average 
                 12.6 
                 10.8 
                 12.5 
                 11.1 
                 12.5 
                 11.1 
               
               
                 Stdev 
                  8.99 
                  7.79 
                  9.04 
                  7.73 
                  9.04 
                  7.73 
               
               
                 p (t-test) 
                   
                  0.38 
                   
                  0.47 
                   
                  0.47 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 59 
                 22 
                 58 
                 23 
                 58 
                 23 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.48 
                 10.6 
                  8.48 
                 10.6 
                  8.41 
                 10.7 
               
               
                 Average 
                 11.0 
                 13.7 
                 10.5 
                 13.9 
                 10.5 
                 13.9 
               
               
                 Stdev 
                  7.48 
                  9.75 
                  6.64 
                  9.84 
                  6.58 
                  9.82 
               
               
                 p (t-test) 
                   
                  0.19 
                   
                  0.089 
                   
                  0.089 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 33.3 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 40 
                 38 
                 42 
                 36 
                 41 
                 37 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.53 
                  0.46 
                  0.57 
                  0.52 
                  0.48 
                  0.59 
                  0.52 
                  0.48 
                  0.59 
               
               
                 SE 
                  0.066 
                  0.073 
                  0.065 
                  0.065 
                  0.072 
                  0.065 
                  0.065 
                  0.072 
                  0.065 
               
               
                 p Value 
                  0.68 
                  0.62 
                  0.26 
                  0.78 
                  0.79 
                  0.17 
                  0.78 
                  0.79 
                  0.17 
               
               
                 nCohort Recovered 
                 54 
                 59 
                 40 
                 52 
                 58 
                 42 
                 52 
                 58 
                 41 
               
               
                 nCohort Non-recovered 
                 30 
                 22 
                 38 
                 32 
                 23 
                 36 
                 32 
                 23 
                 37 
               
               
                 Cutoff Quartile 2 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
               
               
                 Sensitivity 
                 77% 
                 77% 
                 79% 
                 75% 
                 78% 
                 81% 
                 75% 
                 78% 
                 78% 
               
               
                 Specificity 
                 26% 
                 27% 
                 32% 
                 25% 
                 28% 
                 33% 
                 25% 
                 28% 
                 32% 
               
               
                 Cutoff Quartile 3 
                  9.66 
                  9.75 
                  9.66 
                  9.66 
                  9.75 
                  9.66 
                  9.66 
                  9.75 
                  9.66 
               
               
                 Sensitivity 
                 53% 
                 50% 
                 58% 
                 53% 
                 52% 
                 58% 
                 53% 
                 52% 
                 59% 
               
               
                 Specificity 
                 52% 
                 51% 
                 57% 
                 52% 
                 52% 
                 57% 
                 52% 
                 52% 
                 59% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.6 
                 16.0 
                 15.9 
                 15.6 
                 16.0 
                 15.9 
                 15.6 
               
               
                 Sensitivity 
                 27% 
                 14% 
                 34% 
                 28% 
                 17% 
                 33% 
                 28% 
                 17% 
                 35% 
               
               
                 Specificity 
                 76% 
                 71% 
                 82% 
                 77% 
                 72% 
                 81% 
                 77% 
                 72% 
                 83% 
               
               
                 OR Quartile 2 
                  1.15 
                  1.27 
                  1.81 
                  1.00 
                  1.37 
                  2.07 
                  1.00 
                  1.37 
                  1.68 
               
               
                 p Value 
                  0.79 
                  0.69 
                  0.26 
                  1.0 
                  0.59 
                  0.17 
                  1.0 
                  0.59 
                  0.32 
               
               
                 Lower limit of 95% CI 
                  0.406 
                  0.400 
                  0.649 
                  0.362 
                  0.436 
                  0.728 
                  0.362 
                  0.436 
                  0.605 
               
               
                 Upper limit of 95% CI 
                  3.26 
                  4.00 
                  5.02 
                  2.76 
                  4.31 
                  5.89 
                  2.76 
                  4.31 
                  4.68 
               
               
                 OR Quartile 3 
                  1.23 
                  1.03 
                  1.86 
                  1.22 
                  1.17 
                  1.87 
                  1.22 
                  1.17 
                  2.07 
               
               
                 p Value 
                  0.65 
                  0.95 
                  0.18 
                  0.65 
                  0.75 
                  0.17 
                  0.65 
                  0.75 
                  0.11 
               
               
                 Lower limit of 95% CI 
                  0.503 
                  0.389 
                  0.757 
                  0.507 
                  0.445 
                  0.758 
                  0.507 
                  0.445 
                  0.839 
               
               
                 Upper limit of 95% CI 
                  3.01 
                  2.75 
                  4.57 
                  2.96 
                  3.07 
                  4.60 
                  2.96 
                  3.07 
                  5.11 
               
               
                 OR Quartile 4 
                  1.15 
                  0.390 
                  2.45 
                  1.30 
                  0.553 
                  2.12 
                  1.30 
                  0.553 
                  2.63 
               
               
                 p Value 
                  0.79 
                  0.17 
                  0.096 
                  0.60 
                  0.34 
                  0.15 
                  0.60 
                  0.34 
                  0.073 
               
               
                 Lower limit of 95% CI 
                  0.413 
                  0.102 
                  0.853 
                  0.477 
                  0.163 
                  0.754 
                  0.477 
                  0.163 
                  0.914 
               
               
                 Upper limit of 95% CI 
                  3.19 
                  1.49 
                  7.04 
                  3.56 
                  1.88 
                  5.99 
                  3.56 
                  1.88 
                  7.57 
               
               
                   
               
            
           
         
       
     
     Example 10. Use of Tyrosine-Protein Kinase Receptor UFO for Evaluating Renal Status in Patients Admitted to the ICU: Recovery to RIFLE 0 from RIFLE I and F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Tyrosine-protein kinase receptor UFO is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output during a period starting at 12, 24, 48, or 72 hours after sample collection or at any time within 7 days after sample collection. Two cohorts are defined to represent a “recovered” and a “non-recovered” population. “Recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0). “Non-recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is risk of injury (R), injury (I) or failure (F). If a patient dies or is placed on renal replacement therapy (RRT) within 9 days of enrollment, the patient is considered “non-recovered”. 
     The ability to distinguish the “recovered” and “non-recovered” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 10.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 12 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  6.03 
                  3.67 
                  5.42 
                  3.71 
                  6.03 
                  3.71 
               
               
                 Average 
                  6.95 
                  4.61 
                  5.98 
                  4.75 
                  6.82 
                  4.74 
               
               
                 Stdev 
                  2.51 
                  4.17 
                  2.14 
                  4.21 
                  2.09 
                  4.15 
               
               
                 p (t-test) 
                   
                  0.051 
                   
                  0.29 
                   
                  0.18 
               
               
                 Min 
                  3.44 
                  0.276 
                  3.44 
                  0.276 
                  4.88 
                  0.276 
               
               
                 Max 
                 10.3 
                 20.6 
                 10.3 
                 20.6 
                 10.3 
                 20.6 
               
               
                 n (Patient) 
                  8 
                 73 
                  6 
                 75 
                  4 
                 77 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  7.53 
                  2.44 
                  6.87 
                  2.51 
                  6.87 
                  2.51 
               
               
                 Average 
                  8.09 
                  2.93 
                  7.97 
                  3.20 
                  7.89 
                  3.40 
               
               
                 Stdev 
                  4.48 
                  2.25 
                  4.61 
                  2.57 
                  4.52 
                  2.94 
               
               
                 p (t-test) 
                   
                 1.1E−6 
                   
                 1.5E−5 
                   
                 6.4E−5 
               
               
                 Min 
                  0.696 
                  0.276 
                  0.696 
                  0.276 
                  0.696 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 14.5 
               
               
                 n (Patient) 
                 30 
                 51 
                 28 
                 53 
                 26 
                 55 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  3.44 
                  4.42 
                  4.16 
                  4.30 
                  3.44 
                  4.30 
               
               
                 Average 
                  3.86 
                  5.21 
                  4.05 
                  5.21 
                  3.93 
                  5.17 
               
               
                 Stdev 
                  2.86 
                  4.32 
                  2.94 
                  4.35 
                  3.07 
                  4.29 
               
               
                 p (t-test) 
                   
                  0.22 
                   
                  0.32 
                   
                  0.33 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                 10.3 
                 20.6 
                 10.3 
                 20.6 
                 10.3 
                 20.6 
               
               
                 n (Patient) 
                 11 
                 61 
                 10 
                 62 
                 9 
                 64 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.24 
                  0.12 
                  0.58 
                  0.31 
                  0.15 
                  0.56 
                  0.24 
                  0.16 
                  0.58 
               
               
                 SE 
                  0.076 
                  0.037 
                  0.090 
                  0.099 
                  0.041 
                  0.095 
                  0.10 
                  0.043 
                  0.098 
               
               
                 p Value 
                 6.7E−4 
                  0 
                  0.38 
                  0.053 
                  0 
                  0.54 
                  0.0097 
                 1.6E−15 
                  0.44 
               
               
                 nCohort Recovered 
                  8 
                 30 
                 11 
                  6 
                 28 
                 10 
                  4 
                 26 
                  9 
               
               
                 nCohort Non-recovered 
                 73 
                 51 
                 61 
                 75 
                 53 
                 62 
                 77 
                 55 
                 64 
               
               
                 Cutoff Quartile 2 
                  1.99 
                  1.99 
                  2.09 
                  1.99 
                  1.99 
                  2.09 
                  1.99 
                  1.99 
                  2.12 
               
               
                 Sensitivity 
                 71% 
                 61% 
                 77% 
                 72% 
                 62% 
                 76% 
                 73% 
                 64% 
                 77% 
               
               
                 Specificity 
                  0% 
                  3% 
                 36% 
                  0% 
                  4% 
                 30% 
                  0% 
                  4% 
                 44% 
               
               
                 Cutoff Quartile 3 
                  3.81 
                  3.81 
                  4.30 
                  3.81 
                  3.81 
                  4.30 
                  3.81 
                  3.81 
                  4.18 
               
               
                 Sensitivity 
                 45% 
                 27% 
                 51% 
                 47% 
                 30% 
                 50% 
                 47% 
                 31% 
                 50% 
               
               
                 Specificity 
                 12% 
                 13% 
                 55% 
                 17% 
                 14% 
                 50% 
                  0% 
                 12% 
                 56% 
               
               
                 Cutoff Quartile 4 
                  6.29 
                  6.29 
                  6.33 
                  6.29 
                  6.29 
                  6.33 
                  6.29 
                  6.29 
                  6.32 
               
               
                 Sensitivity 
                 22% 
                  4% 
                 26% 
                 24% 
                  8% 
                 26% 
                 23% 
                  9% 
                 25% 
               
               
                 Specificity 
                 50% 
                 40% 
                 82% 
                 67% 
                 43% 
                 80% 
                 50% 
                 42% 
                 78% 
               
               
                 OR Quartile 2 
                  0.144 
                  0.0534 
                  1.92 
                  0.195 
                  0.0611 
                  1.34 
                  0.292 
                  0.0700 
                  2.61 
               
               
                 p Value 
                  0.19 
                  0.0056 
                  0.35 
                  0.27 
                  0.0082 
                  0.69 
                  0.42 
                  0.012 
                  0.19 
               
               
                 Lower limit of 95% CI 
                  0.00793 
                  0.00674 
                  0.490 
                  0.0105 
                  0.00770 
                  0.308 
                  0.0151 
                  0.00881 
                  0.621 
               
               
                 Upper limit of 95% CI 
                  2.60 
                  0.424 
                  7.52 
                  3.61 
                  0.485 
                  5.85 
                  5.66 
                  0.556 
                 11.0 
               
               
                 OR Quartile 3 
                  0.118 
                  0.0582 
                  1.24 
                  0.175 
                  0.0721 
                  1.00 
                  0.0977 
                  0.0584 
                  1.25 
               
               
                 p Value 
                  0.051 
                 4.8E−6 
                  0.74 
                  0.12 
                 2.0E−5 
                  1.0 
                  0.12 
                 2.9E−5 
                  0.76 
               
               
                 Lower limit of 95% CI 
                  0.0138 
                  0.0172 
                  0.342 
                  0.0195 
                  0.0215 
                  0.263 
                  0.00509 
                  0.0154 
                  0.307 
               
               
                 Upper limit of 95% CI 
                  1.01 
                  0.197 
                  4.50 
                  1.57 
                  0.242 
                  3.80 
                  1.88 
                  0.221 
                  5.08 
               
               
                 OR Quartile 4 
                  0.281 
                  0.0272 
                  1.60 
                  0.632 
                  0.0612 
                  1.39 
                  0.305 
                  0.0733 
                  1.17 
               
               
                 p Value 
                  0.095 
                 9.0E−6 
                  0.57 
                  0.61 
                 1.5E−5 
                  0.69 
                  0.25 
                 2.1E−5 
                  0.86 
               
               
                 Lower limit of 95% CI 
                  0.0631 
                  0.00554 
                  0.312 
                  0.107 
                  0.0173 
                  0.267 
                  0.0401 
                  0.0220 
                  0.220 
               
               
                 Upper limit of 95% CI 
                  1.25 
                  0.134 
                  8.21 
                  3.74 
                  0.217 
                  7.25 
                  2.32 
                  0.245 
                  6.20 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 24 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  6.38 
                  3.60 
                  6.87 
                  3.52 
                  7.36 
                  3.60 
               
               
                 Average 
                  6.96 
                  4.50 
                  7.71 
                  4.51 
                  8.08 
                  4.52 
               
               
                 Stdev 
                  3.14 
                  4.16 
                  2.76 
                  4.13 
                  2.76 
                  4.10 
               
               
                 p (t-test) 
                   
                  0.042 
                   
                  0.019 
                   
                  0.019 
               
               
                 Min 
                  1.99 
                  0.276 
                  4.88 
                  0.276 
                  4.88 
                  0.276 
               
               
                 Max 
                 13.5 
                 20.6 
                 13.5 
                 20.6 
                 13.5 
                 20.6 
               
               
                 n (Patient) 
                 11 
                 69 
                  8 
                 72 
                  7 
                 73 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  6.38 
                  2.44 
                  6.35 
                  2.51 
                  6.35 
                  2.51 
               
               
                 Average 
                  7.72 
                  3.01 
                  7.58 
                  3.36 
                  7.58 
                  3.36 
               
               
                 Stdev 
                  4.54 
                  2.47 
                  4.52 
                  2.99 
                  4.52 
                  2.99 
               
               
                 p (t-test) 
                   
                 5.4E−6 
                   
                 8.7E−5 
                   
                 8.7E−5 
               
               
                 Min 
                  0.696 
                  0.276 
                  0.696 
                  0.276 
                  0.696 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 14.5 
                 20.6 
                 14.5 
               
               
                 n (Patient) 
                 31 
                 49 
                 28 
                 52 
                 28 
                 52 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.30 
                  4.30 
                  4.88 
                  4.18 
                  4.30 
                  4.18 
               
               
                 Average 
                  3.90 
                  5.11 
                  4.05 
                  5.11 
                  3.96 
                  5.07 
               
               
                 Stdev 
                  2.62 
                  4.35 
                  2.67 
                  4.38 
                  2.76 
                  4.32 
               
               
                 p (t-test) 
                   
                  0.21 
                   
                  0.28 
                   
                  0.28 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                  8.32 
                 20.6 
                  8.32 
                 20.6 
                  8.32 
                 20.6 
               
               
                 n (Patient) 
                 14 
                 54 
                 13 
                 55 
                 12 
                 57 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.26 
                  0.14 
                  0.55 
                  0.19 
                  0.17 
                  0.53 
                  0.17 
                  0.17 
                  0.55 
               
               
                 SE 
                  0.070 
                  0.041 
                  0.085 
                  0.065 
                  0.045 
                  0.088 
                  0.064 
                  0.045 
                  0.090 
               
               
                 p Value 
                 5.2E−4 
                  0 
                  0.55 
                 1.7E−6 
                 3.6E−13 
                  0.71 
                 3.1E−7 
                 3.6E−13 
                  0.61 
               
               
                 nCohort Recovered 
                 11 
                 31 
                 14 
                  8 
                 28 
                 13 
                  7 
                 28 
                 12 
               
               
                 nCohort Non-recovered 
                 69 
                 49 
                 54 
                 72 
                 52 
                 55 
                 73 
                 52 
                 57 
               
               
                 Cutoff Quartile 2 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.99 
               
               
                 Sensitivity 
                 71% 
                 61% 
                 76% 
                 72% 
                 63% 
                 76% 
                 73% 
                 63% 
                 75% 
               
               
                 Specificity 
                  0% 
                  3% 
                 29% 
                  0% 
                  4% 
                 31% 
                  0% 
                  4% 
                 33% 
               
               
                 Cutoff Quartile 3 
                  3.77 
                  3.77 
                  4.30 
                  3.77 
                  3.77 
                  4.30 
                  3.77 
                  3.77 
                  4.18 
               
               
                 Sensitivity 
                 45% 
                 27% 
                 50% 
                 44% 
                 29% 
                 49% 
                 45% 
                 29% 
                 49% 
               
               
                 Specificity 
                 18% 
                 13% 
                 50% 
                  0% 
                 11% 
                 46% 
                  0% 
                 11% 
                 50% 
               
               
                 Cutoff Quartile 4 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.29 
               
               
                 Sensitivity 
                 20% 
                  6% 
                 26% 
                 21% 
                 10% 
                 25% 
                 21% 
                 10% 
                 25% 
               
               
                 Specificity 
                 45% 
                 45% 
                 79% 
                 38% 
                 46% 
                 77% 
                 29% 
                 46% 
                 75% 
               
               
                 OR Quartile 2 
                  0.105 
                  0.0526 
                  1.26 
                  0.151 
                  0.0643 
                  1.44 
                  0.174 
                  0.0643 
                  1.54 
               
               
                 p Value 
                  0.12 
                  0.0054 
                  0.73 
                  0.20 
                  0.0095 
                  0.59 
                  0.24 
                  0.0095 
                  0.53 
               
               
                 Lower limit of 95% CI 
                  0.00591 
                  0.00662 
                  0.338 
                  0.00831 
                  0.00808 
                  0.379 
                  0.00950 
                  0.00808 
                  0.401 
               
               
                 Upper limit of 95% CI 
                  1.87 
                  0.419 
                  4.71 
                  2.73 
                  0.512 
                  5.44 
                  3.19 
                  0.512 
                  5.88 
               
               
                 OR Quartile 3 
                  0.181 
                  0.0535 
                  1.00 
                  0.0472 
                  0.0486 
                  0.827 
                  0.0551 
                  0.0486 
                  0.966 
               
               
                 p Value 
                  0.037 
                 2.9E−6 
                  1.0 
                  0.038 
                 9.7E−6 
                  0.76 
                  0.050 
                 9.7E−6 
                  0.96 
               
               
                 Lower limit of 95% CI 
                  0.0365 
                  0.0157 
                  0.309 
                  0.00263 
                  0.0127 
                  0.246 
                  0.00304 
                  0.0127 
                  0.278 
               
               
                 Upper limit of 95% CI 
                  0.901 
                  0.182 
                  3.24 
                  0.849 
                  0.186 
                  2.78 
                  1.00 
                  0.186 
                  3.35 
               
               
                 OR Quartile 4 
                  0.212 
                  0.0537 
                  1.28 
                  0.158 
                  0.0922 
                  1.14 
                  0.103 
                  0.0922 
                  0.977 
               
               
                 p Value 
                  0.022 
                 2.7E−5 
                  0.73 
                  0.019 
                 7.9E−5 
                  0.86 
                  0.010 
                 7.9E−5 
                  0.97 
               
               
                 Lower limit of 95% CI 
                  0.0564 
                  0.0137 
                  0.312 
                  0.0338 
                  0.0282 
                  0.274 
                  0.0182 
                  0.0282 
                  0.232 
               
               
                 Upper limit of 95% CI 
                  0.797 
                  0.210 
                  5.28 
                  0.737 
                  0.301 
                  4.74 
                  0.587 
                  0.301 
                  4.12 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 48 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  6.01 
                  2.51 
                  6.32 
                  2.77 
                  6.32 
                  2.77 
               
               
                 Average 
                  7.12 
                  3.91 
                  7.42 
                  3.91 
                  7.42 
                  3.91 
               
               
                 Stdev 
                  3.85 
                  3.87 
                  3.88 
                  3.81 
                  3.88 
                  3.81 
               
               
                 p (t-test) 
                   
                  0.0020 
                   
                  0.0013 
                   
                  0.0013 
               
               
                 Min 
                  2.12 
                  0.276 
                  2.12 
                  0.276 
                  2.12 
                  0.276 
               
               
                 Max 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
               
               
                 n (Patient) 
                 23 
                 57 
                 21 
                 59 
                 21 
                 59 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.77 
                  2.51 
                  5.79 
                  2.47 
                  5.79 
                  2.47 
               
               
                 Average 
                  6.84 
                  3.39 
                  7.02 
                  3.34 
                  7.02 
                  3.34 
               
               
                 Stdev 
                  4.45 
                  3.15 
                  4.40 
                  3.13 
                  4.40 
                  3.13 
               
               
                 p (t-test) 
                   
                 3.6E−4 
                   
                 1.6E−4 
                   
                 1.6E−4 
               
               
                 Min 
                  0.696 
                  0.276 
                  0.696 
                  0.276 
                  0.696 
                  0.276 
               
               
                 Max 
                 20.6 
                 14.5 
                 20.6 
                 14.5 
                 20.6 
                 14.5 
               
               
                 n (Patient) 
                 34 
                 45 
                 33 
                 46 
                 33 
                 46 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.32 
                  3.03 
                  5.19 
                  3.15 
                  5.19 
                  3.15 
               
               
                 Average 
                  5.34 
                  4.26 
                  4.90 
                  4.50 
                  4.90 
                  4.50 
               
               
                 Stdev 
                  3.35 
                  4.07 
                  2.83 
                  4.24 
                  2.83 
                  4.24 
               
               
                 p (t-test) 
                   
                  0.28 
                   
                  0.67 
                   
                  0.67 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                 0.398 
               
               
                 Max 
                 14.5 
                 20.5 
                  9.65 
                 20.5 
                  9.65 
                 20.5 
               
               
                 n (Patient) 
                 22 
                 37 
                 20 
                 40 
                 20 
                 40 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.20 
                  0.22 
                  0.37 
                  0.19 
                  0.20 
                  0.40 
                  0.19 
                  0.20 
                  0.40 
               
               
                 SE 
                  0.050 
                  0.051 
                  0.073 
                  0.048 
                  0.049 
                  0.076 
                  0.048 
                  0.049 
                  0.076 
               
               
                 p Value 
                 1.9E−9 
                 3.4E−8 
                  0.070 
                 7.1E−11 
                 5.2E−10 
                  0.21 
                 7.1E−11 
                 5.2E−10 
                  0.21 
               
               
                 nCohort Recovered 
                 23 
                 34 
                 22 
                 21 
                 33 
                 20 
                 21 
                 33 
                 20 
               
               
                 nCohort Non-recovered 
                 57 
                 45 
                 37 
                 59 
                 46 
                 40 
                 59 
                 46 
                 40 
               
               
                 Cutoff Quartile 2 
                  1.90 
                  2.05 
                  1.62 
                  1.90 
                  2.05 
                  1.63 
                  1.90 
                  2.05 
                  1.63 
               
               
                 Sensitivity 
                 65% 
                 62% 
                 68% 
                 66% 
                 61% 
                 70% 
                 66% 
                 61% 
                 70% 
               
               
                 Specificity 
                  0% 
                  9% 
                 14% 
                  0% 
                  6% 
                 15% 
                  0% 
                  6% 
                 15% 
               
               
                 Cutoff Quartile 3 
                  3.77 
                  3.81 
                  3.81 
                  3.77 
                  3.81 
                  3.77 
                  3.77 
                  3.81 
                  3.77 
               
               
                 Sensitivity 
                 35% 
                 29% 
                 41% 
                 36% 
                 28% 
                 42% 
                 36% 
                 28% 
                 42% 
               
               
                 Specificity 
                 13% 
                 24% 
                 36% 
                 10% 
                 21% 
                 35% 
                 10% 
                 21% 
                 35% 
               
               
                 Cutoff Quartile 4 
                  6.30 
                  6.30 
                  6.15 
                  6.30 
                  6.30 
                  6.08 
                  6.30 
                  6.30 
                  6.08 
               
               
                 Sensitivity 
                 16% 
                 11% 
                 22% 
                 15% 
                 11% 
                 22% 
                 15% 
                 11% 
                 22% 
               
               
                 Specificity 
                 52% 
                 56% 
                 68% 
                 48% 
                 55% 
                 70% 
                 48% 
                 55% 
                 70% 
               
               
                 OR Quartile 2 
                  0.0389 
                  0.159 
                  0.329 
                  0.0448 
                  0.100 
                  0.412 
                  0.0448 
                  0.100 
                  0.412 
               
               
                 p Value 
                  0.026 
                  0.068 
                  0.12 
                  0.033 
                  0.0036 
                  0.21 
                  0.033 
                  0.0036 
                  0.21 
               
               
                 Lower limit of 95% CI 
                  0.00225 
                  0.0422 
                  0.0812 
                  0.00258 
                  0.0214 
                  0.101 
                  0.00258 
                  0.0214 
                  0.101 
               
               
                 Upper limit of 95% CI 
                  0.675 
                  0.602 
                  1.33 
                  0.778 
                  0.472 
                  1.67 
                  0.778 
                  0.472 
                  1.67 
               
               
                 OR Quartile 3 
                  0.0811 
                  0.125 
                  0.390 
                  0.0582 
                  0.106 
                  0.398 
                  0.0582 
                  0.106 
                  0.398 
               
               
                 p Value 
                 2.1E−4 
                 6.6E−5 
                  0.090 
                 3.3E−4 
                 3.0E−5 
                  0.10 
                 3.3E−4 
                 3.0E−5 
                  0.10 
               
               
                 Lower limit of 95% CI 
                  0.0214 
                  0.0450 
                  0.131 
                  0.0123 
                  0.0370 
                  0.131 
                  0.0123 
                  0.0370 
                  0.131 
               
               
                 Upper limit of 95% CI 
                  0.307 
                  0.347 
                  1.16 
                  0.274 
                  0.304 
                  1.21 
                  0.274 
                  0.304 
                  1.21 
               
               
                 OR Quartile 4 
                  0.205 
                  0.158 
                  0.591 
                  0.164 
                  0.146 
                  0.677 
                  0.164 
                  0.146 
                  0.677 
               
               
                 p Value 
                  0.0041 
                  0.0017 
                  0.39 
                  0.0014 
                  0.0011 
                  0.53 
                  0.0014 
                  0.0011 
                  0.53 
               
               
                 Lower limit of 95% CI 
                  0.0691 
                  0.0501 
                  0.180 
                  0.0538 
                  0.0462 
                  0.202 
                  0.0538 
                  0.0462 
                  0.202 
               
               
                 Upper limit of 95% CI 
                  0.605 
                  0.500 
                  1.94 
                  0.498 
                  0.464 
                  2.27 
                  0.498 
                  0.464 
                  2.27 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 72 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.90 
                  2.77 
                  6.01 
                  2.64 
                  6.01 
                  2.64 
               
               
                 Average 
                  6.65 
                  3.65 
                  6.83 
                  3.62 
                  6.83 
                  3.62 
               
               
                 Stdev 
                  3.99 
                  3.19 
                  3.96 
                  3.16 
                  3.96 
                  3.16 
               
               
                 p (t-test) 
                   
                  0.0021 
                   
                  0.0012 
                   
                  0.0012 
               
               
                 Min 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 20.5 
                 14.5 
                 20.5 
                 14.5 
                 20.5 
                 14.5 
               
               
                 n (Patient) 
                 26 
                 53 
                 25 
                 54 
                 25 
                 54 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.58 
                  2.65 
                  5.67 
                  2.51 
                  5.67 
                  2.77 
               
               
                 Average 
                  6.10 
                  3.56 
                  6.24 
                  3.50 
                  6.27 
                  3.60 
               
               
                 Stdev 
                  3.92 
                  3.19 
                  3.89 
                  3.17 
                  3.94 
                  3.20 
               
               
                 p (t-test) 
                   
                  0.0034 
                   
                  0.0017 
                   
                  0.0029 
               
               
                 Min 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 20.5 
                 14.5 
                 20.5 
                 14.5 
                 20.5 
                 14.5 
               
               
                 n (Patient) 
                 35 
                 42 
                 34 
                 43 
                 32 
                 45 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  3.72 
                  3.03 
                  4.09 
                  2.91 
                  4.09 
                  2.91 
               
               
                 Average 
                  4.05 
                  4.06 
                  4.18 
                  4.00 
                  4.18 
                  4.00 
               
               
                 Stdev 
                  2.71 
                  3.51 
                  2.74 
                  3.48 
                  2.74 
                  3.48 
               
               
                 p (t-test) 
                   
                  0.99 
                   
                  0.85 
                   
                  0.85 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                  9.53 
                 14.5 
                  9.53 
                 14.5 
                  9.53 
                 14.5 
               
               
                 n (Patient) 
                 17 
                 35 
                 16 
                 36 
                 16 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.24 
                  0.27 
                  0.46 
                  0.22 
                  0.25 
                  0.44 
                  0.22 
                  0.26 
                  0.44 
               
               
                 SE 
                  0.054 
                  0.057 
                  0.085 
                  0.052 
                  0.055 
                  0.086 
                  0.052 
                  0.056 
                  0.086 
               
               
                 p Value 
                 1.1E−6 
                 6.3E−5 
                  0.64 
                 5.5E−8 
                 8.5E−6 
                  0.50 
                 5.5E−8 
                 2.0E−5 
                  0.50 
               
               
                 nCohort Recovered 
                 26 
                 35 
                 17 
                 25 
                 34 
                 16 
                 25 
                 32 
                 16 
               
               
                 nCohort Non-recovered 
                 53 
                 42 
                 35 
                 54 
                 43 
                 36 
                 54 
                 45 
                 36 
               
               
                 Cutoff Quartile 2 
                  1.81 
                  2.12 
                  1.56 
                  1.81 
                  2.12 
                  1.56 
                  1.81 
                  2.12 
                  1.56 
               
               
                 Sensitivity 
                 66% 
                 67% 
                 71% 
                 67% 
                 65% 
                 72% 
                 67% 
                 67% 
                 72% 
               
               
                 Specificity 
                  8% 
                 17% 
                 18% 
                  8% 
                 15% 
                 19% 
                  8% 
                 16% 
                 19% 
               
               
                 Cutoff Quartile 3 
                  3.72 
                  3.81 
                  3.36 
                  3.72 
                  3.81 
                  3.36 
                  3.72 
                  3.81 
                  3.36 
               
               
                 Sensitivity 
                 34% 
                 31% 
                 46% 
                 33% 
                 30% 
                 44% 
                 33% 
                 31% 
                 44% 
               
               
                 Specificity 
                 19% 
                 29% 
                 41% 
                 16% 
                 26% 
                 38% 
                 16% 
                 25% 
                 38% 
               
               
                 Cutoff Quartile 4 
                  6.15 
                  6.29 
                  5.39 
                  6.15 
                  6.29 
                  5.39 
                  6.15 
                  6.29 
                  5.39 
               
               
                 Sensitivity 
                 15% 
                 12% 
                 20% 
                 15% 
                 12% 
                 19% 
                 15% 
                 13% 
                 19% 
               
               
                 Specificity 
                 54% 
                 60% 
                 65% 
                 52% 
                 59% 
                 62% 
                 52% 
                 59% 
                 62% 
               
               
                 OR Quartile 2 
                  0.162 
                  0.414 
                  0.536 
                  0.174 
                  0.322 
                  0.600 
                  0.174 
                  0.370 
                  0.600 
               
               
                 p Value 
                  0.021 
                  0.11 
                  0.40 
                  0.027 
                  0.051 
                  0.49 
                  0.027 
                  0.087 
                  0.49 
               
               
                 Lower limit of 95% CI 
                  0.0344 
                  0.139 
                  0.126 
                  0.0368 
                  0.103 
                  0.140 
                  0.0368 
                  0.119 
                  0.140 
               
               
                 Upper limit of 95% CI 
                  0.764 
                  1.23 
                  2.28 
                  0.821 
                  1.00 
                  2.56 
                  0.821 
                  1.16 
                  2.56 
               
               
                 OR Quartile 3 
                  0.122 
                  0.179 
                  0.589 
                  0.0952 
                  0.156 
                  0.480 
                  0.0952 
                  0.151 
                  0.480 
               
               
                 p Value 
                 2.7E−4 
                 6.1E−4 
                  0.38 
                 1.4E−4 
                 2.8E−4 
                  0.23 
                 1.4E−4 
                 2.7E−4 
                  0.23 
               
               
                 Lower limit of 95% CI 
                  0.0396 
                  0.0671 
                  0.182 
                  0.0284 
                  0.0573 
                  0.144 
                  0.0284 
                  0.0543 
                  0.144 
               
               
                 Upper limit of 95% CI 
                  0.379 
                  0.479 
                  1.90 
                  0.319 
                  0.425 
                  1.60 
                  0.319 
                  0.417 
                  1.60 
               
               
                 OR Quartile 4 
                  0.207 
                  0.203 
                  0.458 
                  0.188 
                  0.188 
                  0.402 
                  0.188 
                  0.225 
                  0.402 
               
               
                 p Value 
                  0.0042 
                  0.0067 
                  0.24 
                  0.0026 
                  0.0046 
                  0.17 
                  0.0026 
                  0.0085 
                  0.17 
               
               
                 Lower limit of 95% CI 
                  0.0706 
                  0.0640 
                  0.126 
                  0.0636 
                  0.0592 
                  0.109 
                  0.0636 
                  0.0740 
                  0.109 
               
               
                 Upper limit of 95% CI 
                  0.609 
                  0.642 
                  1.67 
                  0.558 
                  0.597 
                  1.49 
                  0.558 
                  0.684 
                  1.49 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts within 7 days after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.58 
                  2.51 
                  5.58 
                  2.51 
                  5.58 
                  2.65 
               
               
                 Average 
                  6.47 
                  3.34 
                  6.43 
                  3.65 
                  6.38 
                  3.80 
               
               
                 Stdev 
                  4.50 
                  2.83 
                  4.34 
                  3.34 
                  4.43 
                  3.38 
               
               
                 p (t-test) 
                   
                 4.0E−4 
                   
                 0.0024 
                   
                  0.0060 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 14.5 
                 20.6 
                 14.5 
               
               
                 n (Patient) 
                 41 
                 42 
                 37 
                 46 
                 35 
                 48 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.32 
                  2.51 
                  5.32 
                  2.51 
                  5.32 
                  2.51 
               
               
                 Average 
                  6.07 
                  3.07 
                  6.10 
                  3.20 
                  6.03 
                  3.56 
               
               
                 Stdev 
                  4.53 
                  2.46 
                  4.51 
                  2.72 
                  4.40 
                  3.30 
               
               
                 p (t-test) 
                   
                 3.0E−4 
                   
                 6.8E−4 
                   
                  0.0059 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 14.5 
               
               
                 n (Patient) 
                 48 
                 33 
                 46 
                 35 
                 42 
                 39 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.16 
                  3.52 
                  5.16 
                  3.52 
                  5.19 
                  3.60 
               
               
                 Average 
                  5.76 
                  4.53 
                  5.74 
                  4.56 
                  5.76 
                  4.57 
               
               
                 Stdev 
                  4.17 
                  4.00 
                  4.17 
                  4.00 
                  4.23 
                  3.96 
               
               
                 p (t-test) 
                   
                  0.21 
                   
                  0.22 
                   
                  0.23 
               
               
                 Min 
                  0.0344 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 31 
                 48 
                 31 
                 48 
                 30 
                 49 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.26 
                  0.27 
                  0.39 
                  0.26 
                  0.27 
                  0.39 
                  0.28 
                  0.29 
                  0.39 
               
               
                 SE 
                  0.054 
                  0.059 
                  0.064 
                  0.054 
                  0.058 
                  0.064 
                  0.056 
                  0.058 
                  0.064 
               
               
                 p Value 
                 6.4E−6 
                 1.2E−4 
                  0.073 
                 1.2E−5 
                 9.7E−5 
                  0.087 
                 1.1E−4 
                 3.2E−4 
                  0.10 
               
               
                 nCohort Recovered 
                 41 
                 48 
                 31 
                 37 
                 46 
                 31 
                 35 
                 42 
                 30 
               
               
                 nCohort Non-recovered 
                 42 
                 33 
                 48 
                 46 
                 35 
                 48 
                 48 
                 39 
                 49 
               
               
                 Cutoff Quartile 2 
                  2.05 
                  1.99 
                  2.05 
                  2.05 
                  1.99 
                  2.05 
                  2.05 
                  1.99 
                  2.05 
               
               
                 Sensitivity 
                 60% 
                 64% 
                 69% 
                 61% 
                 63% 
                 69% 
                 62% 
                 64% 
                 69% 
               
               
                 Specificity 
                 10% 
                 19% 
                 16% 
                  8% 
                 17% 
                 16% 
                  9% 
                 17% 
                 17% 
               
               
                 Cutoff Quartile 3 
                  4.01 
                  3.81 
                  4.42 
                  4.01 
                  3.81 
                  4.42 
                  4.01 
                  3.81 
                  4.42 
               
               
                 Sensitivity 
                 31% 
                 27% 
                 40% 
                 33% 
                 29% 
                 42% 
                 35% 
                 31% 
                 43% 
               
               
                 Specificity 
                 32% 
                 35% 
                 35% 
                 30% 
                 35% 
                 39% 
                 31% 
                 33% 
                 40% 
               
               
                 Cutoff Quartile 4 
                  6.30 
                  6.29 
                  6.35 
                  6.30 
                  6.29 
                  6.35 
                  6.30 
                  6.29 
                  6.35 
               
               
                 Sensitivity 
                 12% 
                  6% 
                 21% 
                 15% 
                  9% 
                 21% 
                 17% 
                 13% 
                 20% 
               
               
                 Specificity 
                 61% 
                 62% 
                 68% 
                 62% 
                 63% 
                 68% 
                 63% 
                 64% 
                 67% 
               
               
                 OR Quartile 2 
                  0.159 
                  0.404 
                  0.423 
                  0.137 
                  0.356 
                  0.423 
                  0.156 
                  0.357 
                  0.453 
               
               
                 p Value 
                  0.0027 
                  0.080 
                  0.14 
                  0.0032 
                  0.049 
                  0.14 
                  0.0058 
                  0.053 
                  0.17 
               
               
                 Lower limit of 95% CI 
                  0.0478 
                  0.146 
                  0.136 
                  0.0366 
                  0.128 
                  0.136 
                  0.0417 
                  0.126 
                  0.146 
               
               
                 Upper limit of 95% CI 
                  0.529 
                  1.11 
                  1.32 
                  0.514 
                  0.993 
                  1.32 
                  0.585 
                  1.01 
                  1.41 
               
               
                 OR Quartile 3 
                  0.208 
                  0.206 
                  0.360 
                  0.205 
                  0.213 
                  0.451 
                  0.251 
                  0.222 
                  0.500 
               
               
                 p Value 
                 9.1E−4 
                  0.0014 
                  0.033 
                 9.0E−4 
                  0.0015 
                  0.091 
                  0.0035 
                  0.0016 
                  0.14 
               
               
                 Lower limit of 95% CI 
                  0.0823 
                  0.0781 
                  0.141 
                  0.0802 
                  0.0824 
                  0.179 
                  0.0995 
                  0.0873 
                  0.198 
               
               
                 Upper limit of 95% CI 
                  0.526 
                  0.541 
                  0.919 
                  0.522 
                  0.553 
                  1.14 
                  0.635 
                  0.566 
                  1.26 
               
               
                 OR Quartile 4 
                  0.211 
                  0.108 
                  0.553 
                  0.295 
                  0.160 
                  0.553 
                  0.338 
                  0.265 
                  0.513 
               
               
                 p Value 
                  0.0067 
                  0.0047 
                  0.26 
                  0.022 
                  0.0068 
                  0.26 
                  0.038 
                  0.021 
                  0.20 
               
               
                 Lower limit of 95% CI 
                  0.0685 
                  0.0229 
                  0.198 
                  0.104 
                  0.0425 
                  0.198 
                  0.122 
                  0.0854 
                  0.183 
               
               
                 Upper limit of 95% CI 
                  0.650 
                  0.504 
                  1.54 
                  0.837 
                  0.602 
                  1.54 
                  0.941 
                  0.820 
                  1.44 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 12 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.706 
                  0.614 
                  0.468 
                  0.636 
                  0.373 
                  0.640 
               
               
                 Average 
                  0.685 
                  0.887 
                  0.537 
                  0.889 
                  0.434 
                  0.890 
               
               
                 Stdev 
                  0.369 
                  0.875 
                  0.329 
                  0.859 
                  0.288 
                  0.854 
               
               
                 p (t-test) 
                   
                  0.26 
                   
                  0.11 
                   
                  0.061 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  1.22 
                  4.86 
                  0.948 
                  4.86 
                  0.881 
                  4.86 
               
               
                 n (Patient) 
                  8 
                 74 
                  5 
                 77 
                  4 
                 78 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.522 
                  0.737 
                  0.484 
                  0.737 
                  0.484 
                  0.690 
               
               
                 Average 
                  0.615 
                  1.04 
                  0.603 
                  1.03 
                  0.612 
                  1.01 
               
               
                 Stdev 
                  0.410 
                  0.990 
                  0.416 
                  0.973 
                  0.428 
                  0.961 
               
               
                 p (t-test) 
                   
                  0.010 
                   
                  0.0087 
                   
                  0.014 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.35 
                  4.86 
                  2.35 
                  4.86 
                  2.35 
                  4.86 
               
               
                 n (Patient) 
                 31 
                 50 
                 29 
                 52 
                 27 
                 54 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.915 
                  0.575 
                  0.881 
                  0.571 
                  0.817 
                  0.571 
               
               
                 Average 
                  0.880 
                  0.870 
                  0.842 
                  0.872 
                  0.829 
                  0.863 
               
               
                 Stdev 
                  0.451 
                  0.921 
                  0.460 
                  0.915 
                  0.487 
                  0.905 
               
               
                 p (t-test) 
                   
                  0.96 
                   
                  0.88 
                   
                  0.88 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  1.47 
                  4.86 
                  1.47 
                  4.86 
                  1.47 
                  4.86 
               
               
                 n (Patient) 
                 10 
                 61 
                  9 
                 62 
                  8 
                 64 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.52 
                  0.63 
                  0.38 
                  0.64 
                  0.64 
                  0.42 
                  0.72 
                  0.63 
                  0.43 
               
               
                 SE 
                  0.11 
                  0.062 
                  0.090 
                  0.12 
                  0.062 
                  0.098 
                  0.11 
                  0.064 
                  0.10 
               
               
                 p Value 
                  0.87 
                  0.039 
                  0.19 
                  0.23 
                  0.022 
                  0.39 
                  0.046 
                  0.041 
                  0.52 
               
               
                 nCohort Recovered 
                  8 
                 31 
                 10 
                  5 
                 29 
                  9 
                  4 
                 27 
                  8 
               
               
                 nCohort Non-recovered 
                 74 
                 50 
                 61 
                 77 
                 52 
                 62 
                 78 
                 54 
                 64 
               
               
                 Cutoff Quartile 2 
                  0.374 
                  0.374 
                  0.375 
                  0.374 
                  0.374 
                  0.375 
                  0.374 
                  0.374 
                  0.374 
               
               
                 Sensitivity 
                 74% 
                 78% 
                 74% 
                  75% 
                 79% 
                 74% 
                  76% 
                 78% 
                 75% 
               
               
                 Specificity 
                 25% 
                 32% 
                 20% 
                  40% 
                 34% 
                 22% 
                  50% 
                 33% 
                 25% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.636 
                  0.636 
                  0.614 
                  0.636 
                  0.593 
                  0.614 
                  0.636 
                  0.584 
               
               
                 Sensitivity 
                 50% 
                 56% 
                 46% 
                  51% 
                 56% 
                 47% 
                  51% 
                 54% 
                 48% 
               
               
                 Specificity 
                 50% 
                 61% 
                 30% 
                  60% 
                 62% 
                 33% 
                  75% 
                 59% 
                 38% 
               
               
                 Cutoff Quartile 4 
                  1.04 
                  1.04 
                  0.990 
                  1.04 
                  1.04 
                  0.990 
                  1.04 
                  1.04 
                  0.984 
               
               
                 Sensitivity 
                 26% 
                 36% 
                 23% 
                  27% 
                 35% 
                 24% 
                  27% 
                 33% 
                 23% 
               
               
                 Specificity 
                 75% 
                 94% 
                 60% 
                 100% 
                 93% 
                 67% 
                 100% 
                 93% 
                 62% 
               
               
                 OR Quartile 2 
                  0.965 
                  1.69 
                  0.703 
                  2.04 
                  1.96 
                  0.821 
                  3.11 
                  1.75 
                  1.00 
               
               
                 p Value 
                  0.97 
                  0.31 
                  0.68 
                  0.45 
                  0.19 
                  0.82 
                  0.27 
                  0.28 
                  1.0 
               
               
                 Lower limit of 95% CI 
                  0.179 
                  0.617 
                  0.135 
                  0.316 
                  0.711 
                  0.154 
                  0.409 
                  0.628 
                  0.183 
               
               
                 Upper limit of 95% CI 
                  5.19 
                  4.62 
                  3.67 
                 13.1 
                  5.41 
                  4.37 
                 23.6 
                  4.88 
                  5.46 
               
               
                 OR Quartile 3 
                  1.00 
                  2.02 
                  0.364 
                  1.54 
                  2.06 
                  0.439 
                  3.16 
                  1.69 
                  0.564 
               
               
                 p Value 
                  1.0 
                  0.13 
                  0.17 
                  0.65 
                  0.13 
                  0.27 
                  0.33 
                  0.27 
                  0.46 
               
               
                 Lower limit of 95% CI 
                  0.232 
                  0.808 
                  0.0859 
                  0.243 
                  0.815 
                  0.101 
                  0.315 
                  0.662 
                  0.124 
               
               
                 Upper limit of 95% CI 
                  4.30 
                  5.02 
                  1.54 
                  9.73 
                  5.22 
                  1.92 
                 31.7 
                  4.30 
                  2.56 
               
               
                 OR Quartile 4 
                  1.04 
                  8.16 
                  0.447 
                  4.19 
                  7.15 
                  0.638 
                  3.37 
                  6.25 
                  0.510 
               
               
                 p Value 
                  0.97 
                  0.0078 
                  0.26 
                  0.34 
                  0.013 
                  0.56 
                  0.42 
                  0.020 
                  0.39 
               
               
                 Lower limit of 95% CI 
                  0.193 
                  1.74 
                  0.110 
                  0.222 
                  1.52 
                  0.142 
                  0.174 
                  1.33 
                  0.109 
               
               
                 Upper limit of 95% CI 
                  5.58 
                 38.2 
                  1.81 
                 79.0 
                 33.5 
                  2.87 
                 65.2 
                 29.4 
                  2.39 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 24 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.724 
                  0.614 
                  0.517 
                  0.640 
                  0.517 
                  0.640 
               
               
                 Average 
                  0.809 
                  0.881 
                  0.728 
                  0.888 
                  0.755 
                  0.881 
               
               
                 Stdev 
                  0.557 
                  0.882 
                  0.594 
                  0.871 
                  0.661 
                  0.861 
               
               
                 p (t-test) 
                   
                  0.74 
                   
                  0.53 
                   
                  0.70 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.14 
                  4.86 
                  2.14 
                  4.86 
                  2.14 
                  4.86 
               
               
                 n (Patient) 
                 10 
                 70 
                  8 
                 72 
                  6 
                 74 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.567 
                  0.644 
                  0.522 
                  0.644 
                  0.545 
                  0.643 
               
               
                 Average 
                  0.685 
                  1.01 
                  0.675 
                  0.999 
                  0.687 
                  0.986 
               
               
                 Stdev 
                  0.486 
                  1.000 
                  0.498 
                  0.981 
                  0.502 
                  0.975 
               
               
                 p (t-test) 
                   
                  0.065 
                   
                  0.058 
                   
                  0.079 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.35 
                  4.86 
                  2.35 
                  4.86 
                  2.35 
                  4.86 
               
               
                 n (Patient) 
                 31 
                 48 
                 29 
                 50 
                 28 
                 51 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.754 
                  0.640 
                  0.673 
                  0.636 
                  0.593 
                  0.636 
               
               
                 Average 
                  0.923 
                  0.874 
                  0.902 
                  0.877 
                  0.898 
                  0.866 
               
               
                 Stdev 
                  0.685 
                  0.925 
                  0.704 
                  0.919 
                  0.730 
                  0.907 
               
               
                 p (t-test) 
                   
                  0.83 
                   
                  0.91 
                   
                  0.90 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 15 
                 54 
                 14 
                 55 
                 13 
                 57 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.48 
                  0.58 
                  0.42 
                  0.56 
                  0.59 
                  0.44 
                  0.56 
                  0.58 
                  0.45 
               
               
                 SE 
                  0.097 
                  0.065 
                  0.081 
                  0.10 
                  0.065 
                  0.084 
                  0.12 
                  0.066 
                  0.087 
               
               
                 p Value 
                  0.87 
                  0.23 
                  0.32 
                  0.55 
                  0.15 
                  0.50 
                  0.61 
                  0.24 
                  0.59 
               
               
                 nCohort Recovered 
                 10 
                 31 
                 15 
                  8 
                 29 
                 14 
                  6 
                 28 
                 13 
               
               
                 nCohort Non-recovered 
                 70 
                 48 
                 54 
                 72 
                 50 
                 55 
                 74 
                 51 
                 57 
               
               
                 Cutoff Quartile 2 
                  0.374 
                  0.375 
                  0.376 
                  0.374 
                  0.375 
                  0.376 
                  0.374 
                  0.375 
                  0.375 
               
               
                 Sensitivity 
                 76% 
                 77% 
                 72% 
                 76% 
                 78% 
                 73% 
                 76% 
                 76% 
                 74% 
               
               
                 Specificity 
                 30% 
                 29% 
                 20% 
                 38% 
                 31% 
                 21% 
                 33% 
                 29% 
                 23% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.636 
                  0.643 
                  0.614 
                  0.636 
                  0.636 
                  0.614 
                  0.636 
                  0.614 
               
               
                 Sensitivity 
                 50% 
                 52% 
                 48% 
                 51% 
                 52% 
                 49% 
                 51% 
                 51% 
                 51% 
               
               
                 Specificity 
                 50% 
                 55% 
                 47% 
                 62% 
                 55% 
                 50% 
                 67% 
                 54% 
                 54% 
               
               
                 Cutoff Quartile 4 
                  1.04 
                  1.04 
                  1.00 
                  1.04 
                  1.04 
                  1.00 
                  1.04 
                  1.04 
                  0.995 
               
               
                 Sensitivity 
                 24% 
                 33% 
                 22% 
                 26% 
                 34% 
                 24% 
                 26% 
                 33% 
                 25% 
               
               
                 Specificity 
                 70% 
                 87% 
                 67% 
                 88% 
                 90% 
                 71% 
                 83% 
                 89% 
                 69% 
               
               
                 OR Quartile 2 
                  1.34 
                  1.38 
                  0.650 
                  1.94 
                  1.60 
                  0.727 
                  1.56 
                  1.30 
                  0.840 
               
               
                 p Value 
                  0.70 
                  0.54 
                  0.55 
                  0.40 
                  0.38 
                  0.66 
                  0.63 
                  0.62 
                  0.81 
               
               
                 Lower limit of 95% CI 
                  0.311 
                  0.493 
                  0.161 
                  0.420 
                  0.568 
                  0.178 
                  0.263 
                  0.457 
                  0.203 
               
               
                 Upper limit of 95% CI 
                  5.75 
                  3.84 
                  2.63 
                  8.98 
                  4.48 
                  2.97 
                  9.21 
                  3.69 
                  3.47 
               
               
                 OR Quartile 3 
                  1.00 
                  1.32 
                  0.812 
                  1.76 
                  1.33 
                  0.964 
                  2.11 
                  1.20 
                  1.21 
               
               
                 p Value 
                  1.0 
                  0.55 
                  0.72 
                  0.46 
                  0.54 
                  0.95 
                  0.40 
                  0.70 
                  0.76 
               
               
                 Lower limit of 95% CI 
                  0.266 
                  0.533 
                  0.258 
                  0.392 
                  0.532 
                  0.298 
                  0.364 
                  0.477 
                  0.361 
               
               
                 Upper limit of 95% CI 
                  3.76 
                  3.27 
                  2.56 
                  7.93 
                  3.34 
                  3.12 
                 12.2 
                  3.02 
                  4.04 
               
               
                 OR Quartile 4 
                  0.748 
                  3.38 
                  0.571 
                  2.51 
                  4.46 
                  0.774 
                  1.73 
                  4.17 
                  0.733 
               
               
                 p Value 
                  0.70 
                  0.049 
                  0.38 
                  0.40 
                  0.028 
                  0.70 
                  0.63 
                  0.036 
                  0.64 
               
               
                 Lower limit of 95% CI 
                  0.174 
                  1.01 
                  0.164 
                  0.289 
                  1.18 
                  0.208 
                  0.190 
                  1.10 
                  0.195 
               
               
                 Upper limit of 95% CI 
                  3.22 
                 11.3 
                  2.00 
                 21.8 
                 16.9 
                  2.88 
                 15.7 
                 15.8 
                  2.75 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and  
               
               
                 “non-recovered” cohorts where recovery starts at 48 hours after sample collection and renal status is assessed by serum 
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.567 
                  0.614 
                  0.625 
                  0.593 
                  0.625 
                  0.593 
               
               
                 Average 
                  0.692 
                  0.915 
                  0.725 
                  0.894 
                  0.725 
                  0.894 
               
               
                 Stdev 
                  0.563 
                  0.923 
                  0.587 
                  0.907 
                  0.587 
                  0.907 
               
               
                 p (t-test) 
                   
                  0.21 
                   
                  0.37 
                   
                  0.37 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 21 
                 56 
                 18 
                 59 
                 18 
                 59 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.503 
                  0.644 
                  0.522 
                  0.643 
                  0.522 
                  0.643 
               
               
                 Average 
                  0.674 
                  0.988 
                  0.685 
                  0.973 
                  0.685 
                  0.973 
               
               
                 Stdev 
                  0.578 
                  0.983 
                  0.584 
                  0.977 
                  0.584 
                  0.977 
               
               
                 p (t-test) 
                   
                  0.090 
                   
                  0.12 
                   
                  0.12 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 32 
                 44 
                 31 
                 45 
                 31 
                 45 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.718 
                  0.532 
                  0.718 
                  0.553 
                  0.718 
                  0.553 
               
               
                 Average 
                  0.857 
                  0.880 
                  0.865 
                  0.859 
                  0.865 
                  0.859 
               
               
                 Stdev 
                  0.604 
                  0.879 
                  0.634 
                  0.853 
                  0.634 
                  0.853 
               
               
                 p (t-test) 
                   
                  0.91 
                   
                  0.98 
                   
                  0.98 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.60 
                  2.99 
                  4.60 
                  2.99 
                  4.60 
               
               
                 n (Patient) 
                 20 
                 37 
                 18 
                 40 
                 18 
                 40 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.55 
                  0.61 
                  0.43 
                  0.51 
                  0.59 
                  0.43 
                  0.51 
                  0.59 
                  0.43 
               
               
                 SE 
                  0.073 
                  0.065 
                  0.079 
                  0.078 
                  0.066 
                  0.080 
                  0.078 
                  0.066 
                  0.080 
               
               
                 p Value 
                  0.53 
                  0.094 
                  0.34 
                  0.89 
                  0.16 
                  0.36 
                  0.89 
                  0.16 
                  0.36 
               
               
                 nCohort Recovered 
                 21 
                 32 
                 20 
                 18 
                 31 
                 18 
                 18 
                 31 
                 18 
               
               
                 nCohort Non-recovered 
                 56 
                 44 
                 37 
                 59 
                 45 
                 40 
                 59 
                 45 
                 40 
               
               
                 Cutoff Quartile 2 
                  0.374 
                  0.374 
                  0.389 
                  0.374 
                  0.374 
                  0.379 
                  0.374 
                  0.374 
                  0.379 
               
               
                 Sensitivity 
                 73% 
                 80% 
                 68% 
                 71% 
                 78% 
                 70% 
                 71% 
                 78% 
                 70% 
               
               
                 Specificity 
                 24% 
                 31% 
                 15% 
                 17% 
                 29% 
                 17% 
                 17% 
                 29% 
                 17% 
               
               
                 Cutoff Quartile 3 
                  0.593 
                  0.584 
                  0.636 
                  0.593 
                  0.584 
                  0.614 
                  0.593 
                  0.584 
                  0.614 
               
               
                 Sensitivity 
                 50% 
                 57% 
                 46% 
                 49% 
                 56% 
                 48% 
                 49% 
                 56% 
                 48% 
               
               
                 Specificity 
                 52% 
                 59% 
                 45% 
                 50% 
                 58% 
                 44% 
                 50% 
                 58% 
                 44% 
               
               
                 Cutoff Quartile 4 
                  1.00 
                  1.01 
                  1.07 
                  1.00 
                  1.01 
                  1.06 
                  1.00 
                  1.01 
                  1.06 
               
               
                 Sensitivity 
                 32% 
                 36% 
                 24% 
                 31% 
                 36% 
                 25% 
                 31% 
                 36% 
                 25% 
               
               
                 Specificity 
                 95% 
                 91% 
                 75% 
                 94% 
                 90% 
                 72% 
                 94% 
                 90% 
                 72% 
               
               
                 OR Quartile 2 
                  0.854 
                  1.77 
                  0.368 
                  0.494 
                  1.43 
                  0.467 
                  0.494 
                  1.43 
                  0.467 
               
               
                 p Value 
                  0.79 
                  0.29 
                  0.16 
                  0.31 
                  0.50 
                  0.29 
                  0.31 
                  0.50 
                  0.29 
               
               
                 Lower limit of 95% CI 
                  0.266 
                  0.621 
                  0.0900 
                  0.127 
                  0.503 
                  0.114 
                  0.127 
                  0.503 
                  0.114 
               
               
                 Upper limit of 95% CI 
                  2.74 
                  5.03 
                  1.50 
                  1.93 
                  4.08 
                  1.92 
                  1.93 
                  4.08 
                  1.92 
               
               
                 OR Quartile 3 
                  1.10 
                  1.92 
                  0.695 
                  0.967 
                  1.73 
                  0.724 
                  0.967 
                  1.73 
                  0.724 
               
               
                 p Value 
                  0.85 
                  0.17 
                  0.51 
                  0.95 
                  0.24 
                  0.57 
                  0.95 
                  0.24 
                  0.57 
               
               
                 Lower limit of 95% CI 
                  0.403 
                  0.763 
                  0.233 
                  0.336 
                  0.687 
                  0.237 
                  0.336 
                  0.687 
                  0.237 
               
               
                 Upper limit of 95% CI 
                  3.00 
                  4.84 
                  2.07 
                  2.78 
                  4.36 
                  2.21 
                  2.78 
                  4.36 
                  2.21 
               
               
                 OR Quartile 4 
                  9.47 
                  5.52 
                  0.964 
                  7.46 
                  5.15 
                  0.867 
                  7.46 
                  5.15 
                  0.867 
               
               
                 p Value 
                  0.035 
                  0.012 
                  0.95 
                  0.060 
                  0.016 
                  0.82 
                  0.060 
                  0.016 
                  0.82 
               
               
                 Lower limit of 95% CI 
                  1.18 
                  1.45 
                  0.273 
                  0.922 
                  1.35 
                  0.247 
                  0.922 
                  1.35 
                  0.247 
               
               
                 Upper limit of 95% CI 
                 76.2 
                 21.1 
                  3.40 
                 60.4 
                 19.6 
                  3.04 
                 60.4 
                 19.6 
                  3.04 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 72 hours after sample collection and renal status is assessed by  
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.669 
                  0.584 
                  0.669 
                  0.584 
                  0.669 
                  0.584 
               
               
                 Average 
                  0.832 
                  0.883 
                  0.832 
                  0.883 
                  0.832 
                  0.883 
               
               
                 Stdev 
                  0.672 
                  0.927 
                  0.672 
                  0.927 
                  0.672 
                  0.927 
               
               
                 p (t-test) 
                   
                  0.80 
                   
                  0.80 
                   
                  0.80 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 22 
                 52 
                 22 
                 52 
                 22 
                 52 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.567 
                  0.614 
                  0.567 
                  0.614 
                  0.656 
                  0.584 
               
               
                 Average 
                  0.779 
                  0.927 
                  0.782 
                  0.917 
                  0.818 
                  0.888 
               
               
                 Stdev 
                  0.650 
                  0.999 
                  0.663 
                  0.980 
                  0.671 
                  0.967 
               
               
                 p (t-test) 
                   
                  0.46 
                   
                  0.49 
                   
                  0.72 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 33 
                 40 
                 31 
                 42 
                 29 
                 44 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.625 
                  0.605 
                  0.625 
                  0.605 
                  0.625 
                  0.605 
               
               
                 Average 
                  0.752 
                  0.880 
                  0.752 
                  0.880 
                  0.752 
                  0.880 
               
               
                 Stdev 
                  0.372 
                  0.871 
                  0.372 
                  0.871 
                  0.372 
                  0.871 
               
               
                 p (t-test) 
                   
                  0.49 
                   
                  0.49 
                   
                  0.49 
               
               
                 Min 
                  0.279 
                  0.172 
                  0.279 
                  0.172 
                  0.279 
                  0.172 
               
               
                 Max 
                  1.47 
                  4.60 
                  1.47 
                  4.60 
                  1.47 
                  4.60 
               
               
                 n (Patient) 
                 14 
                 34 
                 14 
                 34 
                 14 
                 34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.48 
                  0.53 
                  0.45 
                  0.48 
                  0.53 
                  0.45 
                  0.48 
                  0.48 
                  0.45 
               
               
                 SE 
                  0.073 
                  0.068 
                  0.091 
                  0.073 
                  0.069 
                  0.091 
                  0.073 
                  0.069 
                  0.091 
               
               
                 p Value 
                  0.78 
                  0.67 
                  0.59 
                  0.78 
                  0.69 
                  0.59 
                  0.78 
                  0.82 
                  0.59 
               
               
                 nCohort Recovered 
                 22 
                 33 
                 14 
                 22 
                 31 
                 14 
                 22 
                 29 
                 14 
               
               
                 nCohort Non-recovered 
                 52 
                 40 
                 34 
                 52 
                 42 
                 34 
                 52 
                 44 
                 34 
               
               
                 Cutoff Quartile 2 
                  0.375 
                  0.374 
                  0.397 
                  0.375 
                  0.374 
                  0.397 
                  0.375 
                  0.374 
                  0.397 
               
               
                 Sensitivity 
                 73% 
                 75% 
                 71% 
                 73% 
                 74% 
                 71% 
                 73% 
                 70% 
                 71% 
               
               
                 Specificity 
                 23% 
                 27% 
                 14% 
                 23% 
                 26% 
                 14% 
                 23% 
                 21% 
                 14% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.593 
                  0.614 
                  0.614 
                  0.593 
                  0.614 
                  0.614 
                  0.593 
                  0.614 
               
               
                 Sensitivity 
                 48% 
                 50% 
                 50% 
                 48% 
                 50% 
                 50% 
                 48% 
                 48% 
                 50% 
               
               
                 Specificity 
                 45% 
                 52% 
                 50% 
                 45% 
                 52% 
                 50% 
                 45% 
                 48% 
                 50% 
               
               
                 Cutoff Quartile 4 
                  1.03 
                  1.00 
                  1.05 
                  1.03 
                  1.00 
                  1.05 
                  1.03 
                  1.00 
                  1.05 
               
               
                 Sensitivity 
                 29% 
                 30% 
                 26% 
                 29% 
                 31% 
                 26% 
                 29% 
                 30% 
                 26% 
               
               
                 Specificity 
                 82% 
                 82% 
                 79% 
                 82% 
                 84% 
                 79% 
                 82% 
                 83% 
                 79% 
               
               
                 OR Quartile 2 
                  0.798 
                  1.12 
                  0.400 
                  0.798 
                  0.980 
                  0.400 
                  0.798 
                  0.622 
                  0.400 
               
               
                 p Value 
                  0.71 
                  0.83 
                  0.28 
                  0.71 
                  0.97 
                  0.28 
                  0.71 
                  0.40 
                  0.28 
               
               
                 Lower limit of 95% CI 
                  0.248 
                  0.394 
                  0.0754 
                  0.248 
                  0.340 
                  0.0754 
                  0.248 
                  0.206 
                  0.0754 
               
               
                 Upper limit of 95% CI 
                  2.57 
                  3.21 
                  2.12 
                  2.57 
                  2.83 
                  2.12 
                  2.57 
                  1.88 
                  2.12 
               
               
                 OR Quartile 3 
                  0.772 
                  1.06 
                  1.00 
                  0.772 
                  1.07 
                  1.00 
                  0.772 
                  0.852 
                  1.00 
               
               
                 p Value 
                  0.61 
                  0.90 
                  1.0 
                  0.61 
                  0.89 
                  1.0 
                  0.61 
                  0.74 
                  1.0 
               
               
                 Lower limit of 95% CI 
                  0.284 
                  0.423 
                  0.288 
                  0.284 
                  0.421 
                  0.288 
                  0.284 
                  0.333 
                  0.288 
               
               
                 Upper limit of 95% CI 
                  2.10 
                  2.67 
                  3.47 
                  2.10 
                  2.70 
                  3.47 
                  2.10 
                  2.18 
                  3.47 
               
               
                 OR Quartile 4 
                  1.82 
                  1.93 
                  1.32 
                  1.82 
                  2.33 
                  1.32 
                  1.82 
                  2.01 
                  1.32 
               
               
                 p Value 
                  0.34 
                  0.25 
                  0.71 
                  0.34 
                  0.15 
                  0.71 
                  0.34 
                  0.24 
                  0.71 
               
               
                 Lower limit of 95% CI 
                  0.529 
                  0.633 
                  0.298 
                  0.529 
                  0.731 
                  0.298 
                  0.529 
                  0.630 
                  0.298 
               
               
                 Upper limit of 95% CI 
                  6.29 
                  5.87 
                  5.84 
                  6.29 
                  7.43 
                  5.84 
                  6.29 
                  6.43 
                  5.84 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts within 7 days after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.602 
                  0.618 
                  0.612 
                  0.614 
                  0.561 
                  0.640 
               
               
                 Average 
                  0.845 
                  0.874 
                  0.875 
                  0.844 
                  0.869 
                  0.851 
               
               
                 Stdev 
                  0.838 
                  0.827 
                  0.872 
                  0.796 
                  0.894 
                  0.779 
               
               
                 p (t-test) 
                   
                  0.88 
                   
                  0.87 
                   
                  0.92 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 44 
                 40 
                 40 
                 44 
                 38 
                 46 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.561 
                  0.644 
                  0.602 
                  0.643 
                  0.539 
                  0.644 
               
               
                 Average 
                  0.845 
                  0.919 
                  0.865 
                  0.889 
                  0.862 
                  0.889 
               
               
                 Stdev 
                  0.847 
                  0.836 
                  0.860 
                  0.821 
                  0.897 
                  0.781 
               
               
                 p (t-test) 
                   
                  0.71 
                   
                  0.90 
                   
                  0.89 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 48 
                 33 
                 46 
                 35 
                 42 
                 39 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.580 
                  0.609 
                  0.593 
                  0.575 
                  0.580 
                  0.609 
               
               
                 Average 
                  0.753 
                  0.906 
                  0.746 
                  0.909 
                  0.739 
                  0.910 
               
               
                 Stdev 
                  0.537 
                  0.979 
                  0.533 
                  0.989 
                  0.541 
                  0.979 
               
               
                 p (t-test) 
                   
                  0.38 
                   
                  0.35 
                   
                  0.33 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 30 
                 48 
                 31 
                 47 
                 30 
                 48 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.51 
                  0.56 
                  0.47 
                  0.49 
                  0.53 
                  0.47 
                  0.51 
                  0.56 
                  0.49 
               
               
                 SE 
                  0.063 
                  0.066 
                  0.067 
                  0.063 
                  0.065 
                  0.067 
                  0.064 
                  0.064 
                  0.067 
               
               
                 p Value 
                  0.94 
                  0.39 
                  0.67 
                  0.86 
                  0.61 
                  0.71 
                  0.87 
                  0.32 
                  0.84 
               
               
                 nCohort Recovered 
                 44 
                 48 
                 30 
                 40 
                 46 
                 31 
                 38 
                 42 
                 30 
               
               
                 nCohort Non-recovered 
                 40 
                 33 
                 48 
                 44 
                 35 
                 47 
                 46 
                 39 
                 48 
               
               
                 Cutoff Quartile 2 
                  0.372 
                  0.374 
                  0.375 
                  0.372 
                  0.374 
                  0.374 
                  0.372 
                  0.374 
                  0.374 
               
               
                 Sensitivity 
                 72% 
                 79% 
                 69% 
                 73% 
                 77% 
                 70% 
                 74% 
                 79% 
                 71% 
               
               
                 Specificity 
                 23% 
                 29% 
                 17% 
                 22% 
                 28% 
                 19% 
                 24% 
                 31% 
                 20% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.636 
                  0.584 
                  0.614 
                  0.636 
                  0.584 
                  0.614 
                  0.636 
                  0.584 
               
               
                 Sensitivity 
                 50% 
                 55% 
                 50% 
                 50% 
                 51% 
                 49% 
                 52% 
                 54% 
                 50% 
               
               
                 Specificity 
                 50% 
                 54% 
                 50% 
                 50% 
                 52% 
                 48% 
                 53% 
                 55% 
                 50% 
               
               
                 Cutoff Quartile 4 
                  1.04 
                  1.04 
                  0.995 
                  1.04 
                  1.04 
                  0.995 
                  1.04 
                  1.04 
                  0.995 
               
               
                 Sensitivity 
                 30% 
                 30% 
                 29% 
                 27% 
                 29% 
                 30% 
                 28% 
                 28% 
                 29% 
               
               
                 Specificity 
                 80% 
                 79% 
                 80% 
                 78% 
                 78% 
                 81% 
                 79% 
                 79% 
                 80% 
               
               
                 OR Quartile 2 
                  0.775 
                  1.53 
                  0.440 
                  0.774 
                  1.33 
                  0.566 
                  0.879 
                  1.74 
                  0.607 
               
               
                 p Value 
                  0.61 
                  0.42 
                  0.16 
                  0.61 
                  0.58 
                  0.30 
                  0.80 
                  0.29 
                  0.37 
               
               
                 Lower limit of 95% CI 
                  0.288 
                  0.540 
                  0.141 
                  0.286 
                  0.481 
                  0.190 
                  0.325 
                  0.629 
                  0.204 
               
               
                 Upper limit of 95% CI 
                  2.09 
                  4.33 
                  1.37 
                  2.09 
                  3.68 
                  1.68 
                  2.38 
                  4.80 
                  1.81 
               
               
                 OR Quartile 3 
                  1.00 
                  1.42 
                  1.00 
                  1.00 
                  1.16 
                  0.898 
                  1.21 
                  1.41 
                  1.00 
               
               
                 p Value 
                  1.0 
                  0.44 
                  1.0 
                  1.0 
                  0.75 
                  0.82 
                  0.66 
                  0.44 
                  1.0 
               
               
                 Lower limit of 95% CI 
                  0.425 
                  0.582 
                  0.402 
                  0.425 
                  0.479 
                  0.363 
                  0.513 
                  0.589 
                  0.402 
               
               
                 Upper limit of 95% CI 
                  2.35 
                  3.45 
                  2.49 
                  2.35 
                  2.78 
                  2.23 
                  2.87 
                  3.39 
                  2.49 
               
               
                 OR Quartile 4 
                  1.67 
                  1.65 
                  1.65 
                  1.29 
                  1.44 
                  1.77 
                  1.48 
                  1.44 
                  1.65 
               
               
                 p Value 
                  0.32 
                  0.33 
                  0.37 
                  0.61 
                  0.48 
                  0.30 
                  0.45 
                  0.48 
                  0.37 
               
               
                 Lower limit of 95% CI 
                  0.615 
                  0.597 
                  0.554 
                  0.477 
                  0.522 
                  0.595 
                  0.538 
                  0.522 
                  0.554 
               
               
                 Upper limit of 95% CI 
                  4.52 
                  4.57 
                  4.90 
                  3.50 
                  3.97 
                  5.25 
                  4.06 
                  3.97 
                  4.90 
               
               
                   
               
            
           
         
       
     
     Example 11. Use of Tyrosine-Protein Kinase Receptor UFO for Evaluating Renal Status in Patients Admitted to the ICU: Recovery to RIFLE 0 and R from RIFLE I and F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Tyrosine-protein kinase receptor UFO is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output during a period starting at 12, 24, 48, or 72 hours after sample collection or at any time within 7 days after sample collection. Two cohorts are defined to represent a “recovered” and a “non-recovered” population. “Recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0) or risk of injury (R). “Non-recovered” indicates those patients whose maximum RIFLE stage during a period of 24, 48 or 72 hours is injury (I) or failure (F). If a patient dies or is placed on renal replacement therapy (RRT) within 9 days of enrollment, the patient is considered “non-recovered”. 
     The ability to distinguish the “recovered” and “non-recovered” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 11.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 12 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.79 
                  3.52 
                  5.74 
                  3.60 
                  5.69 
                  3.64 
               
               
                 Average 
                  6.19 
                  4.43 
                  5.96 
                  4.53 
                  5.46 
                  4.68 
               
               
                 Stdev 
                  3.26 
                  4.24 
                  3.19 
                  4.27 
                  2.51 
                  4.41 
               
               
                 p (t-test) 
                   
                  0.070 
                   
                  0.14 
                   
                  0.36 
               
               
                 Min 
                  1.99 
                  0.276 
                  1.99 
                  0.276 
                  1.99 
                  0.276 
               
               
                 Max 
                 14.5 
                 20.6 
                 14.5 
                 20.6 
                 10.3 
                 20.6 
               
               
                 n (Patient) 
                 19 
                 62 
                 18 
                 63 
                 17 
                 64 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.58 
                  2.32 
                  5.58 
                  2.47 
                  5.58 
                  2.47 
               
               
                 Average 
                  6.33 
                  2.79 
                  6.31 
                  3.02 
                  6.31 
                  3.02 
               
               
                 Stdev 
                  4.42 
                  2.41 
                  4.45 
                  2.65 
                  4.45 
                  2.65 
               
               
                 p (t-test) 
                   
                 2.0E−5 
                   
                 1.1E−4 
                   
                 1.1E−4 
               
               
                 Min 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 47 
                 34 
                 45 
                 36 
                 45 
                 36 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.74 
                  4.09 
                  4.88 
                  4.01 
                  4.21 
                  4.18 
               
               
                 Average 
                  4.87 
                  5.05 
                  5.13 
                  5.01 
                  4.29 
                  5.29 
               
               
                 Stdev 
                  3.50 
                  4.39 
                  3.61 
                  4.42 
                  2.74 
                  4.58 
               
               
                 p (t-test) 
                   
                  0.86 
                   
                  0.91 
                   
                  0.27 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                 14.5 
                 20.6 
                 14.5 
                 20.6 
                 10.3 
                 20.6 
               
               
                 n (Patient) 
                 20 
                 52 
                 21 
                 51 
                 20 
                 53 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.30 
                  0.21 
                  0.48 
                  0.33 
                  0.23 
                  0.46 
                  0.35 
                  0.23 
                  0.53 
               
               
                 SE 
                  0.064 
                  0.053 
                  0.076 
                  0.067 
                  0.054 
                  0.074 
                  0.071 
                  0.054 
                  0.076 
               
               
                 p Value 
                  0.0021 
                 6.9E−8 
                  0.83 
                  0.0094 
                 9.1E−7 
                  0.58 
                  0.039 
                 9.1E−7 
                  0.73 
               
               
                 nCohort Recovered 
                 19 
                 47 
                 20 
                 18 
                 45 
                 21 
                 17 
                 45 
                 20 
               
               
                 nCohort Non-recovered 
                 62 
                 34 
                 52 
                 63 
                 36 
                 51 
                 64 
                 36 
                 53 
               
               
                 Cutoff Quartile 2 
                  1.99 
                  1.99 
                  2.09 
                  1.99 
                  1.99 
                  2.09 
                  1.99 
                  1.99 
                  2.12 
               
               
                 Sensitivity 
                 68% 
                 56% 
                 75% 
                 68% 
                 58% 
                 75% 
                 69% 
                 58% 
                 75% 
               
               
                 Specificity 
                  5% 
                 13% 
                 25% 
                  6% 
                 13% 
                 24% 
                  6% 
                 13% 
                 30% 
               
               
                 Cutoff Quartile 3 
                  3.81 
                  3.81 
                  4.30 
                  3.81 
                  3.81 
                  4.30 
                  3.81 
                  3.81 
                  4.18 
               
               
                 Sensitivity 
                 44% 
                 24% 
                 48% 
                 44% 
                 25% 
                 47% 
                 45% 
                 25% 
                 49% 
               
               
                 Specificity 
                 32% 
                 32% 
                 45% 
                 33% 
                 31% 
                 43% 
                 35% 
                 31% 
                 50% 
               
               
                 Cutoff Quartile 4 
                  6.29 
                  6.29 
                  6.33 
                  6.29 
                  6.29 
                  6.33 
                  6.29 
                  6.29 
                  6.32 
               
               
                 Sensitivity 
                 21% 
                  6% 
                 25% 
                 22% 
                  8% 
                 24% 
                 23% 
                  8% 
                 26% 
               
               
                 Specificity 
                 63% 
                 62% 
                 75% 
                 67% 
                 62% 
                 71% 
                 71% 
                 62% 
                 80% 
               
               
                 OR Quartile 2 
                  0.117 
                  0.185 
                  1.00 
                  0.126 
                  0.215 
                  0.913 
                  0.138 
                  0.215 
                  1.32 
               
               
                 p Value 
                  0.043 
                  0.0025 
                  1.0 
                  0.052 
                  0.0056 
                  0.88 
                  0.063 
                  0.0056 
                  0.64 
               
               
                 Lower limit of 95% CI 
                  0.0145 
                  0.0622 
                  0.304 
                  0.0157 
                  0.0728 
                  0.279 
                  0.0170 
                  0.0728 
                  0.421 
               
               
                 Upper limit of 95% CI 
                  0.937 
                  0.552 
                  3.29 
                  1.02 
                  0.638 
                  2.99 
                  1.11 
                  0.638 
                  4.14 
               
               
                 OR Quartile 3 
                  0.356 
                  0.144 
                  0.758 
                  0.400 
                  0.151 
                  0.667 
                  0.452 
                  0.151 
                  0.963 
               
               
                 p Value 
                  0.063 
                 1.5E−4 
                  0.60 
                  0.10 
                 1.6E−4 
                  0.44 
                  0.16 
                 1.6E−4 
                  0.94 
               
               
                 Lower limit of 95% CI 
                  0.120 
                  0.0530 
                  0.269 
                  0.133 
                  0.0563 
                  0.239 
                  0.149 
                  0.0563 
                  0.344 
               
               
                 Upper limit of 95% CI 
                  1.06 
                  0.393 
                  2.13 
                  1.20 
                  0.403 
                  1.86 
                  1.37 
                  0.403 
                  2.69 
               
               
                 OR Quartile 4 
                  0.455 
                  0.101 
                  1.00 
                  0.571 
                  0.150 
                  0.769 
                  0.735 
                  0.150 
                  1.44 
               
               
                 p Value 
                  0.17 
                  0.0036 
                  1.0 
                  0.34 
                  0.0050 
                  0.65 
                  0.61 
                  0.0050 
                  0.57 
               
               
                 Lower limit of 95% CI 
                  0.149 
                  0.0215 
                  0.304 
                  0.182 
                  0.0397 
                  0.244 
                  0.223 
                  0.0397 
                  0.410 
               
               
                 Upper limit of 95% CI 
                  1.39 
                  0.472 
                  3.29 
                  1.80 
                  0.564 
                  2.42 
                  2.42 
                  0.564 
                  5.03 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 24 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.90 
                  3.15 
                  5.79 
                  3.28 
                  5.79 
                  3.36 
               
               
                 Average 
                  6.37 
                  4.17 
                  6.20 
                  4.28 
                  5.83 
                  4.46 
               
               
                 Stdev 
                  3.54 
                  4.18 
                  3.52 
                  4.22 
                  3.11 
                  4.39 
               
               
                 p (t-test) 
                   
                  0.022 
                   
                  0.046 
                   
                  0.13 
               
               
                 Min 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 14.5 
                 20.6 
                 14.5 
                 20.6 
                 13.5 
                 20.6 
               
               
                 n (Patient) 
                 24 
                 56 
                 23 
                 57 
                 22 
                 58 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.58 
                  2.44 
                  5.54 
                  2.47 
                  5.58 
                  2.51 
               
               
                 Average 
                  6.41 
                  2.81 
                  6.32 
                  3.02 
                  6.34 
                  3.08 
               
               
                 Stdev 
                  4.49 
                  2.38 
                  4.50 
                  2.65 
                  4.55 
                  2.65 
               
               
                 p (t-test) 
                   
                 2.1E−5 
                   
                 1.4E−4 
                   
                 1.9E−4 
               
               
                 Min 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
                  0.502 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 45 
                 35 
                 44 
                 36 
                 43 
                 37 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.02 
                  3.84 
                  5.16 
                  3.67 
                  4.74 
                  4.01 
               
               
                 Average 
                  4.96 
                  4.82 
                  5.19 
                  4.77 
                  4.42 
                  5.09 
               
               
                 Stdev 
                  3.39 
                  4.38 
                  3.49 
                  4.42 
                  2.70 
                  4.61 
               
               
                 p (t-test) 
                   
                  0.89 
                   
                  0.67 
                   
                  0.46 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                 14.5 
                 20.6 
                 14.5 
                 20.6 
                 8.84 
                 20.6 
               
               
                 n (Patient) 
                 22 
                 46 
                 23 
                 45 
                 22 
                 47 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.28 
                  0.21 
                  0.45 
                  0.30 
                  0.24 
                  0.43 
                  0.33 
                  0.25 
                  0.49 
               
               
                 SE 
                  0.059 
                  0.053 
                  0.074 
                  0.061 
                  0.055 
                  0.072 
                  0.064 
                  0.055 
                  0.075 
               
               
                 p Value 
                 2.4E−4 
                 6.3E−8 
                 0.49 
                 0.0014 
                 1.4E−6 
                  0.31 
                  0.0071 
                 3.8E−6 
                  0.91 
               
               
                 nCohort Recovered 
                 24 
                 45 
                 22 
                 23 
                 44 
                 23 
                 22 
                 43 
                 22 
               
               
                 nCohort Non-recovered 
                 56 
                 35 
                 46 
                 57 
                 36 
                 45 
                 58 
                 37 
                 47 
               
               
                 Cutoff Quartile 2 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.90 
                  1.99 
               
               
                 Sensitivity 
                 66% 
                 57% 
                 74% 
                 67% 
                 58% 
                 73% 
                 67% 
                 59% 
                 74% 
               
               
                 Specificity 
                  4% 
                 11% 
                 23% 
                  4% 
                 11% 
                 22% 
                  5% 
                 12% 
                 27% 
               
               
                 Cutoff Quartile 3 
                  3.77 
                  3.77 
                  4.30 
                  3.77 
                  3.77 
                  4.30 
                  3.77 
                  3.77 
                  4.18 
               
               
                 Sensitivity 
                 41% 
                 23% 
                 46% 
                 42% 
                 25% 
                 44% 
                 43% 
                 27% 
                 47% 
               
               
                 Specificity 
                 29% 
                 29% 
                 41% 
                 30% 
                 30% 
                 39% 
                 32% 
                 30% 
                 45% 
               
               
                 Cutoff Quartile 4 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.30 
                  6.29 
               
               
                 Sensitivity 
                 16% 
                  6% 
                 22% 
                 18% 
                  8% 
                 20% 
                 19% 
                  8% 
                 23% 
               
               
                 Specificity 
                 54% 
                 60% 
                 68% 
                 57% 
                 61% 
                 65% 
                 59% 
                 60% 
                 73% 
               
               
                 OR Quartile 2 
                  0.0847 
                  0.167 
                  0.833 
                  0.0909 
                  0.179 
                  0.764 
                  0.0977 
                  0.193 
                  1.09 
               
               
                 p Value 
                  0.020 
                  0.0022 
                  0.76 
                  0.024 
                  0.0032 
                  0.66 
                  0.028 
                  0.0047 
                  0.88 
               
               
                 Lower limit of 95% CI 
                  0.0106 
                  0.0530 
                  0.252 
                  0.0114 
                  0.0572 
                  0.232 
                  0.0122 
                  0.0617 
                  0.348 
               
               
                 Upper limit of 95% CI 
                  0.676 
                  0.524 
                  2.75 
                  0.726 
                  0.563 
                  2.51 
                  0.782 
                  0.604 
                  3.44 
               
               
                 OR Quartile 3 
                  0.287 
                  0.120 
                  0.582 
                  0.318 
                  0.140 
                  0.514 
                  0.354 
                  0.160 
                  0.733 
               
               
                 p Value 
                  0.017 
                 4.6E−5 
                  0.30 
                  0.030 
                 1.0E−4 
                  0.20 
                  0.049 
                 2.3E−4 
                  0.55 
               
               
                 Lower limit of 95% CI 
                  0.103 
                  0.0435 
                  0.208 
                  0.113 
                  0.0517 
                  0.185 
                  0.125 
                  0.0606 
                  0.265 
               
               
                 Upper limit of 95% CI 
                  0.803 
                  0.333 
                  1.63 
                  0.893 
                  0.378 
                  1.43 
                  0.997 
                  0.425 
                  2.03 
               
               
                 OR Quartile 4 
                  0.226 
                  0.0909 
                  0.595 
                  0.277 
                  0.144 
                  0.469 
                  0.338 
                  0.135 
                  0.815 
               
               
                 p Value 
                  0.0067 
                  0.0024 
                  0.37 
                  0.019 
                  0.0043 
                  0.19 
                  0.048 
                  0.0031 
                  0.73 
               
               
                 Lower limit of 95% CI 
                  0.0773 
                  0.0194 
                  0.191 
                  0.0948 
                  0.0382 
                  0.152 
                  0.116 
                  0.0357 
                  0.256 
               
               
                 Upper limit of 95% CI 
                  0.662 
                  0.427 
                  1.86 
                  0.807 
                  0.545 
                  1.45 
                  0.989 
                  0.510 
                  2.59 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 48 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.67 
                  2.65 
                  5.67 
                  2.91 
                  5.58 
                  3.03 
               
               
                 Average 
                  6.19 
                  3.61 
                  5.96 
                  4.00 
                  5.88 
                  4.10 
               
               
                 Stdev 
                  4.10 
                  3.75 
                  3.96 
                  4.05 
                  3.99 
                  4.06 
               
               
                 p (t-test) 
                   
                  0.0051 
                   
                  0.036 
                   
                  0.059 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
               
               
                 Max 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
               
               
                 n (Patient) 
                 38 
                 42 
                 34 
                 46 
                 33 
                 47 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.36 
                  2.65 
                  5.32 
                  2.78 
                  5.32 
                  2.78 
               
               
                 Average 
                  6.01 
                  3.20 
                  6.03 
                  3.27 
                  6.03 
                  3.27 
               
               
                 Stdev 
                  4.52 
                  2.75 
                  4.57 
                  2.73 
                  4.57 
                  2.73 
               
               
                 p (t-test) 
                   
                  0.0011 
                   
                  0.0014 
                   
                  0.0014 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 47 
                 32 
                 46 
                 33 
                 46 
                 33 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.16 
                  2.91 
                  4.88 
                  3.28 
                  4.67 
                  3.36 
               
               
                 Average 
                  5.49 
                  3.87 
                  4.76 
                  4.54 
                  4.59 
                  4.66 
               
               
                 Stdev 
                  3.43 
                  4.07 
                  2.79 
                  4.42 
                  2.72 
                  4.42 
               
               
                 p (t-test) 
                   
                  0.11 
                   
                  0.81 
                   
                  0.95 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                 14.5 
                 20.5 
                 9.65 
                 20.5 
                 9.65 
                 20.5 
               
               
                 n (Patient) 
                 29 
                 30 
                 25 
                 35 
                 24 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.27 
                  0.28 
                  0.32 
                  0.30 
                  0.29 
                  0.41 
                  0.32 
                  0.29 
                  0.44 
               
               
                 SE 
                  0.056 
                  0.060 
                  0.070 
                  0.058 
                  0.060 
                  0.074 
                  0.059 
                  0.060 
                  0.075 
               
               
                 p Value 
                 2.3E−5 
                 2.7E−4 
                  0.0095 
                 7.0E−4 
                 5.3E−4 
                  0.23 
                  0.0023 
                 5.3E−4 
                  0.39 
               
               
                 nCohort Recovered 
                 38 
                 47 
                 29 
                 34 
                 46 
                 25 
                 33 
                 46 
                 21 
               
               
                 nCohort Non-recovered 
                 42 
                 32 
                 30 
                 46 
                 33 
                 35 
                 47 
                 33 
                 36 
               
               
                 Cutoff Quartile 2 
                  1.90 
                  2.05 
                  1.62 
                  1.90 
                  2.05 
                  1.63 
                  1.90 
                  2.05 
                  1.63 
               
               
                 Sensitivity 
                 60% 
                 62% 
                 60% 
                 63% 
                 64% 
                 66% 
                 64% 
                 64% 
                 67% 
               
               
                 Specificity 
                  8% 
                 17% 
                 10% 
                  9% 
                 17% 
                 12% 
                  9% 
                 17% 
                 12% 
               
               
                 Cutoff Quartile 3 
                  3.77 
                  3.81 
                  3.81 
                  3.77 
                  3.81 
                  3.77 
                  3.77 
                  3.81 
                  3.77 
               
               
                 Sensitivity 
                 33% 
                 28% 
                 37% 
                 37% 
                 30% 
                 43% 
                 38% 
                 30% 
                 44% 
               
               
                 Specificity 
                 32% 
                 36% 
                 38% 
                 32% 
                 37% 
                 40% 
                 33% 
                 37% 
                 42% 
               
               
                 Cutoff Quartile 4 
                  6.30 
                  6.30 
                  6.15 
                  6.30 
                  6.30 
                  6.08 
                  6.30 
                  6.30 
                  6.08 
               
               
                 Sensitivity 
                 12% 
                  9% 
                 17% 
                 15% 
                  9% 
                 23% 
                 17% 
                  9% 
                 25% 
               
               
                 Specificity 
                 61% 
                 64% 
                 66% 
                 62% 
                 63% 
                 72% 
                 64% 
                 63% 
                 75% 
               
               
                 OR Quartile 2 
                  0.126 
                  0.342 
                  0.173 
                  0.165 
                  0.368 
                  0.261 
                  0.176 
                  0.368 
                  0.286 
               
               
                 p Value 
                  0.0023 
                  0.044 
                  0.014 
                  0.0078 
                  0.060 
                  0.059 
                  0.010 
                  0.060 
                  0.078 
               
               
                 Lower limit of 95% CI 
                  0.0333 
                  0.120 
                  0.0427 
                  0.0438 
                  0.130 
                  0.0649 
                  0.0468 
                  0.130 
                  0.0709 
               
               
                 Upper limit of 95% CI 
                  0.477 
                  0.972 
                  0.702 
                  0.623 
                  1.04 
                  1.05 
                  0.666 
                  1.04 
                  1.15 
               
               
                 OR Quartile 3 
                  0.231 
                  0.222 
                  0.354 
                  0.280 
                  0.255 
                  0.500 
                  0.310 
                  0.255 
                  0.571 
               
               
                 p Value 
                  0.0022 
                  0.0024 
                  0.054 
                  0.0077 
                  0.0050 
                  0.19 
                  0.014 
                  0.0050 
                  0.29 
               
               
                 Lower limit of 95% CI 
                  0.0903 
                  0.0838 
                  0.123 
                  0.110 
                  0.0982 
                  0.176 
                  0.122 
                  0.0982 
                  0.201 
               
               
                 Upper limit of 95% CI 
                  0.589 
                  0.587 
                  1.02 
                  0.714 
                  0.661 
                  1.42 
                  0.789 
                  0.661 
                  1.62 
               
               
                 OR Quartile 4 
                  0.207 
                  0.183 
                  0.380 
                  0.290 
                  0.171 
                  0.762 
                  0.359 
                  0.171 
                  1.00 
               
               
                 p Value 
                  0.0067 
                  0.012 
                  0.12 
                  0.022 
                  0.0091 
                  0.65 
                  0.054 
                  0.0091 
                  1.0 
               
               
                 Lower limit of 95% CI 
                  0.0664 
                  0.0483 
                  0.111 
                  0.100 
                  0.0451 
                  0.235 
                  0.127 
                  0.0451 
                  0.303 
               
               
                 Upper limit of 95% CI 
                  0.647 
                  0.690 
                  1.30 
                  0.838 
                  0.645 
                  2.47 
                  1.02 
                  0.645 
                  3.30 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 72 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.54 
                  2.44 
                  5.49 
                  2.47 
                  5.49 
                  2.47 
               
               
                 Average 
                  5.89 
                  3.47 
                  5.81 
                  3.60 
                  5.81 
                  3.60 
               
               
                 Stdev 
                  3.78 
                  3.32 
                  3.79 
                  3.38 
                  3.79 
                  3.38 
               
               
                 p (t-test) 
                   
                  0.0039 
                   
                  0.0090 
                   
                  0.0090 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
               
               
                 Max 
                 20.5 
                 14.5 
                 20.5 
                 14.5 
                 20.5 
                 14.5 
               
               
                 n (Patient) 
                 38 
                 41 
                 37 
                 42 
                 37 
                 42 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.02 
                  2.51 
                  5.02 
                  2.51 
                  5.02 
                  2.51 
               
               
                 Average 
                  5.72 
                  3.21 
                  5.72 
                  3.21 
                  5.72 
                  3.21 
               
               
                 Stdev 
                  3.98 
                  2.80 
                  3.98 
                  2.80 
                  3.98 
                  2.80 
               
               
                 p (t-test) 
                   
                  0.0020 
                   
                  0.0020 
                   
                  0.0020 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
               
               
                 Max 
                 20.5 
                 11.5 
                 20.5 
                 11.5 
                 20.5 
                 11.5 
               
               
                 n (Patient) 
                 46 
                 31 
                 46 
                 31 
                 46 
                 31 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.09 
                  2.91 
                  3.72 
                  3.03 
                  3.72 
                  3.03 
               
               
                 Average 
                  4.28 
                  3.92 
                  4.04 
                  4.06 
                  4.04 
                  4.06 
               
               
                 Stdev 
                  2.74 
                  3.56 
                  2.59 
                  3.60 
                  2.59 
                  3.60 
               
               
                 p (t-test) 
                   
                  0.69 
                   
                  0.98 
                   
                  0.98 
               
               
                 Min 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                  9.53 
                 14.5 
                  9.53 
                 14.5 
                  9.53 
                 14.5 
               
               
                 n (Patient) 
                 20 
                 32 
                 19 
                 33 
                 19 
                 33 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.27 
                  0.28 
                  0.42 
                  0.29 
                  0.28 
                  0.45 
                  0.29 
                  0.28 
                  0.45 
               
               
                 SE 
                  0.056 
                  0.061 
                  0.081 
                  0.057 
                  0.061 
                  0.083 
                  0.057 
                  0.061 
                  0.083 
               
               
                 p Value 
                 3.8E−5 
                 4.3E−4 
                  0.32 
                 1.9E−4 
                 4.3E−4 
                  0.54 
                 1.9E−4 
                 4.3E−4 
                  0.54 
               
               
                 nCohort Recovered 
                 38 
                 46 
                 20 
                 37 
                 46 
                 19 
                 37 
                 46 
                 19 
               
               
                 nCohort Non-recovered 
                 41 
                 31 
                 32 
                 42 
                 31 
                 33 
                 42 
                 31 
                 33 
               
               
                 Cutoff Quartile 2 
                  1.81 
                  2.12 
                  1.56 
                  1.81 
                  2.12 
                  1.56 
                  1.81 
                  2.12 
                  1.56 
               
               
                 Sensitivity 
                 59% 
                 61% 
                 69% 
                 60% 
                 61% 
                 70% 
                 60% 
                 61% 
                 70% 
               
               
                 Specificity 
                  8% 
                 17% 
                 15% 
                  8% 
                 17% 
                 16% 
                  8% 
                 17% 
                 16% 
               
               
                 Cutoff Quartile 3 
                  3.72 
                  3.81 
                  3.36 
                  3.72 
                  3.81 
                  3.36 
                  3.72 
                  3.81 
                  3.36 
               
               
                 Sensitivity 
                 32% 
                 29% 
                 44% 
                 33% 
                 29% 
                 45% 
                 33% 
                 29% 
                 45% 
               
               
                 Specificity 
                 32% 
                 37% 
                 40% 
                 32% 
                 37% 
                 42% 
                 32% 
                 37% 
                 42% 
               
               
                 Cutoff Quartile 4 
                  6.15 
                  6.29 
                  5.39 
                  6.15 
                  6.29 
                  5.39 
                  6.15 
                  6.29 
                  5.39 
               
               
                 Sensitivity 
                 15% 
                 10% 
                 19% 
                 17% 
                 10% 
                 21% 
                 17% 
                 10% 
                 21% 
               
               
                 Specificity 
                 63% 
                 65% 
                 65% 
                 65% 
                 65% 
                 68% 
                 65% 
                 65% 
                 68% 
               
               
                 OR Quartile 2 
                  0.121 
                  0.333 
                  0.388 
                  0.130 
                  0.333 
                  0.431 
                  0.130 
                  0.333 
                  0.431 
               
               
                 p Value 
                  0.0019 
                  0.040 
                  0.20 
                  0.0026 
                  0.040 
                  0.25 
                  0.0026 
                  0.040 
                  0.25 
               
               
                 Lower limit of 95% CI 
                  0.0319 
                  0.117 
                  0.0922 
                  0.0343 
                  0.117 
                  0.102 
                  0.0343 
                  0.117 
                  0.102 
               
               
                 Upper limit of 95% CI 
                  0.459 
                  0.953 
                  1.63 
                  0.491 
                  0.953 
                  1.82 
                  0.491 
                  0.953 
                  1.82 
               
               
                 OR Quartile 3 
                  0.214 
                  0.240 
                  0.519 
                  0.240 
                  0.240 
                  0.606 
                  0.240 
                  0.240 
                  0.606 
               
               
                 p Value 
                  0.0015 
                  0.0043 
                  0.26 
                  0.0030 
                  0.0043 
                  0.39 
                  0.0030 
                  0.0043 
                  0.39 
               
               
                 Lower limit of 95% CI 
                  0.0830 
                  0.0900 
                  0.167 
                  0.0937 
                  0.0900 
                  0.194 
                  0.0937 
                  0.0900 
                  0.194 
               
               
                 Upper limit of 95% CI 
                  0.554 
                  0.639 
                  1.61 
                  0.615 
                  0.639 
                  1.89 
                  0.615 
                  0.639 
                  1.89 
               
               
                 OR Quartile 4 
                  0.294 
                  0.201 
                  0.429 
                  0.369 
                  0.201 
                  0.583 
                  0.369 
                  0.201 
                  0.583 
               
               
                 p Value 
                  0.027 
                  0.019 
                  0.19 
                  0.064 
                  0.019 
                  0.41 
                  0.064 
                  0.019 
                  0.41 
               
               
                 Lower limit of 95% CI 
                  0.0990 
                  0.0528 
                  0.119 
                  0.128 
                  0.0528 
                  0.163 
                  0.128 
                  0.0528 
                  0.163 
               
               
                 Upper limit of 95% CI 
                  0.873 
                  0.764 
                  1.54 
                  1.06 
                  0.764 
                  2.09 
                  1.06 
                  0.764 
                  2.09 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts within 7 days after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.16 
                  2.35 
                  5.54 
                  2.51 
                  5.54 
                  2.51 
               
               
                 Average 
                  6.00 
                  3.11 
                  6.18 
                  3.11 
                  6.18 
                  3.11 
               
               
                 Stdev 
                  4.39 
                  2.63 
                  4.45 
                  2.55 
                  4.45 
                  2.55 
               
               
                 p (t-test) 
                   
                 3.8E−4 
                   
                 1.9E−4 
                   
                 1.9E−4 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 51 
                 32 
                 48 
                 35 
                 48 
                 35 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.87 
                  2.44 
                  4.88 
                  2.44 
                  4.88 
                  2.44 
               
               
                 Average 
                  5.57 
                  3.02 
                  5.66 
                  3.01 
                  5.66 
                  3.01 
               
               
                 Stdev 
                  4.33 
                  2.71 
                  4.37 
                  2.63 
                  4.37 
                  2.63 
               
               
                 p (t-test) 
                   
                  0.0027 
                   
                  0.0014 
                   
                  0.0014 
               
               
                 Min 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
                  0.366 
                  0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 58 
                 23 
                 56 
                 25 
                 56 
                 25 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.02 
                  3.28 
                  5.16 
                  3.23 
                  5.02 
                  3.43 
               
               
                 Average 
                  5.61 
                  4.41 
                  5.69 
                  4.29 
                  5.56 
                  4.46 
               
               
                 Stdev 
                  3.99 
                  4.15 
                  4.02 
                  4.08 
                  4.01 
                  4.14 
               
               
                 p (t-test) 
                   
                  0.20 
                   
                  0.14 
                   
                  0.24 
               
               
                 Min 
                  0.0344 
                  0.398 
                  0.366 
                  0.398 
                  0.366 
                  0.398 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 40 
                 39 
                 41 
                 38 
                 40 
                 39 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.27 
                  0.29 
                  0.38 
                  0.26 
                  0.29 
                  0.36 
                  0.26 
                  0.29 
                  0.39 
               
               
                 SE 
                  0.059 
                  0.068 
                  0.063 
                  0.057 
                  0.065 
                  0.063 
                  0.057 
                  0.065 
                  0.063 
               
               
                 p Value 
                 8.5E−5 
                  0.0020 
                  0.050 
                 1.9E−5 
                 9.8E−4 
                  0.029 
                 1.9E−5 
                 9.8E−4 
                  0.073 
               
               
                 nCohort Recovered 
                 51 
                 58 
                 40 
                 48 
                 56 
                 41 
                 48 
                 56 
                 40 
               
               
                 nCohort Non-recovered 
                 32 
                 23 
                 39 
                 35 
                 25 
                 38 
                 35 
                 25 
                 39 
               
               
                 Cutoff Quartile 2 
                  2.05 
                  1.99 
                  2.05 
                  2.05 
                  1.99 
                  2.05 
                  2.05 
                  1.99 
                  2.05 
               
               
                 Sensitivity 
                 56% 
                 61% 
                 67% 
                 57% 
                 60% 
                 66% 
                 57% 
                 60% 
                 67% 
               
               
                 Specificity 
                 14% 
                 21% 
                 18% 
                 12% 
                 20% 
                 17% 
                 12% 
                 20% 
                 18% 
               
               
                 Cutoff Quartile 3 
                  4.01 
                  3.81 
                  4.42 
                  4.01 
                  3.81 
                  4.42 
                  4.01 
                  3.81 
                  4.42 
               
               
                 Sensitivity 
                 28% 
                 22% 
                 36% 
                 29% 
                 24% 
                 37% 
                 29% 
                 24% 
                 38% 
               
               
                 Specificity 
                 37% 
                 40% 
                 38% 
                 35% 
                 39% 
                 39% 
                 35% 
                 39% 
                 40% 
               
               
                 Cutoff Quartile 4 
                  6.30 
                  6.29 
                  6.35 
                  6.30 
                  6.29 
                  6.35 
                  6.30 
                  6.29 
                  6.35 
               
               
                 Sensitivity 
                  9% 
                  9% 
                 18% 
                  9% 
                  8% 
                 16% 
                  9% 
                  8% 
                 18% 
               
               
                 Specificity 
                 65% 
                 69% 
                 68% 
                 62% 
                 68% 
                 66% 
                 62% 
                 68% 
                 68% 
               
               
                 OR Quartile 2 
                  0.205 
                  0.406 
                  0.424 
                  0.190 
                  0.367 
                  0.396 
                  0.190 
                  0.367 
                  0.424 
               
               
                 p Value 
                  0.0033 
                  0.093 
                  0.11 
                  0.0028 
                  0.058 
                  0.085 
                  0.0028 
                  0.058 
                  0.11 
               
               
                 Lower limit of 95% CI 
                  0.0709 
                  0.142 
                  0.148 
                  0.0643 
                  0.130 
                  0.138 
                  0.0643 
                  0.130 
                  0.148 
               
               
                 Upper limit of 95% CI 
                  0.590 
                  1.16 
                  1.22 
                  0.564 
                  1.03 
                  1.14 
                  0.564 
                  1.03 
                  1.22 
               
               
                 OR Quartile 3 
                  0.232 
                  0.183 
                  0.336 
                  0.219 
                  0.204 
                  0.373 
                  0.219 
                  0.204 
                  0.417 
               
               
                 p Value 
                  0.0028 
                  0.0030 
                  0.020 
                  0.0016 
                  0.0034 
                  0.034 
                  0.0016 
                  0.0034 
                  0.058 
               
               
                 Lower limit of 95% CI 
                  0.0892 
                  0.0594 
                  0.135 
                  0.0855 
                  0.0706 
                  0.150 
                  0.0855 
                  0.0706 
                  0.169 
               
               
                 Upper limit of 95% CI 
                  0.605 
                  0.560 
                  0.839 
                  0.563 
                  0.592 
                  0.928 
                  0.563 
                  0.592 
                  1.03 
               
               
                 OR Quartile 4 
                  0.190 
                  0.212 
                  0.454 
                  0.156 
                  0.184 
                  0.362 
                  0.156 
                  0.184 
                  0.454 
               
               
                 p Value 
                  0.014 
                  0.050 
                  0.14 
                  0.0058 
                  0.032 
                  0.066 
                  0.0058 
                  0.032 
                  0.14 
               
               
                 Lower limit of 95% CI 
                  0.0507 
                  0.0448 
                  0.159 
                  0.0417 
                  0.0390 
                  0.122 
                  0.0417 
                  0.0390 
                  0.159 
               
               
                 Upper limit of 95% CI 
                  0.710 
                  1.00 
                  1.30 
                  0.585 
                  0.865 
                  1.07 
                  0.585 
                  0.865 
                  1.30 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 12 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.659 
                  0.584 
                  0.682 
                  0.575 
                  0.718 
                  0.584 
               
               
                 Average 
                  0.828 
                  0.881 
                  0.843 
                  0.875 
                  0.855 
                  0.871 
               
               
                 Stdev 
                  0.681 
                  0.886 
                  0.695 
                  0.880 
                  0.712 
                  0.874 
               
               
                 p (t-test) 
                   
                  0.78 
                   
                  0.87 
                   
                  0.94 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 20 
                 62 
                 19 
                 63 
                 18 
                 64 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.527 
                  0.979 
                  0.539 
                  0.738 
                  0.539 
                  0.738 
               
               
                 Average 
                  0.724 
                  1.07 
                  0.734 
                  1.04 
                  0.734 
                  1.04 
               
               
                 Stdev 
                  0.611 
                  1.04 
                  0.623 
                  1.02 
                  0.623 
                  1.02 
               
               
                 p (t-test) 
                   
                  0.087 
                   
                  0.12 
                   
                  0.12 
               
               
                 Min 
                  0.108 
                  0.204 
                  0.108 
                  0.204 
                  0.108 
                  0.204 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 46 
                 35 
                 44 
                 37 
                 44 
                 37 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.682 
                  0.571 
                  0.659 
                  0.567 
                  0.682 
                  0.567 
               
               
                 Average 
                  1.01 
                  0.814 
                  0.988 
                  0.815 
                  0.989 
                  0.806 
               
               
                 Stdev 
                  1.06 
                  0.771 
                  1.04 
                  0.778 
                  1.07 
                  0.764 
               
               
                 p (t-test) 
                   
                  0.46 
                   
                  0.50 
                   
                  0.49 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 21 
                 50 
                 22 
                 49 
                 21 
                 51 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.50 
                  0.63 
                  0.45 
                  0.50 
                  0.62 
                  0.45 
                  0.50 
                  0.62 
                  0.47 
               
               
                 SE 
                  0.075 
                  0.063 
                  0.074 
                  0.076 
                  0.063 
                  0.073 
                  0.077 
                  0.063 
                  0.074 
               
               
                 p Value 
                  0.97 
                  0.045 
                  0.46 
                  1.00 
                  0.063 
                  0.48 
                  1.0 
                  0.063 
                  0.66 
               
               
                 nCohort Recovered 
                 20 
                 46 
                 21 
                 19 
                 44 
                 22 
                 18 
                 44 
                 21 
               
               
                 nCohort Non-recovered 
                 62 
                 35 
                 50 
                 63 
                 37 
                 49 
                 64 
                 37 
                 51 
               
               
                 Cutoff Quartile 2 
                  0.374 
                  0.374 
                  0.375 
                  0.374 
                  0.374 
                  0.375 
                  0.374 
                  0.374 
                  0.374 
               
               
                 Sensitivity 
                 76% 
                 80% 
                 76% 
                 76% 
                 81% 
                 76% 
                 77% 
                 81% 
                 76% 
               
               
                 Specificity 
                 30% 
                 30% 
                 29% 
                 32% 
                 32% 
                 27% 
                 33% 
                 32% 
                 29% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.636 
                  0.636 
                  0.614 
                  0.636 
                  0.593 
                  0.614 
                  0.636 
                  0.584 
               
               
                 Sensitivity 
                 48% 
                 60% 
                 48% 
                 48% 
                 57% 
                 47% 
                 48% 
                 57% 
                 47% 
               
               
                 Specificity 
                 45% 
                 59% 
                 48% 
                 42% 
                 57% 
                 45% 
                 44% 
                 57% 
                 43% 
               
               
                 Cutoff Quartile 4 
                  1.04 
                  1.04 
                  0.990 
                  1.04 
                  1.04 
                  0.990 
                  1.04 
                  1.04 
                  0.984 
               
               
                 Sensitivity 
                 26% 
                 40% 
                 24% 
                 25% 
                 38% 
                 24% 
                 25% 
                 38% 
                 24% 
               
               
                 Specificity 
                 75% 
                 87% 
                 71% 
                 74% 
                 86% 
                 73% 
                 72% 
                 86% 
                 71% 
               
               
                 OR Quartile 2 
                  1.34 
                  1.75 
                  1.27 
                  1.48 
                  2.00 
                  1.16 
                  1.63 
                  2.00 
                  1.30 
               
               
                 p Value 
                  0.61 
                  0.29 
                  0.69 
                  0.50 
                  0.19 
                  0.80 
                  0.40 
                  0.19 
                  0.65 
               
               
                 Lower limit of 95% CI 
                  0.439 
                  0.619 
                  0.402 
                  0.478 
                  0.708 
                  0.369 
                  0.523 
                  0.708 
                  0.413 
               
               
                 Upper limit of 95% CI 
                  4.11 
                  4.95 
                  3.99 
                  4.56 
                  5.65 
                  3.62 
                  5.10 
                  5.65 
                  4.09 
               
               
                 OR Quartile 3 
                  0.767 
                  2.13 
                  0.839 
                  0.661 
                  1.73 
                  0.737 
                  0.752 
                  1.73 
                  0.667 
               
               
                 p Value 
                  0.61 
                  0.098 
                  0.74 
                  0.43 
                  0.22 
                  0.55 
                  0.59 
                  0.22 
                  0.44 
               
               
                 Lower limit of 95% CI 
                  0.279 
                  0.871 
                  0.302 
                  0.235 
                  0.714 
                  0.269 
                  0.263 
                  0.714 
                  0.239 
               
               
                 Upper limit of 95% CI 
                  2.11 
                  5.22 
                  2.33 
                  1.86 
                  4.17 
                  2.02 
                  2.15 
                  4.17 
                  1.86 
               
               
                 OR Quartile 4 
                  1.04 
                  4.44 
                  0.789 
                  0.953 
                  3.86 
                  0.865 
                  0.867 
                  3.86 
                  0.769 
               
               
                 p Value 
                  0.94 
                  0.0075 
                  0.69 
                  0.94 
                  0.015 
                  0.80 
                  0.81 
                  0.015 
                  0.65 
               
               
                 Lower limit of 95% CI 
                  0.327 
                  1.49 
                  0.251 
                  0.296 
                  1.30 
                  0.276 
                  0.267 
                  1.30 
                  0.244 
               
               
                 Upper limit of 95% CI 
                  3.33 
                 13.3 
                  2.49 
                  3.07 
                 11.4 
                  2.71 
                  2.81 
                 11.4 
                  2.42 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 24 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.602 
                  0.618 
                  0.636 
                  0.593 
                  0.625 
                  0.614 
               
               
                 Average 
                  0.763 
                  0.924 
                  0.795 
                  0.903 
                  0.802 
                  0.899 
               
               
                 Stdev 
                  0.616 
                  0.936 
                  0.647 
                  0.916 
                  0.660 
                  0.908 
               
               
                 p (t-test) 
                   
                  0.37 
                   
                  0.56 
                   
                  0.61 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 26 
                 54 
                 23 
                 57 
                 22 
                 58 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.544 
                  0.738 
                  0.555 
                  0.691 
                  0.561 
                  0.644 
               
               
                 Average 
                  0.736 
                  1.08 
                  0.741 
                  1.06 
                  0.754 
                  1.04 
               
               
                 Stdev 
                  0.614 
                  1.07 
                  0.620 
                  1.06 
                  0.621 
                  1.05 
               
               
                 p (t-test) 
                   
                  0.11 
                   
                  0.12 
                   
                  0.17 
               
               
                 Min 
                  0.108 
                  0.217 
                  0.108 
                  0.217 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 46 
                 33 
                 45 
                 34 
                 44 
                 35 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.656 
                  0.609 
                  0.659 
                  0.575 
                  0.682 
                  0.575 
               
               
                 Average 
                  0.950 
                  0.848 
                  0.969 
                  0.835 
                  0.969 
                  0.825 
               
               
                 Stdev 
                  0.981 
                  0.813 
                  0.996 
                  0.807 
                  1.02 
                  0.791 
               
               
                 p (t-test) 
                   
                  0.67 
                   
                  0.58 
                   
                  0.56 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 25 
                 44 
                 24 
                 45 
                 23 
                 47 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.53 
                  0.61 
                  0.46 
                  0.52 
                  0.61 
                  0.44 
                  0.52 
                  0.59 
                  0.46 
               
               
                 SE 
                  0.069 
                  0.065 
                  0.072 
                  0.071 
                  0.065 
                  0.072 
                  0.072 
                  0.065 
                  0.073 
               
               
                 p Value 
                  0.66 
                  0.078 
                  0.58 
                  0.83 
                  0.088 
                  0.43 
                  0.82 
                  0.19 
                  0.57 
               
               
                 nCohort Recovered 
                 26 
                 46 
                 25 
                 23 
                 45 
                 24 
                 22 
                 44 
                 23 
               
               
                 nCohort Non-recovered 
                 54 
                 33 
                 44 
                 57 
                 34 
                 45 
                 58 
                 35 
                 47 
               
               
                 Cutoff Quartile 2 
                  0.374 
                  0.375 
                  0.376 
                  0.374 
                  0.375 
                  0.376 
                  0374 
                  0.375 
                  0.375 
               
               
                 Sensitivity 
                 78% 
                 82% 
                 75% 
                 77% 
                 82% 
                 73% 
                 78% 
                 80% 
                 77% 
               
               
                 Specificity 
                 31% 
                 30% 
                 28% 
                 30% 
                 31% 
                 25% 
                 32% 
                 30% 
                 30% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.636 
                  0.643 
                  0.614 
                  0.636 
                  0.636 
                  0.614 
                  0.636 
                  0.614 
               
               
                 Sensitivity 
                 50% 
                 58% 
                 48% 
                 49% 
                 56% 
                 49% 
                 50% 
                 54% 
                 49% 
               
               
                 Specificity 
                 50% 
                 57% 
                 48% 
                 48% 
                 56% 
                 50% 
                 50% 
                 55% 
                 48% 
               
               
                 Cutoff Quartile 4 
                  1.04 
                  1.04 
                  1.00 
                  1.04 
                  1.04 
                  1.00 
                  1.04 
                  1.04 
                  0.995 
               
               
                 Sensitivity 
                 28% 
                 36% 
                 25% 
                 26% 
                 35% 
                 24% 
                 26% 
                 34% 
                 26% 
               
               
                 Specificity 
                 81% 
                 83% 
                 76% 
                 78% 
                 82% 
                 75% 
                 77% 
                 82% 
                 74% 
               
               
                 OR Quartile 2 
                  1.56 
                  1.97 
                  1.17 
                  1.48 
                  2.11 
                  0.917 
                  1.62 
                  1.68 
                  1.43 
               
               
                 p Value 
                  0.41 
                  0.22 
                  0.79 
                  0.48 
                  0.18 
                  0.88 
                  0.39 
                  0.33 
                  0.53 
               
               
                 Lower limit of 95% CI 
                  0.544 
                  0.665 
                  0.385 
                  0.502 
                  0.713 
                  0.294 
                  0.544 
                  0.586 
                  0.469 
               
               
                 Upper limit of 95% CI 
                  4.45 
                  5.83 
                  3.53 
                  4.37 
                  6.23 
                  2.85 
                  4.80 
                  4.80 
                  4.37 
               
               
                 OR Quartile 3 
                  1.00 
                  1.76 
                  0.843 
                  0.885 
                  1.58 
                  0.957 
                  1.00 
                  1.42 
                  0.878 
               
               
                 p Value 
                  1.0 
                  0.22 
                  0.73 
                  0.80 
                  0.32 
                  0.93 
                  1.0 
                  0.44 
                  0.80 
               
               
                 Lower limit of 95% CI 
                  0.392 
                  0.715 
                  0.315 
                  0.336 
                  0.646 
                  0.355 
                  0.375 
                  0.584 
                  0.324 
               
               
                 Upper limit of 95% CI 
                  2.55 
                  4.35 
                  2.25 
                  2.33 
                  3.88 
                  2.58 
                  2.67 
                  3.47 
                  2.38 
               
               
                 OR Quartile 4 
                  1.62 
                  2.71 
                  1.06 
                  1.29 
                  2.52 
                  0.971 
                  1.19 
                  2.35 
                  0.971 
               
               
                 p Value 
                  0.41 
                  0.060 
                  0.93 
                  0.67 
                  0.081 
                  0.96 
                  0.77 
                  0.11 
                  0.96 
               
               
                 Lower limit of 95% CI 
                  0.515 
                  0.958 
                  0.336 
                  0.406 
                  0.893 
                  0.308 
                  0.373 
                  0.833 
                  0.311 
               
               
                 Upper limit of 95% CI 
                  5.06 
                  7.69 
                  3.31 
                  4.07 
                  7.13 
                  3.06 
                  3.77 
                  6.62 
                  3.03 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 48 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.539 
                  0.644 
                  0.561 
                  0.636 
                  0.567 
                  0.614 
               
               
                 Average 
                  0.668 
                  1.02 
                  0.698 
                  0.966 
                  0.710 
                  0.952 
               
               
                 Stdev 
                  0.511 
                  1.03 
                  0.531 
                  0.997 
                  0.536 
                  0.990 
               
               
                 p (t-test) 
                   
                  0.062 
                   
                  0.14 
                   
                  0.17 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 36 
                 41 
                 32 
                 45 
                 31 
                 46 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.503 
                  0.691 
                  0.522 
                  0.644 
                  0.522 
                  0.644 
               
               
                 Average 
                  0.706 
                  1.09 
                  0.718 
                  1.06 
                  0.718 
                  1.06 
               
               
                 Stdev 
                  0.594 
                  1.10 
                  0.595 
                  1.09 
                  0.595 
                  1.09 
               
               
                 p (t-test) 
                   
                  0.096 
                   
                  0.13 
                   
                  0.13 
               
               
                 Min 
                  0.108 
                  0.217 
                  0.108 
                  0172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
                  2.99 
                  4.86 
               
               
                 n (Patient) 
                 46 
                 30 
                 45 
                 31 
                 45 
                 31 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.593 
                  0.644 
                  0.682 
                  0.575 
                  0.718 
                  0.553 
               
               
                 Average 
                  0.771 
                  0.963 
                  0.816 
                  0.890 
                  0.838 
                  0.875 
               
               
                 Stdev 
                  0.561 
                  0.946 
                  0.596 
                  0.896 
                  0.600 
                  0.888 
               
               
                 p (t-test) 
                   
                  0.36 
                   
                  0.71 
                   
                  0.85 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  2.99 
                  4.60 
                  2.99 
                  4.60 
                  2.99 
                  4.60 
               
               
                 n (Patient) 
                 27 
                 30 
                 23 
                 35 
                 22 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.60 
                  0.64 
                  0.50 
                  0.56 
                  0.61 
                  0.46 
                  0.55 
                  0.61 
                  0.44 
               
               
                 SE 
                  0.065 
                  0.066 
                  0.077 
                  0.066 
                  0.067 
                  0.077 
                  0.067 
                  0.067 
                  0.077 
               
               
                 p Value 
                  0.13 
                  0.034 
                  0.97 
                  0.34 
                  0.090 
                  0.59 
                  0.49 
                  0.090 
                  0.40 
               
               
                 nCohort Recovered 
                 36 
                 46 
                 27 
                 32 
                 45 
                 23 
                 31 
                 45 
                 22 
               
               
                 nCohort Non-recovered 
                 41 
                 30 
                 30 
                 45 
                 31 
                 35 
                 46 
                 31 
                 36 
               
               
                 Cutoff Quartile 2 
                  0.374 
                  0.374 
                  0.389 
                  0.374 
                  0.374 
                  0.379 
                  0.374 
                  0.374 
                  0.379 
               
               
                 Sensitivity 
                 78% 
                 90% 
                 67% 
                 78% 
                 87% 
                 71% 
                 76% 
                 87% 
                 69% 
               
               
                 Specificity 
                 31% 
                 35% 
                 19% 
                 31% 
                 33% 
                 22% 
                 29% 
                 33% 
                 18% 
               
               
                 Cutoff Quartile 3 
                  0.593 
                  0.584 
                  0.636 
                  0.593 
                  0.584 
                  0.614 
                  0.593 
                  0.584 
                  0.614 
               
               
                 Sensitivity 
                 54% 
                 60% 
                 53% 
                 51% 
                 58% 
                 49% 
                 50% 
                 58% 
                 47% 
               
               
                 Specificity 
                 56% 
                 57% 
                 56% 
                 53% 
                 56% 
                 48% 
                 52% 
                 56% 
                 45% 
               
               
                 Cutoff Quartile 4 
                  1.00 
                  1.01 
                  1.07 
                  1.00 
                  1.01 
                  1.06 
                  1.00 
                  1.01 
                  1.06 
               
               
                 Sensitivity 
                 34% 
                 37% 
                 27% 
                 31% 
                 35% 
                 26% 
                 30% 
                 35% 
                 25% 
               
               
                 Specificity 
                 86% 
                 83% 
                 78% 
                 84% 
                 82% 
                 74% 
                 84% 
                 82% 
                 73% 
               
               
                 OR Quartile 2 
                  1.56 
                  4.80 
                  0.455 
                  1.59 
                  3.38 
                  0.694 
                  1.30 
                  3.38 
                  0.505 
               
               
                 p Value 
                  0.39 
                  0.022 
                  0.21 
                  0.38 
                  0.051 
                  0.56 
                  0.62 
                  0.051 
                  0.30 
               
               
                 Lower limit of 95% CI 
                  0.562 
                  1.26 
                  0.133 
                  0.570 
                  0.997 
                  0.202 
                  0.465 
                  0.997 
                  0.138 
               
               
                 Upper limit of 95% CI 
                  4.36 
                 18.3 
                  1.56 
                  4.44 
                 11.4 
                  2.38 
                  3.65 
                 11.4 
                  1.84 
               
               
                 OR Quartile 3 
                  1.45 
                  1.95 
                  1.43 
                  1.18 
                  1.73 
                  0.866 
                  1.07 
                  1.73 
                  0.746 
               
               
                 p Value 
                  0.42 
                  0.16 
                  0.50 
                  0.71 
                  0.24 
                  0.79 
                  0.89 
                  0.24 
                  0.59 
               
               
                 Lower limit of 95% CI 
                  0.589 
                  0.766 
                  0.503 
                  0.478 
                  0.687 
                  0.302 
                  0.429 
                  0.687 
                  0.257 
               
               
                 Upper limit of 95% CI 
                  3.56 
                  4.96 
                  4.06 
                  2.94 
                  4.36 
                  2.48 
                  2.65 
                  4.36 
                  2.16 
               
               
                 OR Quartile 4 
                  3.21 
                  2.75 
                  1.27 
                  2.44 
                  2.54 
                  0.981 
                  2.28 
                  2.54 
                  0.889 
               
               
                 p Value 
                  0.045 
                  0.062 
                  0.70 
                  0.13 
                  0.085 
                  0.97 
                  0.16 
                  0.085 
                  0.85 
               
               
                 Lower limit of 95% CI 
                  1.02 
                  0.949 
                  0.377 
                  0.777 
                  0.881 
                  0.295 
                  0.724 
                  0.881 
                  0.267 
               
               
                 Upper limit of 95% CI 
                 10.1 
                  7.97 
                  4.29 
                  7.66 
                  7.35 
                  3.26 
                  7.15 
                  7.35 
                  2.96 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLLE 11.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts at 72 hours after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.612 
                  0.614 
                  0.656 
                  0.593 
                  0.656 
                  0.593 
               
               
                 Average 
                  0.849 
                  0.886 
                  0.864 
                  0.872 
                  0.864 
                  0.872 
               
               
                 Stdev 
                  0.892 
                  0.827 
                  0.901 
                  0.821 
                  0.901 
                  0.821 
               
               
                 p (t-test) 
                   
                  0.85 
                   
                  0.97 
                   
                  0.97 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 36 
                 38 
                 35 
                 39 
                 35 
                 39 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.561 
                  0.643 
                  0.561 
                  0.643 
                  0.561 
                  0.643 
               
               
                 Average 
                  0.815 
                  0.927 
                  0.815 
                  0.927 
                  0.815 
                  0.927 
               
               
                 Stdev 
                  0.853 
                  0.872 
                  0.853 
                  0.872 
                  0.853 
                  0.872 
               
               
                 p (t-test) 
                   
                  0.60 
                   
                  0.60 
                   
                  0.60 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 44 
                 29 
                 44 
                 29 
                 44 
                 29 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.625 
                  0.605 
                  0.656 
                  0.575 
                  0.656 
                  0.575 
               
               
                 Average 
                  0.735 
                  0.907 
                  0.759 
                  0.889 
                  0.759 
                  0.889 
               
               
                 Stdev 
                  0.385 
                  0.910 
                  0.383 
                  0.901 
                  0.383 
                  0.901 
               
               
                 p (t-test) 
                   
                  0.38 
                   
                  0.50 
                   
                  0.50 
               
               
                 Min 
                  0.200 
                  0.172 
                  0.200 
                  0.172 
                  0.200 
                  0.172 
               
               
                 Max 
                  1.47 
                  4.60 
                  1.47 
                  4.60 
                  1.47 
                  4.60 
               
               
                 n (Patient) 
                 18 
                 30 
                 17 
                 31 
                 17 
                 31 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.54 
                  0.58 
                  0.48 
                  0.53 
                  0.58 
                  0.45 
                  0.53 
                  0.58 
                  0.45 
               
               
                 SE 
                  0.067 
                  0.069 
                  0.087 
                  0.067 
                  0.069 
                  0.087 
                  0.067 
                  0.069 
                  0.087 
               
               
                 p Value 
                  0.51 
                  0.26 
                  0.81 
                  0.69 
                  0.26 
                  0.58 
                  0.69 
                  0.26 
                  0.58 
               
               
                 nCohort Recovered 
                 36 
                 44 
                 18 
                 35 
                 44 
                 17 
                 35 
                 44 
                 17 
               
               
                 nCohort Non-recovered 
                 38 
                 29 
                 30 
                 39 
                 29 
                 31 
                 39 
                 29 
                 31 
               
               
                 Cutoff Quartile 2 
                  0.375 
                  0.374 
                  0.397 
                  0.375 
                  0.374 
                  0.397 
                  0.375 
                  0.374 
                  0.397 
               
               
                 Sensitivity 
                 82% 
                 83% 
                 73% 
                 79% 
                 83% 
                 71% 
                 79% 
                 83% 
                 71% 
               
               
                 Specificity 
                 33% 
                 32% 
                 22% 
                 31% 
                 32% 
                 18% 
                 31% 
                 32% 
                 18% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.593 
                  0.614 
                  0.614 
                  0.593 
                  0.614 
                  0.614 
                  0.593 
                  0.614 
               
               
                 Sensitivity 
                 50% 
                 52% 
                 50% 
                 49% 
                 52% 
                 48% 
                 49% 
                 52% 
                 48% 
               
               
                 Specificity 
                 50% 
                 52% 
                 50% 
                 49% 
                 52% 
                 47% 
                 49% 
                 52% 
                 47% 
               
               
                 Cutoff Quartile 4 
                  1.03 
                  1.00 
                  1.05 
                  1.03 
                  1.00 
                  1.05 
                  1.03 
                  1.00 
                  1.05 
               
               
                 Sensitivity 
                 32% 
                 34% 
                 27% 
                 31% 
                 34% 
                 26% 
                 31% 
                 34% 
                 26% 
               
               
                 Specificity 
                 81% 
                 82% 
                 78% 
                 80% 
                 82% 
                 76% 
                 80% 
                 82% 
                 76% 
               
               
                 OR Quartile 2 
                  2.21 
                  2.24 
                  0.786 
                  1.78 
                  2.24 
                  0.524 
                  1.78 
                  2.24 
                  0.524 
               
               
                 p Value 
                  0.15 
                  0.17 
                  0.73 
                  0.29 
                  0.17 
                  0.39 
                  0.29 
                  0.17 
                  0.39 
               
               
                 Lower limit of 95% CI 
                  0.757 
                  0.707 
                  0.199 
                  0.618 
                  0.707 
                  0.121 
                  0.618 
                  0.707 
                  0.121 
               
               
                 Upper limit of 95% CI 
                  6.48 
                  7.10 
                  3.11 
                  5.10 
                  7.10 
                  2.27 
                  5.10 
                  7.10 
                  2.27 
               
               
                 OR Quartile 3 
                  1.00 
                  1.17 
                  1.00 
                  0.897 
                  1.17 
                  0.833 
                  0.897 
                  1.17 
                  0.833 
               
               
                 p Value 
                  1.0 
                  0.74 
                  1.0 
                  0.82 
                  0.74 
                  0.76 
                  0.82 
                  0.74 
                  0.76 
               
               
                 Lower limit of 95% CI 
                  0.402 
                  0.459 
                  0.311 
                  0.360 
                  0.459 
                  0.255 
                  0.360 
                  0.459 
                  0.255 
               
               
                 Upper limit of 95% CI 
                  2.49 
                  3.00 
                  3.22 
                  2.24 
                  3.00 
                  2.72 
                  2.24 
                  3.00 
                  2.72 
               
               
                 OR Quartile 4 
                  1.91 
                  2.37 
                  1.27 
                  1.78 
                  2.37 
                  1.13 
                  1.78 
                  2.37 
                  1.13 
               
               
                 p Value 
                  0.24 
                  0.12 
                  0.73 
                  0.29 
                  0.12 
                  0.86 
                  0.29 
                  0.12 
                  0.86 
               
               
                 Lower limit of 95% CI 
                  0.655 
                  0.802 
                  0.322 
                  0.609 
                  0.802 
                  0.285 
                  0.609 
                  0.802 
                  0.285 
               
               
                 Upper limit of 95% CI 
                  5.59 
                  7.00 
                  5.03 
                  5.19 
                  7.00 
                  4.49 
                  5.19 
                  7.00 
                  4.49 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “recovered” and 
               
               
                 “non-recovered” cohorts where recovery starts within 7 days after sample collection and renal status is assessed  
               
               
                 by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period  
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.544 
                  0.765 
                  0.544 
                  0.765 
                  0.544 
                  0.765 
               
               
                 Average 
                  0.780 
                  1.00 
                  0.776 
                  0.994 
                  0.776 
                  0.994 
               
               
                 Stdev 
                  0.779 
                  0.906 
                  0.789 
                  0.883 
                  0.789 
                  0.883 
               
               
                 p (t-test) 
                   
                  0.27 
                   
                  0.27 
                   
                  0.27 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 54 
                 30 
                 52 
                 32 
                 52 
                 32 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.567 
                  0.860 
                  0.561 
                  0.981 
                  0.561 
                  0.981 
               
               
                 Average 
                  0.806 
                  1.06 
                  0.798 
                  1.07 
                  0.798 
                  1.07 
               
               
                 Stdev 
                  0.782 
                  0.965 
                  0.786 
                  0.945 
                  0.786 
                  0.945 
               
               
                 p (t-test) 
                   
                  0.29 
                   
                  0.24 
                   
                  0.24 
               
               
                 Min 
                  0.108 
                  0.217 
                  0.108 
                  0.217 
                  0.108 
                  0.217 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 59 
                 22 
                 58 
                 23 
                 58 
                 23 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Recovery Period 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
                 Recovered 
                 Non-recovered 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.539 
                  0.646 
                  0.527 
                  0.669 
                  0.522 
                  0.647 
               
               
                 Average 
                  0.788 
                  0.910 
                  0.769 
                  0.932 
                  0.768 
                  0.929 
               
               
                 Stdev 
                  0.817 
                  0.860 
                  0.802 
                  0.879 
                  0.814 
                  0.864 
               
               
                 p (t-test) 
                   
                  0.53 
                   
                  0.41 
                   
                  0.41 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
                  0.108 
                  0.172 
               
               
                 Max 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
                  4.86 
                  4.60 
               
               
                 n (Patient) 
                 40 
                 38 
                 42 
                 36 
                 41 
                 37 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Recovery Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only  
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.58 
                  0.60 
                  0.53 
                  0.60 
                  0.62 
                  0.55 
                  0.60 
                  0.62 
                  0.56 
               
               
                 SE 
                  0.066 
                  0.073 
                  0.066 
                  0.065 
                  0.071 
                  0.066 
                  0.065 
                  0.071 
                  0.065 
               
               
                 p Value 
                  0.20 
                  0.16 
                  0.61 
                  0.14 
                  0.087 
                  0.48 
                  0.14 
                  0.087 
                  0.33 
               
               
                 nCohort Recovered 
                 54 
                 59 
                 40 
                 52 
                 58 
                 42 
                 52 
                 58 
                 41 
               
               
                 nCohort Non-recovered 
                 30 
                 22 
                 38 
                 32 
                 23 
                 36 
                 32 
                 23 
                 37 
               
               
                 Cutoff Quartile 2 
                  0.372 
                  0.374 
                  0.375 
                  0.372 
                  0.374 
                  0.374 
                  0.372 
                  0.374 
                  0.374 
               
               
                 Sensitivity 
                 77% 
                 82% 
                 74% 
                 78% 
                 83% 
                 72% 
                 78% 
                 83% 
                 76% 
               
               
                 Specificity 
                 26% 
                 29% 
                 25% 
                 27% 
                 29% 
                 24% 
                 27% 
                 29% 
                 27% 
               
               
                 Cutoff Quartile 3 
                  0.614 
                  0.636 
                  0.584 
                  0.614 
                  0.636 
                  0.584 
                  0.614 
                  0.636 
                  0.584 
               
               
                 Sensitivity 
                 63% 
                 64% 
                 55% 
                 62% 
                 65% 
                 58% 
                 62% 
                 65% 
                 57% 
               
               
                 Specificity 
                 57% 
                 56% 
                 55% 
                 58% 
                 57% 
                 57% 
                 58% 
                 57% 
                 56% 
               
               
                 Cutoff Quartile 4 
                  1.04 
                  1.04 
                  0.995 
                  1.04 
                  1.04 
                  0.995 
                  1.04 
                  1.04 
                  0.995 
               
               
                 Sensitivity 
                 37% 
                 36% 
                 34% 
                 38% 
                 39% 
                 36% 
                 38% 
                 39% 
                 35% 
               
               
                 Specificity 
                 81% 
                 80% 
                 82% 
                 83% 
                 81% 
                 83% 
                 83% 
                 81% 
                 83% 
               
               
                 OR Quartile 2 
                  1.15 
                  1.82 
                  0.933 
                  1.32 
                  1.97 
                  0.812 
                  1.32 
                  1.97 
                  1.14 
               
               
                 p Value 
                  0.79 
                  0.34 
                  0.89 
                  0.60 
                  0.28 
                  0.69 
                  0.60 
                  0.28 
                  0.80 
               
               
                 Lower limit of 95% CI 
                  0.406 
                  0.537 
                  0.338 
                  0.466 
                  0.583 
                  0.294 
                  0.466 
                  0.583 
                  0.411 
               
               
                 Upper limit of 95% CI 
                  3.26 
                  6.18 
                  2.58 
                  3.72 
                  6.65 
                  2.25 
                  3.72 
                  6.65 
                  3.16 
               
               
                 OR Quartile 3 
                  2.33 
                  2.22 
                  1.51 
                  2.27 
                  2.47 
                  1.87 
                  2.27 
                  2.47 
                  1.68 
               
               
                 p Value 
                  0.071 
                  0.12 
                  0.37 
                  0.075 
                  0.077 
                  0.17 
                  0.075 
                  0.077 
                  0.26 
               
               
                 Lower limit of 95% CI 
                  0.930 
                  0.810 
                  0.618 
                  0.922 
                  0.908 
                  0.758 
                  0.922 
                  0.908 
                  0.684 
               
               
                 Upper limit of 95% CI 
                  5.83 
                  6.09 
                  3.69 
                  5.61 
                  6.75 
                  4.60 
                  5.61 
                  6.75 
                  4.11 
               
               
                 OR Quartile 4 
                  2.55 
                  2.24 
                  2.45 
                  2.87 
                  2.75 
                  2.83 
                  2.87 
                  2.75 
                  2.63 
               
               
                 p Value 
                  0.070 
                  0.14 
                  0.096 
                  0.042 
                  0.063 
                  0.054 
                  0.042 
                  0.063 
                  0.073 
               
               
                 Lower limit of 95% CI 
                  0.927 
                  0.764 
                  0.853 
                  1.04 
                  0.948 
                  0.980 
                  1.04 
                  0.948 
                  0.914 
               
               
                 Upper limit of 95% CI 
                  7.00 
                  6.56 
                  7.04 
                  7.90 
                  7.96 
                  8.15 
                  7.90 
                  7.96 
                  7.57 
               
               
                   
               
            
           
         
       
     
     Example 12. Use of C-C Motif Chemokine 14 for Evaluating Renal Status in Patients Admitted to the ICU: Persistent at RIFLE F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 14 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output. Two cohorts are defined to represent a “persistent” and a “non-persistent” population. “Persistent” indicates those patients whose minimum RIFLE stage during a period of 24, 48 or 72 hours is failure (F) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. “Non-persistent” indicates those patients who are not persistent at failure (F) and whose minimum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0), risk of injury (R), or injury (I) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. If a patient dies after failure (F) or is placed on renal replacement therapy (RRT) at any time from sample collection to 24, 48, 72, 96 or 168 hours after sample collection, the patient is considered “persistent”. 
     The ability to distinguish the “persistent” and “non-persistent” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 12.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the  
               
               
                 “persistent” and “non-persistent” cohorts where persistence starts within 24 hours  
               
               
                 after sample collection and renal status is assessed by serum  
               
               
                 creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.704 
                 2.96 
                 0.768 
                 5.37 
                 0.779 
                 5.21 
               
               
                 Average 
                 1.43 
                 3.29 
                 1.49 
                 4.09 
                 1.56 
                 3.92 
               
               
                 Stdev 
                 1.69 
                 2.40 
                 1.68 
                 2.44 
                 1.76 
                 2.45 
               
               
                 p (t-test) 
                   
                 1.7E−4 
                   
                 5.3E−6 
                   
                 7.5E−5 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 61 
                 22 
                 69 
                 14 
                 70 
                 13 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.801 
                 3.80 
                 0.812 
                 2.87 
                 1.03 
                 2.16 
               
               
                 Average 
                 1.61 
                 3.63 
                 1.70 
                 3.64 
                 1.83 
                 3.08 
               
               
                 Stdev 
                 1.80 
                 2.57 
                 1.87 
                 2.68 
                 1.98 
                 2.66 
               
               
                 p (t-test) 
                   
                 7.2E−4 
                   
                 0.0037 
                   
                 0.090 
               
               
                 Min 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 66 
                 14 
                 69 
                 11 
                 71 
                 9 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.704 
                 2.87 
                 0.768 
                 5.53 
                 0.768 
                 5.53 
               
               
                 Average 
                 1.55 
                 3.19 
                 1.54 
                 4.72 
                 1.54 
                 4.72 
               
               
                 Stdev 
                 1.81 
                 2.32 
                 1.75 
                 1.99 
                 1.75 
                 1.99 
               
               
                 p (t-test) 
                   
                 0.0027 
                   
                 2.9E−6 
                   
                 2.9E−6 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.121 
                 1.03 
                 0.121 
                 1.03 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 61 
                 17 
                 69 
                 9 
                 69 
                 9 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.73     
                  0.72     
                  0.74     
                  0.79     
                  0.71     
                   0.87     
                  0.77     
                  0.64     
                  0.87     
               
               
                 SE 
                  0.067    
                  0.082     
                  0.075     
                  0.075    
                  0.092    
                   0.077     
                  0.080     
                  0.10     
                  0.077     
               
               
                 p Value 
                 5.0E−4 
                  0.0066    
                  0.0015    
                 1.1E−4 
                  0.023    
                 1.2E−6 
                 7.8E−4 
                  0.17     
                 1.2E−6 
               
               
                 nCohort  
                 61        
                 66       
                 61        
                 69        
                 69        
                  69       
                 70       
                 71        
                  69       
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 22        
                 14       
                 17        
                 14        
                 11        
                  9       
                 13       
                  9        
                  9       
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                  0.467    
                  0.457     
                  0.483     
                  0.467    
                  0.457    
                  0.483     
                  0.467     
                  0.457    
                  0.483     
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 91%     
                 86%    
                 94%    
                 93%    
                 82%    
                 100%    
                 92%    
                 78%    
                 100%    
               
               
                 Specificity 
                 31%     
                 27%    
                 31%    
                 29%    
                 26%    
                  29%    
                 29%    
                 25%    
                  29%    
               
               
                 Cutoff  
                  1.04     
                  1.04     
                  1.03     
                  1.04     
                  1.04     
                  1.03     
                  1.04     
                  1.04     
                  1.03     
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 73%     
                 71%    
                 76%    
                 79%    
                 73%    
                  89%    
                 77%    
                 67%    
                  89%    
               
               
                 Specificity 
                 57%     
                 55%    
                 57%    
                 55%    
                 54%    
                  55%    
                 54%    
                 52%    
                  55%    
               
               
                 Cutoff  
                  2.82     
                  2.88     
                  2.84     
                  2.82     
                  2.88     
                  2.84     
                  2.82     
                  2.88     
                  2.84     
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 55%     
                 50%    
                 53%    
                 64%    
                 45%    
                  78%    
                 62%    
                 33%    
                  78%    
               
               
                 Specificity 
                 85%     
                 80%    
                 82%    
                 83%    
                 78%    
                  81%    
                 81%    
                 76%    
                  81%    
               
               
                 OR  
                  4.52     
                  2.25     
                  7.24     
                  5.31     
                  1.59     
                  7.87     
                  4.80     
                  1.19     
                  7.87     
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.057    
                  0.32     
                  0.064     
                  0.12     
                  0.58     
                  0.16     
                  0.14     
                  0.84     
                  0.16     
               
               
                 Lower limit  
                  0.959    
                  0.458     
                  0.894     
                  0.650    
                  0.313    
                  0.437     
                  0.585     
                  0.226    
                  0.437     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 21.3      
                 11.1     
                 58.6      
                 43.3     
                  8.06     
                 142       
                 39.4      
                  6.25     
                 142       
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  3.59     
                  3.00     
                  4.38     
                  4.49     
                  3.08     
                  9.81     
                  3.96     
                  2.18     
                  9.81     
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.019    
                  0.087     
                  0.019     
                  0.031    
                  0.12     
                  0.036     
                  0.050     
                  0.30     
                  0.036     
               
               
                 Lower limit  
                  1.24     
                  0.854     
                  1.28     
                  1.15     
                  0.754    
                  1.16     
                  1.00     
                  0.504    
                  1.16     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 10.4      
                 10.5      
                 15.0      
                 17.5     
                 12.6     
                  82.7      
                 15.6      
                  9.39     
                  82.7      
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  6.93     
                  4.08     
                  5.11     
                  8.55     
                  3.00     
                   15.1      
                  7.02     
                  1.59     
                  15.1      
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 5.5E−4 
                  0.023     
                  0.0056    
                 8.3E−4 
                  0.10     
                  0.0016    
                  0.0026    
                  0.54     
                  0.0016    
               
               
                 Lower limit  
                  2.31     
                  1.21     
                  1.61     
                  2.43     
                  0.803    
                  2.80     
                  1.97     
                  0.358    
                  2.80     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 20.8      
                 13.7      
                 16.2      
                 30.1     
                 11.2     
                  81.2      
                 25.0      
                  7.04     
                  81.2      
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.685 
                 2.87 
                 0.763 
                 5.21 
                 0.768 
                 4.04 
               
               
                 Average 
                 1.35 
                 3.26 
                 1.42 
                 3.91 
                 1.49 
                 3.76 
               
               
                 Stdev 
                 1.59 
                 2.41 
                 1.59 
                 2.48 
                 1.69 
                 2.49 
               
               
                 p (t-test) 
                   
                 5.3E−5 
                   
                 2.5E−6 
                   
                 3.6E−5 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 58 
                 25 
                 66 
                 17 
                 67 
                 16 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.801 
                 3.80 
                 0.812 
                 2.87 
                 1.03 
                 2.16 
               
               
                 Average 
                 1.61 
                 3.63 
                 1.70 
                 3.64 
                 1.83 
                 3.08 
               
               
                 Stdev 
                 1.80 
                 2.57 
                 1.87 
                 2.68 
                 1.98 
                 2.66 
               
               
                 p (t-test) 
                   
                 7.2E−4 
                   
                 0.0037 
                   
                 0.090 
               
               
                 Min 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 66 
                 14 
                 69 
                 11 
                 71 
                 9 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.665 
                 2.87 
                 0.757 
                 5.53 
                 0.757 
                 5.53 
               
               
                 Average 
                 1.38 
                 3.32 
                 1.40 
                 4.45 
                 1.40 
                 4.45 
               
               
                 Stdev 
                 1.63 
                 2.39 
                 1.57 
                 2.24 
                 1.57 
                 2.24 
               
               
                 p (t-test) 
                   
                 1.1E−4 
                   
                 8.5E−8 
                   
                 8.5E−8 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.121 
                 0.448 
                 0.121 
                 0.448 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 57 
                 21 
                 65 
                 13 
                 65 
                 13 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.74     
                  0.72     
                  0.76     
                  0.78     
                  0.71     
                  0.85     
                  0.76      
                  0.64     
                  0.85     
               
               
                 SE 
                  0.063    
                  0.082     
                  0.067     
                  0.070    
                  0.092    
                  0.069    
                  0.074     
                  0.10     
                  0.069    
               
               
                 p Value 
                 1.7E−4 
                  0.0066    
                 9.8E−5 
                 6.5E−5 
                  0.023    
                 3.5E−7 
                 4.5E−4 
                  0.17     
                 3.5E−7 
               
               
                 nCohort  
                 58       
                 66       
                 57       
                 66       
                 69       
                 65       
                 67       
                 71       
                 65       
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 25       
                 14       
                 21       
                 17       
                 11       
                 13       
                 16       
                  9       
                 13       
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                  0.467    
                  0.457     
                  0.483     
                  0.467    
                  0.457    
                  0.483    
                  0.467    
                  0.457    
                  0.483    
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 88%    
                 86%    
                 90%    
                 88%    
                 82%    
                 92%    
                 88%    
                 78%    
                 92%    
               
               
                 Specificity 
                 31%    
                 27%    
                 32%    
                 29%    
                 26%    
                 29%    
                 28%    
                 25%    
                 29%    
               
               
                 Cutoff  
                  1.04     
                  1.04     
                  1.03     
                  1.04     
                  1.04     
                  1.03     
                  1.04      
                  1.04     
                  1.03     
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 72%    
                 71%    
                 76%    
                 76%    
                 73%    
                 85%    
                 75%    
                 67%    
                 85%    
               
               
                 Specificity 
                 59%    
                 55%    
                 60%    
                 56%    
                 54%    
                 57%    
                 55%    
                 52%    
                 57%    
               
               
                 Cutoff  
                  2.82     
                  2.88     
                  2.84     
                  2.82     
                  2.88     
                  2.84     
                  2.82      
                  2.88     
                  2.84     
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 52%    
                 50%    
                 52%    
                 59%    
                 45%    
                 69%    
                 56%    
                 33%    
                 69%    
               
               
                 Specificity 
                 86%    
                 80%    
                 84%    
                 83%    
                 78%    
                 83%    
                 82%    
                 76%    
                 83%    
               
               
                 OR  
                  3.30     
                  2.25     
                  4.38     
                  3.03     
                  1.59     
                  4.96     
                  2.77      
                  1.19     
                  4.96     
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.078    
                  0.32     
                  0.063     
                  0.17     
                  0.58     
                  0.14     
                  0.20      
                  0.84     
                  0.14     
               
               
                 Lower limit  
                  0.874    
                  0.458     
                  0.921     
                  0.632    
                  0.313    
                  0.602    
                  0.574     
                  0.226    
                  0.602    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 12.5     
                 11.1      
                 20.9      
                 14.6     
                  8.06     
                 40.8     
                 13.4      
                  6.25     
                 40.8     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  3.64     
                  3.00     
                  4.73     
                  4.15     
                  3.08     
                  7.27     
                  3.70      
                  2.18     
                  7.27     
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.013    
                  0.087     
                  0.0073    
                  0.022    
                  0.12     
                  0.014    
                  0.037     
                  0.30     
                  0.014    
               
               
                 Lower limit  
                  1.32     
                  0.854     
                  1.52     
                  1.22     
                  0.754    
                  1.49     
                  1.08      
                  0.504    
                  1.49     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 10.1     
                 10.5      
                 14.7      
                 14.1     
                 12.6     
                 35.4     
                 12.7      
                  9.39     
                 35.4     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  6.77     
                  4.08     
                  5.87     
                  7.14     
                  3.00     
                 11.0     
                  5.89      
                  1.59     
                 11.0     
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 5.4E−4 
                  0.023     
                  0.0018    
                 9.2E−4 
                  0.10     
                 4.6E−4 
                  0.0029    
                  0.54     
                 4.6E−4 
               
               
                 Lower limit  
                  2.29     
                  1.21     
                  1.93     
                  2.23     
                  0.803    
                  2.88     
                  1.83      
                  0.358    
                  2.88     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 20.0     
                 13.7      
                 17.9      
                 22.8     
                 11.2     
                 42.4     
                 19.0      
                  7.04     
                 42.4     
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.665 
                 2.56 
                 0.768 
                 4.04 
                 0.779 
                 2.87 
               
               
                 Average 
                 1.36 
                 3.16 
                 1.43 
                 3.73 
                 1.50 
                 3.58 
               
               
                 Stdev 
                 1.60 
                 2.42 
                 1.60 
                 2.52 
                 1.70 
                 2.52 
               
               
                 p (t-test) 
                   
                 1.3E−4 
                   
                 1.0E−5 
                   
                 1.2E−4 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 57 
                 26 
                 65 
                 18 
                 66 
                 17 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.812 
                 2.87 
                 0.812 
                 2.87 
                 1.03 
                 2.16 
               
               
                 Average 
                 1.63 
                 3.44 
                 1.70 
                 3.64 
                 1.83 
                 3.08 
               
               
                 Stdev 
                 1.81 
                 2.59 
                 1.87 
                 2.68 
                 1.98 
                 2.66 
               
               
                 p (t-test) 
                   
                 0.0020 
                   
                 0.0037 
                   
                 0.090 
               
               
                 Min 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
                 0.121 
                 0.422 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 65 
                 15 
                 69 
                 11 
                 71 
                 9 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.653 
                 2.82 
                 0.768 
                 5.21 
                 0.736 
                 5.37 
               
               
                 Average 
                 1.40 
                 3.20 
                 1.42 
                 3.95 
                 1.41 
                 4.18 
               
               
                 Stdev 
                 1.64 
                 2.40 
                 1.59 
                 2.45 
                 1.58 
                 2.37 
               
               
                 p (t-test) 
                   
                 2.8E−4 
                   
                 4.3E−6 
                   
                 7.2E−7 
               
               
                 Min 
                 0.194 
                 0.121 
                 0.121 
                 0.448 
                 0.121 
                 0.448 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 56 
                 22 
                 63 
                 15 
                 64 
                 14 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.73 
                 0.70 
                 0.75 
                 0.76 
                 0.71 
                 0.80 
                 0.74 
                 0.64 
                 0.83 
               
               
                 SE 
                 0.063 
                 0.081 
                 0.066 
                 0.070 
                 0.092 
                 0.072 
                 0.074 
                 0.10 
                 0.071 
               
               
                 p Value 
                 3.0E−4 
                 0.011 
                 2.0E−4 
                 1.7E−4 
                 0.023 
                 2.8E−5 
                 9.7E−4 
                 0.17 
                 4.5E−6 
               
               
                 nCohort Non-persistent 
                 57 
                 65 
                 56 
                 65 
                 69 
                 63 
                 66 
                 71 
                 64 
               
               
                 nCohort Persistent 
                 26 
                 15 
                 22 
                 18 
                 11 
                 15 
                 17 
                 9 
                 14 
               
               
                 Cutoff Quartile 2 
                 0.467 
                 0.457 
                 0.483 
                 0.467 
                 0.457 
                 0.483 
                 0.467 
                 0.457 
                 0.483 
               
               
                 Sensitivity 
                 88% 
                 87% 
                 91% 
                 89% 
                 82% 
                 93% 
                 88% 
                 78% 
                 93% 
               
               
                 Specificity 
                 32% 
                 28% 
                 32% 
                 29% 
                 26% 
                 30% 
                 29% 
                 25% 
                 30% 
               
               
                 Cutoff Quartile 3 
                 1.04 
                 1.04 
                 1.03 
                 1.04 
                 1.04 
                 1.03 
                 1.04 
                 1.04 
                 1.03 
               
               
                 Sensitivity 
                 69% 
                 67% 
                 73% 
                 72% 
                 73% 
                 73% 
                 71% 
                 67% 
                 79% 
               
               
                 Specificity 
                 58% 
                 54% 
                 59% 
                 55% 
                 54% 
                 56% 
                 55% 
                 52% 
                 56% 
               
               
                 Cutoff Quartile 4 
                 2.82 
                 2.88 
                 2.84 
                 2.82 
                 2.88 
                 2.84 
                 2.82 
                 2.88 
                 2.84 
               
               
                 Sensitivity 
                 50% 
                 47% 
                 50% 
                 56% 
                 45% 
                 60% 
                 53% 
                 33% 
                 64% 
               
               
                 Specificity 
                 86% 
                 80% 
                 84% 
                 83% 
                 78% 
                 83% 
                 82% 
                 76% 
                 83% 
               
               
                 OR Quartile 2 
                 3.54 
                 2.49 
                 4.74 
                 3.30 
                 1.59 
                 6.05 
                 3.03 
                 1.19 
                 5.49 
               
               
                 p Value 
                 0.062 
                 0.26 
                 0.050 
                 0.13 
                 0.58 
                 0.093 
                 0.17 
                 0.84 
                 0.11 
               
               
                 Lower limit of 95% CI 
                 0.939 
                 0.510 
                 0.997 
                 0.691 
                 0.313 
                 0.741 
                 0.632 
                 0.226 
                 0.670 
               
               
                 Upper limit of 95% CI 
                 13.3 
                 12.1 
                 22.5 
                 15.8 
                 8.06 
                 49.3 
                 14.6 
                 6.25 
                 45.0 
               
               
                 OR Quartile 3 
                 3.09 
                 2.33 
                 3.83 
                 3.23 
                 3.08 
                 3.44 
                 2.88 
                 2.18 
                 4.71 
               
               
                 p Value 
                 0.025 
                 0.16 
                 0.015 
                 0.044 
                 0.12 
                 0.052 
                 0.071 
                 0.30 
                 0.026 
               
               
                 Lower limit of 95% CI 
                 1.16 
                 0.718 
                 1.30 
                 1.03 
                 0.754 
                 0.987 
                 0.912 
                 0.504 
                 1.20 
               
               
                 Upper limit of 95% CI 
                 8.28 
                 7.59 
                 11.3 
                 10.1 
                 12.6 
                 12.0 
                 9.10 
                 9.39 
                 18.5 
               
               
                 OR Quartile 4 
                 6.12 
                 3.50 
                 5.22 
                 6.14 
                 3.00 
                 7.09 
                 5.06 
                 1.59 
                 8.67 
               
               
                 p Value 
                 9.2E−4 
                 0.038 
                 0.0032 
                 0.0017 
                 0.10 
                 0.0017 
                 0.0053 
                 0.54 
                 8.7E−4 
               
               
                 Lower limit of 95% CI 
                 2.10 
                 1.07 
                 1.74 
                 1.98 
                 0.803 
                 2.09 
                 1.62 
                 0.358 
                 2.43 
               
               
                 Upper limit of 95% CI 
                 17.9 
                 11.4 
                 15.7 
                 19.1 
                 11.2 
                 24.0 
                 15.8 
                 7.04 
                 30.9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.665 
                  2.56   
                  0.779 
                  2.87   
                  0.790 
                  2.56  
               
               
                 Average 
                  1.36  
                  3.16   
                  1.44  
                  3.57   
                  1.51  
                  3.42  
               
               
                 Stdev 
                  1.60  
                  2.42   
                  1.61  
                  2.55   
                  1.71  
                  2.54  
               
               
                 p (t-test) 
                   
                 1.3E−4 
                   
                 3.7E−5 
                   
                 3.5E−4 
               
               
                 Min 
                  0.194 
                  0.121  
                  0.121 
                  0.422  
                  0.121 
                  0.422 
               
               
                 Max 
                  7.86  
                  6.66   
                  7.86  
                  6.66   
                  7.86  
                  6.66  
               
               
                 n (Patient) 
                 57     
                 26    
                 64    
                 19    
                 65    
                 18    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.812 
                  2.87   
                  0.922 
                  2.51   
                  1.03  
                  2.07  
               
               
                 Average 
                  1.63  
                  3.44   
                  1.72  
                  3.38   
                  1.84  
                  2.83  
               
               
                 Stdev 
                  1.81  
                  2.59   
                  1.87  
                  2.70   
                  1.99  
                  2.62  
               
               
                 p (t-test) 
                   
                  0.0020 
                   
                  0.0098 
                   
                  0.16  
               
               
                 Min 
                  0.121 
                  0.422  
                  0.121 
                  0.422  
                  0.121 
                  0.422 
               
               
                 Max 
                  7.86  
                  6.66   
                  7.86  
                  6.66   
                  7.86  
                  6.66  
               
               
                 n (Patient) 
                 65    
                 15    
                 68    
                 12    
                 70    
                 10    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.653 
                  2.82  
                  0.779 
                  4.04  
                  0.768 
                  5.21  
               
               
                 Average 
                  1.40  
                  3.20  
                  1.43  
                  3.74  
                  1.42  
                  3.95  
               
               
                 Stdev 
                  1.64  
                  2.40  
                  1.60  
                  2.51  
                  1.59  
                  2.46  
               
               
                 p (t-test) 
                   
                 2.8E−4 
                   
                 2.1E−5 
                   
                 4.6E−6 
               
               
                 Min 
                  0.194 
                  0.1216  
                  0.121 
                  0.4486  
                  0.121 
                  0.448 
               
               
                 Max 
                  7.86  
                  6.66  
                  7.86  
                  6.66  
                  7.86  
                  6.66  
               
               
                 n (Patient) 
                 56    
                 22    
                 62    
                 16    
                 63    
                 15    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.73 
                 0.70 
                 0.75 
                 0.75 
                 0.68 
                 0.78 
                 0.72 
                 0.62 
                 0.80 
               
               
                 SE 
                 0.063 
                 0.081 
                 0.066 
                 0.070 
                 0.090 
                 0.073 
                 0.073 
                 0.10 
                 0.073 
               
               
                 p Value 
                 3.0E−4 
                 0.011 
                 2.0E−4 
                 4.8E−4 
                 0.044 
                 1.4E−4 
                 0.0023 
                 0.24 
                 4.1E−5 
               
               
                 nCohort  
                 57 
                 65 
                 56 
                 64 
                 68 
                 62 
                 65 
                 70 
                 63 
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 26 
                 15 
                 22 
                 19 
                 12 
                 16 
                 18 
                 10 
                 15 
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 0.467 
                 0.457 
                 0.483 
                 0.467 
                 0.457 
                 0.483 
                 0.467 
                 0.457 
                 0.483 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 88% 
                 87% 
                 91% 
                 89% 
                 83% 
                 94% 
                 89% 
                 80% 
                 93% 
               
               
                 Specificity 
                 32% 
                 28% 
                 32% 
                 30% 
                 26% 
                 31% 
                 29% 
                 26% 
                 30% 
               
               
                 Cutoff  
                 1.04 
                 1.04 
                 1.03 
                 1.04 
                 1.04 
                 1.03 
                 1.04 
                 1.04 
                 1.03 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 69% 
                 67% 
                 73% 
                 68% 
                 67% 
                 69% 
                 67% 
                 60% 
                 73% 
               
               
                 Specificity 
                 58% 
                 54% 
                 59% 
                 55% 
                 53% 
                 55% 
                 54% 
                 51% 
                 56% 
               
               
                 Cutoff  
                 2.82 
                 2.88 
                 2.84 
                 2.82 
                 2.88 
                 2.84 
                 2.82 
                 2.88 
                 2.84 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 50% 
                 47% 
                 50% 
                 53% 
                 42% 
                 56% 
                 50% 
                 30% 
                 60% 
               
               
                 Specificity 
                 86% 
                 80% 
                 84% 
                 83% 
                 78% 
                 82% 
                 82% 
                 76% 
                 83% 
               
               
                 OR  
                 3.54 
                 2.49 
                 4.74 
                 3.59 
                 1.80 
                 6.63 
                 3.30 
                 1.38 
                 6.05 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.062 
                 0.26 
                 0.050 
                 0.11 
                 0.47 
                 0.077 
                 0.13 
                 0.70 
                 0.093 
               
               
                 Lower limit  
                 0.939 
                 0.510 
                 0.997 
                 0.754 
                 0.359 
                 0.816 
                 0.691 
                 0.269 
                 0.741 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 13.3 
                 12.1 
                 22.5 
                 17.1 
                 9.01 
                 53.9 
                 15.8 
                 7.14 
                 49.3 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 3.09 
                 2.33 
                 3.83 
                 2.61 
                 2.25 
                 2.67 
                 2.33 
                 1.59 
                 3.44 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.025 
                 0.16 
                 0.015 
                 0.083 
                 0.22 
                 0.100 
                 0.13 
                 0.50 
                 0.052 
               
               
                 Lower limit  
                 1.16 
                 0.718 
                 1.30 
                 0.883 
                 0.619 
                 0.830 
                 0.781 
                 0.412 
                 0.987 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 8.28 
                 7.59 
                 11.3 
                 7.74 
                 8.18 
                 8.60 
                 6.97 
                 6.12 
                 12.0 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 6.12 
                 3.50 
                 5.22 
                 5.35 
                 2.52 
                 5.96 
                 4.42 
                 1.34 
                 7.09 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 9.2E−4 
                 0.038 
                 0.0032 
                 0.0031 
                 0.16 
                 0.0031 
                 0.0091 
                 0.70 
                 0.0017 
               
               
                 Lower limit  
                 2.10 
                 1.07 
                 1.74 
                 1.76 
                 0.700 
                 1.83 
                 1.45 
                 0.311 
                 2.09 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 17.9 
                 11.4 
                 15.7 
                 16.2 
                 9.10 
                 19.5 
                 13.5 
                 5.75 
                 24.0 
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) 
               
               
                 in urine samples for the “persistent” and “non-persistent” cohorts 
               
               
                 where persistence starts within 168 hours after sample collection 
               
               
                 and renal status is assessed by serum creatinine (sCr) only, urine output (UO) 
               
               
                 only, or serum creatinine or urine outpu tRIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.639 
                  2.77  
                  0.736 
                  2.77   
                 0.779  
                 2.77  
               
               
                 Average 
                  1.26  
                  3.18  
                  1.37  
                  3.38   
                 1.45  
                 3.34  
               
               
                 Stdev 
                  1.52  
                  2.36  
                  1.55  
                  2.51   
                 1.65  
                 2.51  
               
               
                 p (t-test) 
                   
                 2.2E−5 
                   
                 3.2E−5 
                   
                 1.7E−4 
               
               
                 Min 
                  0.194 
                  0.121 
                  0.194 
                  0.121  
                 0.194  
                 0.121 
               
               
                 Max 
                  7.86  
                  6.66  
                  7.86  
                  6.66   
                 7.86  
                 6.66  
               
               
                 n (Patient) 
                 54      
                 29      
                 60      
                 23       
                 62      
                 21      
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.801 
                  3.80  
                  0.812 
                  2.87   
                 0.922 
                 2.51  
               
               
                 Average 
                  1.56  
                  3.58  
                  1.66  
                  3.56   
                 1.73  
                 3.34  
               
               
                 Stdev 
                  1.75  
                  2.56  
                  1.82  
                  2.66   
                 1.89  
                 2.65  
               
               
                 p (t-test) 
                   
                 3.6E−4 
                   
                  0.0021 
                   
                 0.013 
               
               
                 Min 
                  0.121 
                  0.422 
                  0.121 
                  0.422  
                 0.121 
                 0.422 
               
               
                 Max 
                  7.86  
                  6.66  
                  7.86  
                  6.66   
                 7.86  
                 6.66  
               
               
                 n (Patient) 
                 64      
                 16      
                 67      
                 13       
                 68      
                 12      
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.639 
                  2.82  
                 0.717 
                  2.82   
                  0.704 
                  2.87  
               
               
                 Average 
                  1.31  
                  3.25  
                 1.37  
                  3.46   
                  1.36  
                  3.60  
               
               
                 Stdev 
                  1.56  
                  2.36  
                 1.55  
                  2.50   
                  1.54  
                  2.48  
               
               
                 p (t-test) 
                   
                 4.7E−5 
                   
                 3.6E−5 
                   
                 1.1E−5 
               
               
                 Min 
                  0.194 
                  0.121 
                 0.194 
                  0.121  
                  0.194 
                  0.121 
               
               
                 Max 
                  7.86  
                  6.66  
                 7.86  
                  6.66   
                  7.86  
                  6.66  
               
               
                 n (Patient) 
                 54      
                 24      
                 58      
                 20       
                 59      
                 19      
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.76 
                 0.72 
                 0.77 
                 0.73 
                 0.71 
                 0.75 
                 0.71 
                 0.68 
                 0.76 
               
               
                 SE 
                 0.059 
                 0.077 
                 0.062 
                 0.066 
                 0.086 
                 0.069 
                 0.070 
                 0.091 
                 0.069 
               
               
                 p Value 
                 1.4E−5 
                 0.0037 
                 1.7E−5 
                 4.9E−4 
                 0.017 
                 2.8E−4 
                 0.0027 
                 0.050 
                 1.2E−4 
               
               
                 nCohort  
                 54 
                 64 
                 54 
                 60 
                 67 
                 58 
                 62 
                 68 
                 59 
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 29 
                 16 
                 24 
                 23 
                 13 
                 20 
                 21 
                 12 
                 19 
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 0.467 
                 0.457 
                 0.483 
                 0.467 
                 0.457 
                 0.483 
                 0.467 
                 0.457 
                 0.483 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 90% 
                 88% 
                 92% 
                 87% 
                 85% 
                 90% 
                 86% 
                 83% 
                 89% 
               
               
                 Specificity 
                 33% 
                 28% 
                 33% 
                 30% 
                 27% 
                 31% 
                 29% 
                 26% 
                 31% 
               
               
                 Cutoff  
                 1.04 
                 1.04 
                 1.03 
                 1.04 
                 1.04 
                 1.03 
                 1.04 
                 1.04 
                 1.03 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 72% 
                 69% 
                 75% 
                 70% 
                 69% 
                 70% 
                 67% 
                 67% 
                 74% 
               
               
                 Specificity 
                 61% 
                 55% 
                 61% 
                 57% 
                 54% 
                 57% 
                 55% 
                 53% 
                 58% 
               
               
                 Cutoff  
                 2.82 
                 2.88 
                 2.84 
                 2.82 
                 2.88 
                 2.84 
                 2.82 
                 2.88 
                 2.84 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 48% 
                 50% 
                 50% 
                 48% 
                 46% 
                 50% 
                 48% 
                 42% 
                 53% 
               
               
                 Specificity 
                 87% 
                 81% 
                 85% 
                 83% 
                 79% 
                 83% 
                 82% 
                 78% 
                 83% 
               
               
                 OR  
                 4.33 
                 2.74 
                 5.50 
                 2.86 
                 2.02 
                 4.05 
                 2.45 
                 1.80 
                 3.73 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.030 
                 0.21 
                 0.032 
                 0.12 
                 0.39 
                 0.079 
                 0.19 
                 0.47 
                 0.099 
               
               
                 Lower limit  
                 1.15 
                 0.565 
                 1.16 
                 0.753 
                 0.408 
                 0.848 
                 0.643 
                 0.359 
                 0.779 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 16.3 
                 13.3 
                 26.0 
                 10.8 
                 10.0 
                 19.3 
                 9.37 
                 9.01 
                 17.9 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 4.12 
                 2.66 
                 4.71 
                 2.99 
                 2.61 
                 3.08 
                 2.43 
                 2.25 
                 3.81 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.0046 
                 0.10 
                 0.0047 
                 0.036 
                 0.14 
                 0.043 
                 0.093 
                 0.22 
                 0.022 
               
               
                 Lower limit  
                 1.55 
                 0.827 
                 1.61 
                 1.07 
                 0.732 
                 1.04 
                 0.862 
                 0.619 
                 1.21 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 11.0 
                 8.52 
                 13.8 
                 8.33 
                 9.32 
                 9.15 
                 6.84 
                 8.18 
                 12.0 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                 6.27 
                 4.33 
                 5.75 
                 4.58 
                 3.24 
                 4.80 
                 4.21 
                 2.52 
                 5.44 
               
               
                   
               
               
                 p Value 
                 8.4E−4 
                 0.014 
                 0.0018 
                 0.0050 
                 0.063 
                 0.0056 
                 0.0088 
                 0.16 
                 0.0032 
               
               
                 Lower limit  
                 2.13 
                 1.35 
                 1.92 
                 1.58 
                 0.940 
                 1.58 
                 1.44 
                 0.700 
                 1.76 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 18.4 
                 13.9 
                 17.2 
                 13.3 
                 11.2 
                 14.6 
                 12.4 
                 9.10 
                 16.8 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC)  
               
               
                 in EDTA samples for the “persistent” and “non-persistent” cohorts  
               
               
                 where persistence starts within 24 hours after sample collection and renal status 
               
               
                 is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine 
               
               
                 output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 231   
                 285     
                 233   
                 293    
                 235   
                 285    
               
               
                 Average 
                 248   
                 313     
                 250   
                 335    
                 250   
                 337    
               
               
                 Stdev 
                 111   
                 148     
                 108   
                 166    
                 107   
                 172    
               
               
                 p (t-test) 
                   
                   0.031  
                   
                   0.013 
                   
                   0.014 
               
               
                 Min 
                  73.7 
                  89.8    
                  73.7 
                  89.8  
                  73.7 
                  89.8  
               
               
                 Max 
                 512   
                 651     
                 512   
                 651    
                 512   
                 651    
               
               
                 n (Patient) 
                  61   
                  23     
                  68   
                  16    
                  69   
                  15    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 235   
                 307     
                 243   
                 307    
                 245   
                 312    
               
               
                 Average 
                 252   
                 324     
                 254   
                 325    
                 255   
                 327    
               
               
                 Stdev 
                 114   
                 154     
                 113   
                 166    
                 112   
                 174    
               
               
                 p (t-test) 
                   
                   0.047  
                   
                   0.068 
                   
                   0.073 
               
               
                 Min 
                  73.7 
                  89.8    
                  73.7 
                  89.8  
                  73.7 
                  89.8  
               
               
                 Max 
                 651   
                 592     
                 651   
                 592    
                 651   
                 592    
               
               
                 n (Patient) 
                  67   
                  14     
                  69   
                  12    
                  70   
                  11    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 233   
                 302     
                 235   
                 350    
                 235   
                 350    
               
               
                 Average 
                 248   
                 346     
                 252   
                 388    
                 252   
                 388    
               
               
                 Stdev 
                 110   
                 147     
                 111   
                 155    
                 111   
                 155    
               
               
                 p (t-test) 
                   
                   0.0037 
                   
                 9.9E−4 
                   
                 9.9E−4 
               
               
                 Min 
                  73.7 
                 161     
                  73.7 
                 177    
                  73.7 
                 177    
               
               
                 Max 
                 590   
                 651     
                 590   
                 651    
                 590   
                 651    
               
               
                 n (Patient) 
                  60   
                  17     
                  67   
                  10    
                  67   
                  10    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 UO only 
                 sCr only 
                 sCr or UO 
                 UO only 
                 sCr only 
                 sCr or UO 
                 UO only 
                 sCr only 
               
               
                   
               
               
                 AUC 
                 0.63 
                 0.64 
                 0.70 
                 0.65 
                 0.62 
                 0.77 
                 0.64 
                 0.61 
                 0.77 
               
               
                 SE 
                 0.071 
                 0.086 
                 0.077 
                 0.081 
                 0.093 
                 0.091 
                 0.083 
                 0.096 
                 0.091 
               
               
                 p Value 
                 0.064 
                 0.10 
                 0.0081 
                 0.066 
                 0.20 
                 0.0030 
                 0.085 
                 0.25 
                 0.0030 
               
               
                 nCohort  
                 61 
                 67 
                 60 
                 68 
                 69 
                 67 
                 69 
                 70 
                 67 
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 23 
                 14 
                 17 
                 16 
                 12 
                 10 
                 15 
                 11 
                 10 
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 87% 
                 86% 
                 88% 
                 88% 
                 83% 
                 100% 
                 87% 
                 82% 
                 100% 
               
               
                 Specificity 
                 30% 
                 27% 
                 28% 
                 28% 
                 26% 
                  28% 
                 28% 
                 26% 
                  28% 
               
               
                 Cutoff  
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 70% 
                 71% 
                 76% 
                 75% 
                 67% 
                  90% 
                 73% 
                 64% 
                  90% 
               
               
                 Specificity 
                 57% 
                 54% 
                 57% 
                 56% 
                 52% 
                  55% 
                 55% 
                 51% 
                  55% 
               
               
                 Cutoff  
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 30% 
                 36% 
                 41% 
                 31% 
                 33% 
                  50% 
                 33% 
                 36% 
                  50% 
               
               
                 Specificity 
                 77% 
                 76% 
                 78% 
                 76% 
                 75% 
                  78% 
                 77% 
                 76% 
                  78% 
               
               
                 OR  
                 2.79 
                 2.20 
                 2.97 
                 2.71 
                 1.76 
                 8.44 
                 2.47 
                 1.56 
                 8.44 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.13 
                 0.33 
                 0.18 
                 0.21 
                 0.49 
                 0.15 
                 0.26 
                 0.59 
                 0.15 
               
               
                 Lower limit  
                 0.736 
                 0.449 
                 0.612 
                 0.563 
                 0.353 
                 0.471 
                 0.509 
                 0.307 
                 0.471 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 10.6 
                 10.8 
                 14.4 
                 13.1 
                 8.83 
                 151 
                 12.0 
                 7.90 
                 151 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 3.08 
                 2.90 
                 4.25 
                 3.80 
                 2.18 
                 11.1 
                 3.37 
                 1.85 
                 11.1 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.031 
                 0.096 
                 0.021 
                 0.033 
                 0.24 
                 0.026 
                 0.055 
                 0.36 
                 0.026 
               
               
                 Lower limit  
                 1.11 
                 0.828 
                 1.24 
                 1.11 
                 0.601 
                 1.33 
                 0.977 
                 0.498 
                 1.33 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 8.56 
                 10.2 
                 14.6 
                 13.0 
                 7.92 
                 92.6 
                 11.6 
                 6.90 
                 92.6 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 1.47 
                 1.77 
                 2.53 
                 1.48 
                 1.53 
                 3.47 
                 1.66 
                 1.78 
                 3.47 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.48 
                 0.36 
                 0.11 
                 0.52 
                 0.53 
                 0.075 
                 0.41 
                 0.40 
                 0.075 
               
               
                 Lower limit  
                 0.504 
                 0.518 
                 0.806 
                 0.447 
                 0.409 
                 0.884 
                 0.494 
                 0.464 
                 0.884 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 4.28 
                 6.05 
                 7.95 
                 4.89 
                 5.72 
                 13.6 
                 5.56 
                 6.83 
                 13.6 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC)  
               
               
                 in EDTA samples for the “persistent” and “non-persistent” cohorts  
               
               
                 where persistence starts within 48 hours after sample collection and renal status 
               
               
                 is assessed by serum creatinine (sCr) only, urine output (UO) only,  
               
               
                 or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 226   
                 293    
                 231   
                 302    
                 233   
                 298    
               
               
                 Average 
                 245   
                 317    
                 247   
                 339    
                 248   
                 341    
               
               
                 Stdev 
                 110   
                 145    
                 107   
                 162    
                 107   
                 167    
               
               
                 p (t-test) 
                   
                   0.016 
                   
                   0.0061 
                   
                   0.0065 
               
               
                 Min 
                  73.7 
                  89.8   
                  73.7 
                  89.8   
                  73.7 
                  89.8   
               
               
                 Max 
                 512   
                 651    
                 512   
                 651    
                 512   
                 651    
               
               
                 n (Patient) 
                  60   
                  24    
                  67   
                  17    
                  68   
                  16    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 235   
                 307    
                 243   
                 307    
                 245   
                 312    
               
               
                 Average 
                 252   
                 324    
                 254   
                 325    
                 255   
                 327    
               
               
                 Stdev 
                 114   
                 154    
                 113   
                 166    
                 112   
                 174    
               
               
                 p (t-test) 
                   
                   0.047 
                   
                   0.068  
                   
                   0.073  
               
               
                 Min 
                  73.7 
                  89.8   
                  73.7 
                  89.8   
                  73.7 
                  89.8   
               
               
                 Max 
                 651   
                 592    
                 651   
                 592    
                 651   
                 592    
               
               
                 n (Patient) 
                  67   
                  14    
                  69   
                  12    
                  70   
                  11    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 226   
                 312 
                 231   
                 396    
                 231   
                 396    
               
               
                 Average 
                 239   
                 362 
                 244   
                 406    
                 244   
                 406    
               
               
                 Stdev 
                 100   
                 150 
                 102   
                 152    
                 102   
                 152    
               
               
                 p (t-test) 
                   
                 1.2E−4 
                   
                 1.5E−5 
                   
                 1.5E−5 
               
               
                 Min 
                  73.7 
                 161 
                  73.7 
                 177    
                 73.7 
                 177    
               
               
                 Max 
                 493   
                 651 
                 512   
                 651    
                 512   
                 651    
               
               
                 n (Patient) 
                  58   
                  19 
                  65   
                  12    
                 65   
                  12    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.65 
                 0.64 
                 0.75 
                 0.67 
                 0.62 
                 0.81 
                 0.66 
                 0.61 
                 0.81 
               
               
                 SE 
                 0.069 
                 0.086 
                 0.071 
                 0.078 
                 0.093 
                 0.078 
                 0.080 
                 0.096 
                 0.078 
               
               
                 p Value 
                 0.032 
                 0.10 
                 4.7E−4 
                 0.031 
                 0.20 
                 5.8E−5 
                 0.041 
                 0.25 
                 5.8E−5 
               
               
                 nCohort  
                 60 
                 67 
                 58 
                 67 
                 69 
                 65 
                 68 
                 70 
                 65 
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 24 
                 14 
                 19 
                 17 
                 12 
                 12 
                 16 
                 11 
                 12 
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 88% 
                 86% 
                 89% 
                 88% 
                 83% 
                 100% 
                 88% 
                 82% 
                 100% 
               
               
                 Specificity 
                 30% 
                 27% 
                 29% 
                 28% 
                 26% 
                  29% 
                 28% 
                 26% 
                  29% 
               
               
                 Cutoff  
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 71% 
                 71% 
                 79% 
                 76% 
                 67% 
                  92% 
                 75% 
                 64% 
                  92% 
               
               
                 Specificity 
                 58% 
                 54% 
                 59% 
                 57% 
                 52% 
                  57% 
                 56% 
                 51% 
                  57% 
               
               
                 Cutoff  
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 33% 
                 36% 
                 47% 
                 35% 
                 33% 
                  58% 
                 38% 
                 36% 
                  58% 
               
               
                 Specificity 
                 78% 
                 76% 
                 81% 
                 78% 
                 75% 
                  80% 
                 78% 
                 76% 
                  80% 
               
               
                 OR  
                 3.00 
                 2.20 
                 3.52 
                 2.97 
                 1.76 
                 10.5 
                 2.71 
                 1.56 
                 10.5 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.11 
                 0.33 
                 0.12 
                 0.17 
                 0.49 
                 0.11 
                 0.21 
                 0.59 
                 0.11 
               
               
                 Lower limit  
                 0.794 
                 0.449 
                 0.733 
                 0.619 
                 0.353 
                 0.591 
                 0.563 
                 0.307 
                 0.591 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 11.3 
                 10.8 
                 16.9 
                 14.2 
                 8.83 
                 186 
                 13.1 
                 7.90 
                 186 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 3.40 
                 2.90 
                 5.31 
                 4.26 
                 2.18 
                 14.5 
                 3.80 
                 1.85 
                 14.5 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.019 
                 0.096 
                 0.0073 
                 0.020 
                 0.24 
                 0.013 
                 0.033 
                 0.36 
                 0.013 
               
               
                 Lower limit  
                 1.23 
                 0.828 
                 1.57 
                 1.26 
                 0.601 
                 1.77 
                 1.11 
                 0.498 
                 1.77 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 9.42 
                 10.2 
                 18.0 
                 14.4 
                 7.92 
                 119 
                 13.0 
                 6.90 
                 119 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 1.81 
                 1.77 
                 3.85 
                 1.89 
                 1.53 
                 5.60 
                 2.12 
                 1.78 
                 5.60 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.27 
                 0.36 
                 0.018 
                 0.28 
                 0.53 
                 0.0093 
                 0.21 
                 0.40 
                 0.0093 
               
               
                 Lower limit  
                 0.634 
                 0.518 
                 1.26 
                 0.600 
                 0.409 
                 1.53 
                 0.662 
                 0.464 
                 1.53 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 5.15 
                 6.05 
                 11.7 
                 5.96 
                 5.72 
                 20.5 
                 6.78 
                 6.83 
                 20.5 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 221   
                 285    
                 233   
                 293    
                 235   
                 285    
               
               
                 Average 
                 245   
                 315    
                 248   
                 333    
                 249   
                 334    
               
               
                 Stdev 
                 111   
                 143    
                 108   
                 160    
                 107   
                 164    
               
               
                 p (t-test) 
                   
                   0.017 
                   
                   0.0097 
                   
                   0.010 
               
               
                 Min 
                  73.7 
                  89.8   
                  73.7 
                  89.8    
                  73.7 
                  89.8   
               
               
                 Max 
                 512   
                 651    
                 512   
                 651    
                 512   
                 651    
               
               
                 n (Patient) 
                  59   
                  25    
                  66   
                  18    
                  67   
                  17    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 233   
                 302    
                 243   
                 307    
                 245   
                 312    
               
               
                 Average 
                 252   
                 321    
                 254   
                 325    
                 255   
                 327    
               
               
                 Stdev 
                 114   
                 149    
                 113   
                 166    
                 112   
                 174    
               
               
                 p (t-test) 
                   
                   0.050 
                   
                   0.068  
                   
                   0.073 
               
               
                 Min 
                  73.7 
                  89.8   
                   
                  89.8    
                  73.7 
                  89.8   
               
               
                 Max 
                 651   
                 592    
                 651   
                 592    
                 651   
                 592    
               
               
                 n (Patient) 
                  66   
                  15    
                  69   
                  12    
                  70   
                  11    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 221   
                 307    
                 231   
                 350    
                 233   
                 389    
               
               
                 Average 
                 239   
                 358    
                 244   
                 384    
                 245   
                 392    
               
               
                 Stdev 
                 101   
                 147    
                 104   
                 151    
                 103   
                 154    
               
               
                 p (t-test) 
                   
                 1.5E−4 
                   
                 8.3E−5 
                   
                 5.2E−5 
               
               
                 Min 
                  73.7 
                 161    
                  73.7 
                 177    
                  73.7 
                 177    
               
               
                 Max 
                 493   
                 651    
                 512   
                 651    
                 512   
                 651    
               
               
                 n (Patient) 
                  57   
                  20    
                  63   
                  14    
                  64   
                  13    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.65  
                  0.64  
                  0.74  
                  0.66  
                  0.62  
                  0.78 
                  0.65  
                  0.61  
                  0.79  
               
               
                 SE 
                  0.068 
                  0.084 
                  0.069  
                  0.077 
                  0.093 
                  0.077 
                  0.079 
                  0.096 
                  0.079 
               
               
                 p Value 
                  0.028 
                  0.098 
                 4.4E−4 
                  0.040 
                  0.20  
                 3.3E−4 
                  0.053 
                  0.25  
                 2.7E−4 
               
               
                 nCohort  
                  59    
                  66    
                  57    
                  66    
                  69    
                 63    
                  67    
                 70    
                  64    
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                  25 
                  15    
                  20    
                  18    
                  12    
                 14    
                  17    
                  11    
                  13    
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 169    
                 171    
                 174    
                 169    
                 171    
                 174    
                 169    
                 171    
                 174    
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                  88% 
                 87% 
                 90% 
                 89% 
                 83% 
                 100% 
                 88% 
                 82% 
                 100% 
               
               
                 Specificity 
                  31% 
                 27% 
                 30% 
                 29% 
                 26% 
                  30% 
                 28% 
                 26% 
                  30% 
               
               
                 Cutoff  
                 249    
                 249    
                 249    
                 249 
                 249    
                 249    
                 249    
                 249    
                 249    
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                  72% 
                 73% 
                 80% 
                 72% 
                 67% 
                  86% 
                 71% 
                 64% 
                  85% 
               
               
                 Specificity 
                  59% 
                 55% 
                 60% 
                 56% 
                 52% 
                  57% 
                 55% 
                 51% 
                  56% 
               
               
                 Cutoff  
                 332    
                 331    
                 335    
                 332    
                 331    
                 335    
                 332    
                 331    
                 335    
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 32% 
                 33% 
                 45% 
                 33% 
                 33% 
                  50% 
                 35% 
                 36% 
                  54% 
               
               
                 Specificity 
                 78% 
                 76% 
                 81% 
                 77% 
                 75% 
                  79% 
                 78% 
                 76% 
                  80% 
               
               
                 OR Quartile 2 
                  3.22  
                  2.44  
                  3.82  
                  3.23  
                  1.76  
                 12.7 
                  2.97  
                  1.56 
                  11.6  
               
               
                 p Value 
                  0.084 
                  0.27  
                  0.093  
                  0.14  
                  0.49  
                  0.082 
                  0.17  
                  0.59 
                  0.095 
               
               
                 Lower limit  
                  0.854 
                  0.500 
                  0.798  
                  0.677 
                  0.353 
                  0.721 
                  0.619 
                  0.307 
                  0.655 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  12.1   
                  11.9   
                 18.3    
                  15.4  
                  8.83  
                 224    
                  14.2  
                   7.90  
                 205    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                  3.75  
                  3.30  
                  5.91  
                  3.32  
                  2.18  
                  8.00 
                  2.96  
                  1.85  
                  7.07  
               
               
                 p Value 
                  0.011 
                  0.060 
                  0.0042 
                  0.039 
                  0.24  
                  0.0098 
                  0.064 
                  0.36  
                  0.016 
               
               
                 Lower limit  
                  1.36  
                  0.952 
                  1.75  
                  1.06  
                  0.601 
                  1.65 
                  0.938 
                  0.498 
                  1.45  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit 
                  10.4  
                  11.4  
                  20.0   
                  10.4  
                  7.92  
                 38.8 
                  9.34  
                  6.90  
                  34.5  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                  1.67  
                  1.56  
                  3.42  
                  1.70  
                  1.53  
                  3.85 
                  1.89  
                  1.78  
                  4.58  
               
               
                 p Value 
                  0.34  
                  0.47  
                  0.028  
                  0.36  
                  0.53  
                  0.029 
                  0.28  
                  0.40  
                  0.017 
               
               
                 Lower limit  
                  0.588 
                  0.465 
                  1.14  
                  0.546 
                  0.409 
                  1.14 
                  0.600 
                  0.464 
                  1.31  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  4.72  
                  5.25  
                  10.3   
                  5.30  
                  5.72  
                 12.9 
                  5.96  
                  6.83  
                 16.0  
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC)  
               
               
                 in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status 
               
               
                 is assessed by serum creatinine (sCr) only, urine output (UO) 
               
               
                 only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 221 
                 285 
                 231 
                 285 
                 233 
                 283 
               
               
                 Average 
                 245 
                 315 
                 247 
                 330 
                 248 
                 331 
               
               
                 Stdev 
                 111 
                 143 
                 109 
                 155 
                 108 
                 160 
               
               
                 p (t-test) 
                   
                 0.017 
                   
                 0.010 
                   
                 0.011 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 512 
                 651 
                 512 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                 59 
                 25 
                 65 
                 19 
                 66 
                 18 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 233 
                 302 
                 239 
                 302 
                 243 
                 297 
               
               
                 Average 
                 252 
                 321 
                 254 
                 322 
                 255 
                 323 
               
               
                 Stdev 
                 114 
                 149 
                 114 
                 160 
                 113 
                 167 
               
               
                 p (t-test) 
                   
                 0.050 
                   
                 0.071 
                   
                 0.076 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 66 
                 15 
                 68 
                 13 
                 69 
                 12 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 221 
                 307 
                 226 
                 312 
                 231 
                 350 
               
               
                 Average 
                 239 
                 358 
                 244 
                 377 
                 244 
                 384 
               
               
                 Stdev 
                 101 
                 147 
                 105 
                 148 
                 104 
                 151 
               
               
                 p (t-test) 
                   
                 1.5E−4 
                   
                 1.2E−4 
                   
                 7.8E−5 
               
               
                 Min 
                 73.7 
                 161 
                 73.7 
                 177 
                 73.7 
                 177 
               
               
                 Max 
                 493 
                 651 
                 512 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                 57 
                 20 
                 62 
                 15 
                 63 
                 14 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.65 
                 0.64 
                 0.74 
                 0.66 
                 0.62 
                 0.77 
                 0.65 
                 0.61 
                 0.78 
               
               
                 SE 
                 0.068 
                 0.084 
                 0.069 
                 0.075 
                 0.089 
                 0.076 
                 0.077 
                 0.093 
                 0.077 
               
               
                 p Value 
                 0.028 
                 0.098 
                 4.4E−4 
                 0.035 
                 0.18 
                 3.2E−4 
                 0.047 
                 0.23 
                 2.8E−4 
               
               
                 nCohort  
                 59 
                 66 
                 57 
                 65 
                 68 
                 62 
                 66 
                 69 
                 63 
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 25 
                 15 
                 20 
                 19 
                 13 
                 15 
                 18 
                 12 
                 14 
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 88% 
                 87% 
                 90% 
                 89% 
                 85% 
                 100% 
                 89% 
                 83% 
                 100% 
               
               
                 Specificity 
                 31% 
                 27% 
                 30% 
                 29% 
                 26% 
                  31% 
                 29% 
                 26% 
                  30% 
               
               
                 Cutoff  
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 72% 
                 73% 
                 80% 
                 74% 
                 69% 
                  87% 
                 72% 
                 67% 
                  86% 
               
               
                 Specificity 
                 59% 
                 55% 
                 60% 
                 57% 
                 53% 
                  58% 
                 56% 
                 52% 
                  57% 
               
               
                 Cutoff  
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 32% 
                 33% 
                 45% 
                 32% 
                 31% 
                  47% 
                 33% 
                 33% 
                  50% 
               
               
                 Specificity 
                 78% 
                 76% 
                 81% 
                 77% 
                 75% 
                  79% 
                 77% 
                 75% 
                  79% 
               
               
                 OR  
                 3.22 
                 2.44 
                 3.82 
                 3.51 
                 1.98 
                 13.9 
                 3.23 
                 1.76 
                 12.7 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.084 
                 0.27 
                 0.093 
                 0.11 
                 0.40 
                 0.072 
                 0.14 
                 0.49 
                 0.082 
               
               
                 Lower limit 
                 0.854 
                 0.500 
                 0.798 
                 0.738 
                 0.400 
                 0.791 
                 0.677 
                 0.353 
                 0.721 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 12.1 
                 11.9 
                 18.3 
                 16.7 
                 9.81 
                 244 
                 15.4 
                 8.83 
                 224 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 3.75 
                 3.30 
                 5.91 
                 3.70 
                 2.53 
                 9.00 
                 3.32 
                 2.18 
                 8.00 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.011 
                 0.060 
                 0.0042 
                 0.024 
                 0.15 
                 0.0061 
                 0.039 
                 0.24 
                 0.0098 
               
               
                 Lower limit 
                 1.36 
                 0.952 
                 1.75 
                 1.19 
                 0.711 
                 1.87 
                 1.06 
                 0.601 
                 1.65 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 10.4 
                 11.4 
                 20.0 
                 11.5 
                 9.02 
                 43.3 
                 10.4 
                 7.92 
                 38.8 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 1.67 
                 1.56 
                 3.42 
                 1.54 
                 1.33 
                 3.30 
                 1.70 
                 1.53 
                 3.85 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.34 
                 0.47 
                 0.028 
                 0.45 
                 0.66 
                 0.048 
                 0.36 
                 0.53 
                 0.029 
               
               
                 Lower limit 
                 0.588 
                 0.465 
                 1.14 
                 0.499 
                 0.364 
                 1.01 
                 0.546 
                 0.409 
                 1.14 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 4.72 
                 5.25 
                 10.3 
                 4.75 
                 4.89 
                 10.8 
                 5.30 
                 5.72 
                 12.9 
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve  
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” 
               
               
                 cohorts where persistence starts within 168 hours after sample  
               
               
                 collection and renal status is assessed by serum creatinine (sCr) only,  
               
               
                 urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 219 
                 302 
                 226 
                 293 
                 233 
                 283 
               
               
                 Average 
                 237 
                 327 
                 241 
                 335 
                 246 
                 328 
               
               
                 Stdev 
                 104 
                 144 
                 102 
                 155 
                 107 
                 158 
               
               
                 p (t-test) 
                   
                 0.0016 
                   
                 0.0020 
                   
                 0.0099 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 493 
                 651 
                 493 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                 57 
                 27 
                 62 
                 22 
                 64 
                 20 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 233 
                 302 
                 239 
                 302 
                 243 
                 297 
               
               
                 Average 
                 252 
                 321 
                 254 
                 322 
                 255 
                 323 
               
               
                 Stdev 
                 114 
                 149 
                 114 
                 160 
                 113 
                 167 
               
               
                 p (t-test) 
                   
                 0.050 
                   
                 0.071 
                   
                 0.076 
               
               
                 Min 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
                 73.7 
                 89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                 66 
                 15 
                 68 
                 13 
                 69 
                 12 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 220 
                 302 
                 221 
                 298 
                 226 
                 312 
               
               
                 Average 
                 239 
                 352 
                 240 
                 366 
                 241 
                 371 
               
               
                 Stdev 
                 102 
                 146 
                 101 
                 150 
                 100 
                 153 
               
               
                 p (t-test) 
                   
                 2.3E−4 
                   
                 1.1E−4 
                   
                 8.4E−5 
               
               
                 Min 
                 73.7 
                 161 
                 73.7 
                 161 
                 73.7 
                 161 
               
               
                 Max 
                 493 
                 651 
                 493 
                 651 
                 493 
                 651 
               
               
                 n (Patient) 
                 56 
                 21 
                 59 
                 18 
                 60 
                 17 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.69 
                 0.64 
                 0.74 
                 0.68 
                 0.62 
                 0.75 
                 0.65 
                 0.61 
                 0.75 
               
               
                 SE 
                 0.065 
                 0.084 
                 0.069 
                 0.070 
                 0.089 
                 0.072 
                 0.074 
                 0.093 
                 0.073 
               
               
                 p Value 
                 0.0031 
                 0.098 
                 5.7E−4 
                 0.010 
                 0.18 
                 4.9E−4 
                 0.040 
                 0.23 
                 5.0E−4 
               
               
                 nCohort  
                 57 
                 66 
                 56 
                 62 
                 68 
                 59 
                 64 
                 69 
                 60 
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 27 
                 15 
                 21 
                 22 
                 13 
                 18 
                 20 
                 12 
                 17 
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 89% 
                 87% 
                 90% 
                 86% 
                 85% 
                 94% 
                 85% 
                 83% 
                 94% 
               
               
                 Specificity 
                 32% 
                 27% 
                 30% 
                 29% 
                 26% 
                 31% 
                 28% 
                 26% 
                 30% 
               
               
                 Cutoff  
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 74% 
                 73% 
                 81% 
                 73% 
                 69% 
                 83% 
                 70% 
                 67% 
                 82% 
               
               
                 Specificity 
                 61% 
                 55% 
                 61% 
                 58% 
                 53% 
                 59% 
                 56% 
                 52% 
                 58% 
               
               
                 Cutoff  
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 37% 
                 33% 
                 43% 
                 36% 
                 31% 
                 44% 
                 35% 
                 33% 
                 47% 
               
               
                 Specificity 
                 81% 
                 76% 
                 80% 
                 79% 
                 75% 
                 80% 
                 78% 
                 75% 
                 80% 
               
               
                 OR  
                 3.69 
                 2.44 
                 4.14 
                 2.59 
                 1.98 
                 7.46 
                 2.22 
                 1.76 
                 6.86 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.053 
                 0.27 
                 0.075 
                 0.16 
                 0.40 
                 0.060 
                 0.25 
                 0.49 
                 0.072 
               
               
                 Lower limit 
                 0.983 
                 0.500 
                 0.866 
                 0.682 
                 0.400 
                 0.922 
                 0.579 
                 0.353 
                 0.844 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 13.9 
                 11.9 
                 19.8 
                 9.85 
                 9.81 
                 60.4 
                 8.49 
                 8.83 
                 55.7 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 4.55 
                 3.30 
                 6.57 
                 3.69 
                 2.53 
                 7.29 
                 3.00 
                 2.18 
                 6.53 
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.0034 
                 0.060 
                 0.0024 
                 0.016 
                 0.15 
                 0.0038 
                 0.045 
                 0.24 
                 0.0064 
               
               
                 Lower limit 
                 1.65 
                 0.952 
                 1.95 
                 1.27 
                 0.711 
                 1.90 
                 1.02 
                 0.601 
                 1.70 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 12.5 
                 11.4 
                 22.1 
                 10.7 
                 9.02 
                 28.0 
                 8.80 
                 7.92 
                 25.2 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                 2.46 
                 1.56 
                 3.07 
                 2.15 
                 1.33 
                 3.13 
                 1.92 
                 1.53 
                 3.56 
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                 0.084 
                 0.47 
                 0.043 
                 0.16 
                 0.66 
                 0.047 
                 0.24 
                 0.53 
                 0.030 
               
               
                 Lower limit 
                 0.886 
                 0.465 
                 1.03 
                 0.744 
                 0.364 
                 1.02 
                 0.644 
                 0.409 
                 1.13 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 6.83 
                 5.25 
                 9.10 
                 6.23 
                 4.89 
                 9.65 
                 5.74 
                 5.72 
                 11.2 
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     Example 13. Use of C-C Motif Chemokine 14 for Evaluating Renal Status in Patients Admitted to the ICU: Persistent at RIFLE I or F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 14 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output. Two cohorts are defined to represent a “persistent” and a “non-persistent” population. “Persistent” indicates those patients whose minimum RIFLE stage during a period of 24, 48 or 72 hours is injury (I) or failure (F) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. “Non-persistent” indicates those patients who are not persistent at injury (I) or failure (F) and whose minimum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0) or risk of injury (R) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. If a patient dies after injury (I) or failure (F) or is placed on renal replacement therapy (RRT) at any time from sample collection to 24, 48, 72, 96 or 168 hours after sample collection, the patient is considered “persistent”. 
     The ability to distinguish the “persistent” and “non-persistent” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 13.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in  
               
               
                 urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample  
               
               
                 collection and renal status is assessed by serum creatinine (sCr)  
               
               
                 only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.672 
                 1.38 
                 0.731 
                 2.77 
                 0.731 
                 2.87 
               
               
                 Average 
                 1.36 
                 2.40 
                 1.38 
                 3.06 
                 1.38 
                 3.35 
               
               
                 Stdev 
                 1.75 
                 2.19 
                 1.62 
                 2.42 
                 1.59 
                 2.46 
               
               
                 p (t-test) 
                   
                 0.020 
                   
                 3.4E−4 
                   
                 5.0E−5 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.121 
                 0.194 
                 0.121 
                 0.349 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 38 
                 45 
                 56 
                 27 
                 60 
                 23 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.768 
                 2.77 
                 0.812 
                 2.25 
                 0.922 
                 2.20 
               
               
                 Average 
                 1.50 
                 3.13 
                 1.64 
                 3.02 
                 1.72 
                 2.96 
               
               
                 Stdev 
                 1.76 
                 2.40 
                 1.83 
                 2.53 
                 1.88 
                 2.59 
               
               
                 p (t-test) 
                   
                 0.0011 
                   
                 0.011 
                   
                 0.033 
               
               
                 Min 
                 0.121 
                 0.349 
                 0.121 
                 0.349 
                 0.121 
                 0.349 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 57 
                 23 
                 61 
                 19 
                 64 
                 16 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.790 
                 1.15 
                 0.790 
                 1.19 
                 0.790 
                 1.19 
               
               
                 Average 
                 1.72 
                 2.05 
                 1.68 
                 2.29 
                 1.64 
                 2.39 
               
               
                 Stdev 
                 2.05 
                 2.04 
                 1.95 
                 2.15 
                 1.92 
                 2.19 
               
               
                 p (t-test) 
                   
                 0.48 
                   
                 0.20 
                   
                 0.12 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 35 
                 43 
                 49 
                 29 
                 51 
                 27 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.66  
                  0.71  
                  0.56  
                  0.71  
                  0.67  
                  0.59  
                  0.74  
                  0.64  
                  0.60  
               
               
                 SE 
                  0.059  
                  0.067  
                 0.065 
                  0.064  
                  0.075 
                  0.068 
                  0.065 
                  0.081 
                  0.069 
               
               
                 p Value 
                  0.0074 
                 0.0015 
                  0.32  
                  0.0011 
                  0.027 
                  0.20  
                 2.3E−4 
                  0.078 
                  0.14  
               
               
                 nCohort  
                 38    
                 57    
                 35   
                 56    
                 61    
                 49    
                 60    
                 64   
                 51    
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 45    
                 23    
                 43   
                 27    
                 19    
                 29    
                 23    
                 16     
                 27    
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                  0.467  
                  0.457  
                  0.483 
                  0.467  
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                 0.483 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 82% 
                 87% 
                 79% 
                 85% 
                 84% 
                 79% 
                 87% 
                 81% 
                 81% 
               
               
                 Specificity 
                 34% 
                 30% 
                 31% 
                 30% 
                 28% 
                 29% 
                 30% 
                 27% 
                 29% 
               
               
                 Cutoff  
                  1.04  
                  1.04  
                  1.03  
                  1.04  
                  1.04  
                  1.03  
                  1.04  
                  1.04  
                  1.03  
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 60% 
                 70% 
                 53% 
                 67% 
                 63% 
                 55% 
                 70% 
                 62% 
                 56% 
               
               
                 Specificity 
                 61% 
                 58% 
                 54% 
                 57% 
                 54% 
                 53% 
                 57% 
                 53% 
                 53% 
               
               
                 Cutoff  
                  2.82  
                  2.88  
                  2.84  
                  2.82  
                  2.88  
                  2.84  
                  2.82  
                  2.88  
                  2.84  
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 38% 
                 43% 
                 30% 
                 48% 
                 37% 
                 34% 
                 52% 
                 31% 
                 37% 
               
               
                 Specificity 
                 89% 
                 82% 
                 80% 
                 86% 
                 79% 
                 80% 
                 85% 
                 77% 
                 80% 
               
               
                 OR  
                  2.40  
                  2.83  
                  1.73  
                  2.51  
                  2.06  
                  1.53  
                  2.86  
                  1.57  
                  1.83  
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.091  
                  0.13  
                  0.29  
                  0.14  
                  0.30  
                  0.44  
                  0.12  
                  0.52  
                  0.30  
               
               
                 Lower limit  
                  0.870  
                  0.742  
                 0.622 
                  0.751  
                  0.532 
                  0.515 
                  0.753 
                  0.397 
                  0.585 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  6.65  
                  10.8   
                  4.82  
                  8.36  
                  7.98  
                  4.57  
                 10.8  
                  6.18  
                  5.75  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  2.30  
                  3.14  
                  1.37  
                  2.67  
                  2.02  
                  1.39  
                  2.99  
                  1.89  
                  1.41  
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.064  
                  0.030  
                  0.50  
                  0.045  
                  0.19  
                  0.48  
                  0.036 
                  0.27  
                  0.48  
               
               
                 Lower limit  
                  0.952  
                  1.12  
                  0.558 
                  1.02  
                  0.700 
                  0.553 
                  1.07  
                  0.613 
                  0.551 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  5.56  
                  8.82  
                  3.34  
                  6.96  
                  5.83  
                  3.50  
                  8.33  
                  5.82  
                  3.59  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  5.16  
                  3.62  
                  1.73  
                  5.57  
                  2.15  
                  2.05  
                  6.18  
                  1.48  
                  2.41  
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.0073 
                  0.019  
                  0.31  
                  0.0015 
                  0.18  
                  0.17  
                 9.7E−4 
                  0.52  
                  0.098 
               
               
                 Lower limit  
                  1.56  
                  1.24  
                  0.605 
                  1.92  
                 0.706 
                  0.730 
                  2.09  
                  0.445 
                  0.850 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 17.1   
                 10.5   
                  4.97  
                 16.1  
                  6.57  
                  5.77  
                 18.2  
                  4.95  
                  6.84  
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.557 
                 1.20 
                 0.653 
                 2.16 
                 0.653 
                 2.25 
               
               
                 Average 
                 1.29 
                 2.29 
                 1.31 
                 2.86 
                 1.32 
                 3.06 
               
               
                 Stdev 
                 1.70 
                 2.17 
                 1.54 
                 2.40 
                 1.52 
                 2.45 
               
               
                 p (t-test) 
                   
                 0.033 
                   
                 5.7E−4 
                   
                 1.4E−4 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.121 
                 0.194 
                 0.121 
                 0.349 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 30 
                 53 
                 50 
                 33 
                 54 
                 29 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.665 
                 2.25 
                 0.922 
                 2.20 
                 0.922 
                 2.20 
               
               
                 Average 
                 1.50 
                 2.89 
                 1.63 
                 2.84 
                 1.70 
                 2.88 
               
               
                 Stdev 
                 1.79 
                 2.34 
                 1.85 
                 2.45 
                 1.89 
                 2.50 
               
               
                 p (t-test) 
                   
                 0.0040 
                   
                 0.020 
                   
                 0.034 
               
               
                 Min 
                 0.121 
                 0.349 
                 0.121 
                 0.349 
                 0.121 
                 0.349 
               
               
                 Max 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
                 7.86 
                 6.79 
               
               
                 n (Patient) 
                 53 
                 27 
                 58 
                 22 
                 62 
                 18 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
                 Non-persistent  
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.790 
                 1.15 
                 0.773 
                 1.28 
                 0.773 
                 1.59 
               
               
                 Average 
                 1.51 
                 2.14 
                 1.50 
                 2.43 
                 1.47 
                 2.52 
               
               
                 Stdev 
                 1.83 
                 2.13 
                 1.77 
                 2.26 
                 1.74 
                 2.29 
               
               
                 p (t-test) 
                   
                 0.19 
                   
                 0.046 
                   
                 0.024 
               
               
                 Min 
                 0.208 
                 0.121 
                 0.121 
                 0.194 
                 0.121 
                 0.194 
               
               
                 Max 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
                 7.86 
                 6.66 
               
               
                 n (Patient) 
                 29 
                 49 
                 44 
                 34 
                 46 
                 32 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.67   
                  0.70  
                  0.59  
                  0.71  
                  0.66  
                  0.62  
                  0.73  
                  0.65  
                  0.63  
               
               
                 SE 
                  0.060  
                  0.064  
                  0.066  
                  0.060  
                  0.071 
                  0.065 
                  0.061  
                  0.077 
                  0.065 
               
               
                 p Value 
                 0.0046 
                  0.0015 
                  0.15  
                 5.6E−4 
                  0.022 
                  0.060 
                 1.7E−4 
                  0.050 
                  0.038 
               
               
                 nCohort  
                 30    
                 53   
                 29   
                 50    
                 58    
                 44    
                 54    
                 62    
                 46    
               
               
                 Non- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 53    
                 27   
                 49   
                 33    
                 22    
                 34    
                 29    
                 18    
                 32    
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff  
                  0.467  
                  0.457  
                  0.483  
                  0.467  
                  0.457 
                  0.483 
                  0.467  
                  0.457 
                  0.483 
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 81% 
                 89% 
                 78% 
                 85% 
                 86% 
                 79% 
                 86% 
                 83% 
                 81% 
               
               
                 Specificity 
                 37% 
                 32% 
                 31% 
                 32% 
                 29% 
                 30% 
                 31% 
                 27% 
                 30% 
               
               
                 Cutoff  
                  1.04   
                  1.04  
                  1.03  
                  1.04  
                  1.04  
                  1.03  
                  1.04  
                  1.04  
                  1.03  
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 57% 
                 63% 
                 53% 
                 64% 
                 59% 
                 56% 
                 66% 
                 61% 
                 56% 
               
               
                 Specificity 
                 60% 
                 57% 
                 55% 
                 58% 
                 53% 
                 55% 
                 57% 
                 53% 
                 54% 
               
               
                 Cutoff  
                  2.82   
                  2.88  
                  2.84  
                  2.82  
                  2.88  
                  2.84  
                  2.82  
                  2.88  
                  2.84  
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Sensitivity 
                 34% 
                 41% 
                 31% 
                 42% 
                 36% 
                 35% 
                 45% 
                 33% 
                 38% 
               
               
                 Specificity 
                 90% 
                 83% 
                 83% 
                 86% 
                 79% 
                 82% 
                 85% 
                 77% 
                 83% 
               
               
                 OR  
                  2.49   
                  3.78  
                  1.55  
                  2.64  
                  2.63  
                  1.62  
                  2.87  
                  1.89  
                  1.90  
               
               
                 Quartile 2 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.077  
                  0.050  
                  0.40  
                  0.090  
                  0.16  
                  0.37  
                  0.085  
                  0.36  
                  0.25  
               
               
                 Lower limit  
                  0.905  
                  0.997  
                  0.553  
                  0.858  
                  0.686 
                  0.564 
                  0.864  
                  0.485 
                  0.639 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  6.85   
                 14.3   
                  4.37  
                  8.09  
                 10.1  
                  4.64  
                  9.55  
                  7.36  
                  5.62  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  1.96   
                  2.22  
                  1.39  
                  2.42  
                  1.66  
                  1.52  
                  2.56  
                  1.79  
                  1.53  
               
               
                 Quartile 3 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.15   
                  0.10  
                  0.48  
                  0.056  
                  0.32  
                  0.36  
                  0.049  
                  0.29  
                  0.36  
               
               
                 Lower limit  
                  0.787  
                  0.856  
                  0.553  
                  0.978  
                  0.614 
                 0.618 
                  1.00  
                  0.613 
                  0.617 
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  4.86   
                  5.74  
                  3.50  
                  5.97  
                  4.48  
                  3.74  
                  6.53  
                  5.22  
                  3.79  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR  
                  4.63   
                  3.36  
                  2.12  
                  4.53  
                  2.19  
                  2.45  
                  4.67  
                  1.71  
                  2.85  
               
               
                 Quartile 4 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 p Value 
                  0.023  
                  0.024  
                  0.20  
                  0.0051 
                  0.15  
                  0.091 
                  0.0040 
                  0.36  
                  0.050 
               
               
                 Lower limit  
                  1.23   
                  1.18  
                  0.678  
                  1.57  
                  0.747 
                  0.868 
                  1.64  
                 0.545 
                  1.00  
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                 17.4    
                  9.61  
                  6.62  
                 13.0   
                  6.43  
                  6.94  
                 13.3   
                  5.40  
                  8.11  
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.557 
                  1.19 
                  0.653 
                  1.99 
                  0.653 
                  2.16 
               
               
                 Average 
                  1.32 
                  2.25 
                  1.34 
                  2.73 
                  1.35 
                  2.90 
               
               
                 Stdev 
                  1.72 
                  2.16 
                  1.56 
                  2.39 
                  1.54 
                  2.45 
               
               
                 p (t-test) 
                   
                  0.049 
                   
                  0.0020 
                   
                  6.3E-4 
               
               
                 Min 
                  0.208 
                  0.121 
                  0.121 
                  0.194 
                  0.121 
                  0.349 
               
               
                 Max 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
               
               
                 n (Patient) 
                 29 
                 54 
                 48 
                 35 
                 52 
                 31 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.739 
                  2.20 
                  1.03 
                  2.16 
                  1.03 
                  2.16 
               
               
                 Average 
                  1.52 
                  2.80 
                  1.66 
                  2.74 
                  1.72 
                  2.75 
               
               
                 Stdev 
                  1.80 
                  2.35 
                  1.86 
                  2.45 
                  1.90 
                  2.49 
               
               
                 p (t-test) 
                   
                  0.0077 
                   
                  0.035 
                   
                  0.061 
               
               
                 Min 
                  0.121 
                  0.349 
                  0.121 
                  0.349 
                  0.121 
                  0.349 
               
               
                 Max 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
               
               
                 n (Patient) 
                 52 
                 28 
                 57 
                 23 
                 61 
                 19 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.790 
                  1.15 
                  0.790 
                  1.19 
                  0.790 
                  1.19 
               
               
                 Average 
                  1.51 
                  2.14 
                  1.52 
                  2.38 
                  1.49 
                  2.47 
               
               
                 Stdev 
                  1.83 
                  2.13 
                  1.79 
                  2.24 
                  1.76 
                  2.27 
               
               
                 p (t-test) 
                   
                  0.19 
                   
                  0.063 
                   
                  0.035 
               
               
                 Min 
                  0.208 
                  0.121 
                  0.121 
                  0.194 
                  0.121 
                  0.194 
               
               
                 Max 
                  7.86 
                  6.66 
                  7.86 
                  6.66 
                  7.86 
                  6.66 
               
               
                 n (Patient) 
                 29 
                 49 
                 43 
                 35 
                 45 
                 33 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.65 
                  0.68 
                  0.59 
                  0.68 
                  0.64 
                  0.62 
                  0.70 
                  0.62 
                  0.63 
               
               
                 SE 
                  0.061 
                  0.065 
                  0.066 
                  0.060 
                  0.071 
                  0.064 
                  0.061 
                  0.077 
                  0.065 
               
               
                 p Value 
                  0.012 
                  0.0048 
                  0.15 
                  0.0025 
                  0.051 
                  0.069 
                  0.0010 
                  0.11 
                  0.045 
               
               
                 nCohort Non-persistent 
                 29 
                 52 
                 29 
                 48 
                 57 
                 43 
                 52 
                 61 
                 45 
               
               
                 nCohort Persistent 
                 54 
                 28 
                 49 
                 35 
                 23 
                 35 
                 31 
                 19 
                 33 
               
               
                 Cutoff Quartile 2 
                  0.467 
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                  0.483 
               
               
                 Sensitivity 
                 80% 
                 86% 
                 78% 
                 83% 
                 83% 
                 80% 
                 84% 
                 79% 
                 82% 
               
               
                 Specificity 
                 34% 
                 31% 
                 31% 
                 31% 
                 28% 
                 30% 
                 31% 
                 26% 
                 31% 
               
               
                 Cutoff Quartile 3 
                  1.04 
                  1.04 
                  1.03 
                  1.04 
                  1.04 
                  1.03 
                  1.04 
                  1.04 
                  1.03 
               
               
                 Sensitivity 
                 56% 
                 61% 
                 53% 
                 60% 
                 57% 
                 54% 
                 61% 
                 58% 
                 55% 
               
               
                 Specificity 
                 59% 
                 56% 
                 55% 
                 56% 
                 53% 
                 53% 
                 56% 
                 52% 
                 53% 
               
               
                 Cutoff Quartile 4 
                  2.82 
                  2.88 
                  2.84 
                  2.82 
                  2.88 
                  2.84 
                  2.82 
                  2.88 
                  2.84 
               
               
                 Sensitivity 
                 33% 
                 39% 
                 31% 
                 40% 
                 35% 
                 34% 
                 42% 
                 32% 
                 36% 
               
               
                 Specificity 
                 90% 
                 83% 
                 83% 
                 85% 
                 79% 
                 81% 
                 85% 
                 77% 
                 82% 
               
               
                 OR Quartile 2 
                  2.06 
                  2.67 
                  1.55 
                  2.20 
                  1.85 
                  1.73 
                  2.31 
                  1.33 
                  2.03 
               
               
                 p Value 
                  0.16 
                  0.11 
                  0.40 
                  0.15 
                  0.32 
                  0.31 
                  0.14 
                  0.65 
                  0.20 
               
               
                 Lower limit of 95% CI 
                  0.748 
                  0.794 
                  0.553 
                  0.753 
                  0.545 
                  0.605 
                  0.751 
                  0.385 
                  0.686 
               
               
                 Upper limit of 95% CI 
                  5.66 
                  8.95 
                  4.37 
                  6.41 
                  6.30 
                  4.97 
                  7.11 
                  4.62 
                  6.02 
               
               
                 OR Quartile 3 
                  1.77 
                  1.95 
                  1.39 
                  1.93 
                  1.44 
                  1.37 
                  2.00 
                  1.52 
                  1.37 
               
               
                 p Value 
                  0.22 
                  0.16 
                  0.48 
                  0.15 
                  0.46 
                  0.50 
                  0.13 
                  0.43 
                  0.49 
               
               
                 Lower limit of 95% CI 
                  0.710 
                  0.765 
                  0.553 
                  0.796 
                  0.545 
                  0.558 
                  0.806 
                  0.536 
                  0.557 
               
               
                 Upper limit of 95% CI 
                  4.41 
                  4.96 
                  3.50 
                  4.67 
                  3.83 
                  3.34 
                  4.94 
                  4.29 
                  3.38 
               
               
                 OR Quartile 4 
                  4.33 
                  3.09 
                  2.12 
                  3.90 
                  2.00 
                  2.28 
                  3.97 
                  1.55 
                  2.64 
               
               
                 p Value 
                  0.030 
                  0.034 
                  0.20 
                  0.011 
                  0.20 
                  0.12 
                  0.0092 
                  0.45 
                  0.068 
               
               
                 Lower limit of 95% CI 
                  1.15 
                  1.09 
                  0.678 
                  1.37 
                  0.687 
                  0.809 
                  1.41 
                  0.497 
                  0.932 
               
               
                 Upper limit of 95% CI 
                 16.3 
                  8.79 
                  6.62 
                 11.1 
                  5.82 
                  6.44 
                 11.2 
                  4.83 
                  7.50 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.556 
                  1.19 
                  0.637 
                  1.68 
                  0.639 
                  1.99 
               
               
                 Average 
                  1.18 
                  2.29 
                  1.26 
                  2.72 
                  1.28 
                  2.81 
               
               
                 Stdev 
                  1.56 
                  2.18 
                  1.47 
                  2.37 
                  1.46 
                  2.42 
               
               
                 p (t-test) 
                   
                  0.021 
                   
                  9.7E−4 
                   
                  5.8E−4 
               
               
                 Min 
                  0.208 
                  0.121 
                  0.121 
                  0.194 
                  0.121 
                  0.349 
               
               
                 Max 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
               
               
                 n (Patient) 
                 27 
                 56 
                 45 
                 38 
                 48 
                 35 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.653 
                  2.20 
                  1.03 
                  2.16 
                  1.03 
                  2.07 
               
               
                 Average 
                  1.50 
                  2.74 
                  1.65 
                  2.67 
                  1.74 
                  2.58 
               
               
                 Stdev 
                  1.82 
                  2.29 
                  1.88 
                  2.38 
                  1.93 
                  2.39 
               
               
                 p (t-test) 
                   
                  0.0089 
                   
                  0.041 
                   
                  0.11 
               
               
                 Min 
                  0.121 
                  0.349 
                  0.121 
                  0.349 
                  0.121 
                  0.349 
               
               
                 Max 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
               
               
                 n (Patient) 
                 50 
                 30 
                 55 
                 25 
                 58 
                 22 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.640 
                  1.15 
                  0.665 
                  1.19 
                  0.727 
                  1.16 
               
               
                 Average 
                  1.38 
                  2.18 
                  1.46 
                  2.35 
                  1.45 
                  2.38 
               
               
                 Stdev 
                  1.70 
                  2.16 
                  1.74 
                  2.23 
                  1.72 
                  2.25 
               
               
                 p (t-test) 
                   
                  0.097 
                   
                  0.052 
                   
                  0.044 
               
               
                 Min 
                  0.208 
                  0.121 
                  0.121 
                  0.194 
                  0.121 
                  0.194 
               
               
                 Max 
                  7.86 
                  6.66 
                  7.86 
                  6.66 
                  7.86 
                  6.66 
               
               
                 n (Patient) 
                 27 
                 51 
                 39 
                 39 
                 40 
                 38 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.68 
                  0.69 
                  0.62 
                  0.70 
                  0.65 
                  0.63 
                  0.71 
                  0.62 
                  0.63 
               
               
                 SE 
                  0.060 
                  0.063 
                  0.065 
                  0.058 
                  0.069 
                  0.063 
                  0.059 
                  0.073 
                  0.063 
               
               
                 p Value 
                  0.0029 
                  0.0025 
                  0.072 
                  5.5E−4 
                  0.033 
                  0.034 
                  3.8E−4 
                  0.10 
                  0.044 
               
               
                 nCohort Non-persistent 
                 27 
                 50 
                 27 
                 45 
                 55 
                 39 
                 48 
                 58 
                 40 
               
               
                 nCohort Persistent 
                 56 
                 30 
                 51 
                 38 
                 25 
                 39 
                 35 
                 22 
                 38 
               
               
                 Cutoff Quartile 2 
                  0.467 
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                  0.483 
               
               
                 Sensitivity 
                 80% 
                 87% 
                 78% 
                 84% 
                 84% 
                 82% 
                 86% 
                 82% 
                 82% 
               
               
                 Specificity 
                 37% 
                 32% 
                 33% 
                 33% 
                 29% 
                 33% 
                 33% 
                 28% 
                 32% 
               
               
                 Cutoff Quartile 3 
                  1.04 
                  1.04 
                  1.03 
                  1.04 
                  1.04 
                  1.03 
                  1.04 
                  1.04 
                  1.03 
               
               
                 Sensitivity 
                 55% 
                 60% 
                 53% 
                 61% 
                 56% 
                 54% 
                 60% 
                 55% 
                 53% 
               
               
                 Specificity 
                 59% 
                 56% 
                 56% 
                 58% 
                 53% 
                 54% 
                 56% 
                 52% 
                 52% 
               
               
                 Cutoff Quartile 4 
                  2.82 
                  2.88 
                  2.84 
                  2.82 
                  2.88 
                  2.84 
                  2.82 
                  2.88 
                  2.84 
               
               
                 Sensitivity 
                 34% 
                 40% 
                 31% 
                 39% 
                 36% 
                 33% 
                 40% 
                 32% 
                 34% 
               
               
                 Specificity 
                 93% 
                 84% 
                 85% 
                 87% 
                 80% 
                 82% 
                 85% 
                 78% 
                 82% 
               
               
                 OR Quartile 2 
                  2.41 
                  3.06 
                  1.82 
                  2.67 
                  2.15 
                  2.29 
                  3.00 
                  1.71 
                  2.13 
               
               
                 p Value 
                  0.092 
                  0.070 
                  0.26 
                  0.072 
                  0.22 
                  0.12 
                  0.055 
                  0.39 
                  0.16 
               
               
                 Lower limit of 95% CI 
                  0.866 
                  0.913 
                  0.641 
                  0.915 
                  0.638 
                  0.796 
                  0.978 
                  0.503 
                  0.743 
               
               
                 Upper limit of 95% CI 
                  6.69 
                  10.2 
                  5.15 
                  7.77 
                  7.28 
                  6.56 
                  9.20 
                  5.85 
                  6.12 
               
               
                 OR Quartile 3 
                  1.80 
                  1.91 
                  1.41 
                  2.10 
                  1.42 
                  1.36 
                  1.93 
                  1.29 
                  1.23 
               
               
                 p Value 
                  0.21 
                  0.17 
                  0.48 
                  0.099 
                  0.47 
                  0.50 
                  0.15 
                  0.62 
                  0.65 
               
               
                 Lower limit of 95% CI 
                  0.711 
                  0.761 
                  0.551 
                  0.871 
                  0.549 
                  0.559 
                  0.796 
                  0.480 
                  0.505 
               
               
                 Upper limit of 95% CI 
                  4.58 
                  4.79 
                  3.59 
                  5.05 
                  3.67 
                  3.32 
                  4.67 
                  3.44 
                  2.99 
               
               
                 OR Quartile 4 
                  6.42 
                  3.50 
                  2.63 
                  4.24 
                  2.25 
                  2.29 
                  3.90 
                  1.62 
                  2.45 
               
               
                 p Value 
                  0.018 
                  0.020 
                  0.12 
                  0.0086 
                  0.13 
                  0.12 
                  0.011 
                  0.39 
                  0.096 
               
               
                 Lower limit of 95% CI 
                  1.37 
                  1.22 
                  0.780 
                  1.44 
                  0.787 
                  0.796 
                  1.37 
                  0.544 
                  0.853 
               
               
                 Upper limit of 95% CI 
                 30.0 
                 10.0 
                  8.86 
                 12.5 
                  6.43 
                  6.56 
                 11.1 
                  4.80 
                  7.04 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.556 
                  1.19 
                  0.637 
                  1.68 
                  0.639 
                  1.99 
               
               
                 Average 
                  1.14 
                  2.27 
                  1.24 
                  2.66 
                  1.27 
                  2.75 
               
               
                 Stdev 
                  1.57 
                  2.16 
                  1.47 
                  2.35 
                  1.46 
                  2.40 
               
               
                 p (t-test) 
                   
                  0.021 
                   
                  0.0013 
                   
                  8.6E−4 
               
               
                 Min 
                  0.208 
                  0.121 
                  0.208 
                  0.121 
                  0.194 
                  0.121 
               
               
                 Max 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
               
               
                 n (Patient) 
                 25 
                 58 
                 43 
                 40 
                 46 
                 37 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.640 
                  2.25 
                  0.911 
                  2.20 
                  0.911 
                  2.20 
               
               
                 Average 
                  1.41 
                  2.84 
                  1.57 
                  2.79 
                  1.59 
                  2.85 
               
               
                 Stdev 
                  1.73 
                  2.32 
                  1.81 
                  2.40 
                  1.80 
                  2.46 
               
               
                 p (t-test) 
                   
                  0.0024 
                   
                  0.014 
                   
                  0.012 
               
               
                 Min 
                  0.121 
                  0.349 
                  0.121 
                  0.349 
                  0.121 
                  0.349 
               
               
                 Max 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
                  7.86 
                  6.79 
               
               
                 n (Patient) 
                 49 
                 31 
                 54 
                 26 
                 56 
                 24 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.715 
                  1.14 
                  0.790 
                  1.14 
                  0.790 
                  1.14 
               
               
                 Average 
                  1.42 
                  2.15 
                  1.52 
                  2.25 
                  1.49 
                  2.32 
               
               
                 Stdev 
                  1.72 
                  2.15 
                  1.77 
                  2.22 
                  1.73 
                  2.25 
               
               
                 p (t-test) 
                   
                  0.14 
                   
                  0.12 
                   
                  0.071 
               
               
                 Min 
                  0.208 
                  0.121 
                  0.208 
                  0.121 
                  0.208 
                  0.121 
               
               
                 Max 
                  7.86 
                  6.66 
                  7.86 
                  6.66 
                  7.86 
                  6.66 
               
               
                 n (Patient) 
                 26 
                 52 
                 37 
                 41 
                 39 
                 39 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                   0.68 
                  0.71 
                  0.60 
                  0.69 
                  0.67 
                  0.59 
                  0.70 
                  0.66 
                  0.60 
               
               
                 SE 
                   0.061 
                  0.061 
                  0.067 
                  0.058 
                  0.067 
                  0.064 
                  0.059 
                  0.069 
                  0.064 
               
               
                 p Value 
                   0.0027 
                  6.8E−4 
                  0.14 
                  0.0012 
                  0.014 
                  0.16 
                  8.9E−4 
                  0.021 
                  0.11 
               
               
                 nCohort Non-persistent 
                  25 
                 49 
                 26 
                 43 
                 54 
                 37 
                 46 
                 56 
                 39 
               
               
                 nCohort Persistent 
                  58 
                 31 
                 52 
                 40 
                 26 
                 41 
                 37 
                 24 
                 39 
               
               
                 Cutoff Quartile 2 
                   0.467 
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                  0.483 
                  0.467 
                  0.457 
                  0.483 
               
               
                 Sensitivity 
                 79% 
                 87% 
                 77% 
                 82% 
                 85% 
                 78% 
                 84% 
                 83% 
                 79% 
               
               
                 Specificity 
                 36% 
                 33% 
                 31% 
                 33% 
                 30% 
                 30% 
                 33% 
                 29% 
                 31% 
               
               
                 Cutoff Quartile 3 
                   1.04 
                  1.04 
                  1.03 
                  1.04 
                  1.04 
                  1.03 
                  1.04 
                  1.04 
                  1.03 
               
               
                 Sensitivity 
                 55% 
                 61% 
                 52% 
                 60% 
                 58% 
                 51% 
                 59% 
                 58% 
                 51% 
               
               
                 Specificity 
                 60% 
                 57% 
                 54% 
                 58% 
                 54% 
                 51% 
                 57% 
                 54% 
                 51% 
               
               
                 Cutoff Quartile 4 
                  2.82 
                  2.88 
                  2.84 
                  2.82 
                  2.88 
                  2.84 
                  2.82 
                  2.88 
                  2.84 
               
               
                 Sensitivity 
                 34% 
                 42% 
                  31% 
                 40% 
                 38% 
                 32% 
                 41% 
                 38% 
                 33% 
               
               
                 Specificity 
                 96% 
                 86% 
                  85% 
                 88% 
                 81% 
                 81% 
                 87% 
                 80% 
                 82% 
               
               
                 OR Quartile 2 
                  2.16 
                  3.27 
                  1.48 
                  2.28 
                  2.32 
                  1.50 
                  2.50 
                  2.00 
                  1.72 
               
               
                 p Value 
                  0.15 
                  0.054 
                  0.46 
                  0.12 
                  0.18 
                  0.43 
                  0.093 
                  0.27 
                  0.30 
               
               
                 Lower limit of 95% CI 
                  0.766 
                  0.978 
                  0.517 
                  0.808 
                  0.687 
                  0.542 
                  0.858 
                  0.590 
                  0.613 
               
               
                 Upper limit of 95% CI 
                  6.07 
                  11.0 
                  4.25 
                  6.41 
                  7.80 
                  4.18 
                  7.29 
                  6.77 
                  4.84 
               
               
                 OR Quartile 3 
                  1.85 
                  2.11 
                  1.26 
                  2.08 
                  1.58 
                  1.11 
                  1.91 
                  1.62 
                  1.11 
               
               
                 p Value 
                  0.21 
                  0.11 
                  0.63 
                  0.10 
                  0.34 
                  0.82 
                  0.15 
                  0.33 
                  0.82 
               
               
                 Lower limit of 95% CI 
                  0.712 
                  0.843 
                  0.490 
                  0.868 
                  0.615 
                  0.456 
                  0.793 
                  0.614 
                  0.456 
               
               
                 Upper limit of 95% CI 
                  4.79 
                  5.29 
                  3.24 
                  5.00 
                  4.07 
                  2.70 
                  4.59 
                  4.25 
                  2.69 
               
               
                 OR Quartile 4 
                  12.6 
                  4.33 
                  2.44 
                  5.07 
                  2.75 
                  1.99 
                  4.55 
                  2.45 
                  2.29 
               
               
                 p Value 
                  0.016 
                  0.0073 
                  0.15 
                  0.0048 
                  0.058 
                  0.20 
                  0.0060 
                  0.096 
                  0.12 
               
               
                 Lower limit of 95% CI 
                  1.59 
                  1.48 
                  0.724 
                  1.64 
                  0.965 
                  0.694 
                  1.54 
                  0.853 
                  0.796 
               
               
                 Upper limit of 95% CI 
                 100 
                 12.7 
                  8.26 
                 15.6 
                  7.83 
                  5.71 
                 13.4 
                  7.06 
                  6.56 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 219 
                 302 
                 220 
                 302 
                 224 
                 302 
               
               
                 Average 
                 224 
                 306 
                 236 
                 326 
                 242 
                 330 
               
               
                 Stdev 
                  86.6 
                 142 
                 94.4 
                 155 
                 101 
                 157 
               
               
                 p (t-test) 
                   
                  0.0024 
                   
                  0.0013 
                   
                  0.0033 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 434 
                 651 
                 446 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                  41 
                  43 
                  56 
                  28 
                  61 
                  23 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 226 
                 312 
                 235 
                 307 
                 243 
                 307 
               
               
                 Average 
                 242 
                 322 
                 248 
                 317 
                 251 
                 313 
               
               
                 Stdev 
                 111 
                 136 
                 112 
                 145 
                 112 
                 151 
               
               
                 p (t-test) 
                   
                  0.0085 
                   
                  0.030 
                   
                  0.061 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                  58 
                  23 
                  61 
                  20 
                  63 
                  18 
               
            
           
           
               
            
               
                 UO only 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 243 
                 252 
                 235 
                 257 
                 235 
                 257 
               
               
                 Average 
                 254 
                 284 
                 252 
                 301 
                 256 
                 297 
               
               
                 Stdev 
                 107 
                 140 
                 106 
                 150 
                 110 
                 148 
               
               
                 p (t-test) 
                   
                  0.28 
                   
                  0.098 
                   
                  0.17 
               
               
                 Min 
                 108 
                  73.7 
                  73.7 
                 105 
                  73.7 
                 105 
               
               
                 Max 
                 590 
                 651 
                 590 
                 651 
                 590 
                 651 
               
               
                 n (Patient) 
                  37 
                  40 
                  49 
                  28 
                  51 
                  26 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                   0.67 
                   0.68 
                   0.55 
                   0.67 
                   0.64 
                   0.58 
                   0.66 
                   0.62 
                   0.57 
               
               
                 SE 
                   0.059 
                   0.069 
                   0.066 
                   0.065 
                   0.075 
                   0.069 
                   0.070 
                   0.078 
                   0.070 
               
               
                 p Value 
                   0.0047 
                   0.0094 
                   0.43 
                   0.0080 
                   0.059 
                   0.24 
                   0.018 
                   0.13 
                   0.32 
               
               
                 nCohort Non-persistent 
                  41 
                  58 
                  37 
                  56 
                  61 
                  49 
                  61 
                  63 
                  51 
               
               
                 nCohort Persistent 
                  43 
                  23 
                  40 
                  28 
                  20 
                  28 
                  23 
                  18 
                  26 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Sensitivity 
                 79% 
                 87% 
                 78% 
                 82% 
                 85% 
                 82% 
                 83% 
                 83% 
                 81% 
               
               
                 Specificity 
                 29% 
                 29% 
                 27% 
                 29% 
                 28% 
                 29% 
                 28% 
                 27% 
                 27% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 63% 
                 70% 
                 52% 
                 71% 
                 65% 
                 57% 
                 74% 
                 61% 
                 58% 
               
               
                 Specificity 
                 63% 
                 57% 
                 51% 
                 61% 
                 54% 
                 53% 
                 59% 
                 52% 
                 53% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Sensitivity 
                 37% 
                 39% 
                 30% 
                 36% 
                 35% 
                 32% 
                 35% 
                 33% 
                 31% 
               
               
                 Specificity 
                 88% 
                 79% 
                 78% 
                 80% 
                 77% 
                 78% 
                 79% 
                 76% 
                 76% 
               
               
                 OR Quartile 2 
                  1.56 
                  2.76 
                  1.28 
                  1.84 
                  2.19 
                  1.84 
                  1.84 
                  1.85 
                  1.59 
               
               
                 p Value 
                  0.38 
                  0.14 
                  0.65 
                  0.29 
                  0.25 
                  0.30 
                  0.33 
                  0.38 
                  0.43 
               
               
                 Lower limit of 95% CI 
                  0.577 
                  0.725 
                  0.452 
                  0.596 
                  0.568 
                  0.583 
                  0.545 
                  0.475 
                  0.502 
               
               
                 Upper limit of 95% CI 
                  4.23 
                  10.5 
                  3.60 
                  5.68 
                  8.44 
                  5.80 
                  6.18 
                  7.19 
                  5.03 
               
               
                 OR Quartile 3 
                  2.92 
                  3.02 
                  1.17 
                  3.86 
                  2.19 
                  1.51 
                  4.08 
                  1.73 
                  1.53 
               
               
                 p Value 
                  0.018 
                  0.035 
                  0.74 
                  0.0069 
                  0.14 
                  0.39 
                  0.0094 
                  0.32 
                  0.38 
               
               
                 Lower limit of 95% CI 
                  1.21 
                  1.08 
                  0.477 
                  1.45 
                  0.768 
                  0.591 
                  1.41 
                  0.594 
                  0.592 
               
               
                 Upper limit of 95% CI 
                  7.10 
                  8.44 
                  2.85 
                  10.3 
                  6.24 
                  3.84 
                  11.8 
                  5.03 
                  3.98 
               
               
                 OR Quartile 4 
                  4.27 
                  2.46 
                  1.55 
                  2.27 
                  1.81 
                  1.64 
                  1.97 
                  1.60 
                  1.44 
               
               
                 p Value 
                  0.011 
                  0.093 
                  0.40 
                  0.11 
                  0.29 
                  0.35 
                  0.21 
                  0.42 
                  0.49 
               
               
                 Lower limit of 95% CI 
                  1.39 
                  0.861 
                  0.552 
                  0.823 
                  0.604 
                  0.579 
                  0.686 
                  0.512 
                  0.503 
               
               
                 Upper limit of 95% CI 
                  13.1 
                  7.05 
                  4.37 
                  6.28 
                  5.41 
                  4.62 
                  5.65 
                  5.00 
                  4.15 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort  
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 215 
                 280 
                 215 
                 293 
                 221 
                 302 
               
               
                 Average 
                 214 
                 298 
                 229 
                 320 
                 236 
                 322 
               
               
                 Stdev 
                  82.2 
                 136 
                  92.0 
                 146 
                 100 
                 147 
               
               
                 p (t-test) 
                   
                  0.0021 
                   
                  7.3E−4 
                   
                  0.0023 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 360 
                 651 
                 446 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                  32 
                  52 
                  50 
                  34 
                  55 
                  29 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 220 
                 304 
                 226 
                 302 
                 235 
                 307 
               
               
                 Average 
                 239 
                 316 
                 244 
                 317 
                 248 
                 316 
               
               
                 Stdev 
                 112 
                 132 
                 112 
                 138 
                 111 
                 146 
               
               
                 p (t-test) 
                   
                  0.0080 
                   
                  0.016 
                   
                  0.034 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                  54 
                  27 
                  58 
                  23 
                  61 
                  20 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 232 
                 255 
                 229 
                 260 
                 229 
                 260 
               
               
                 Average 
                 244 
                 286 
                 244 
                 304 
                 248 
                 302 
               
               
                 Stdev 
                  93.8 
                 140 
                  94.4 
                 152 
                 101 
                 150 
               
               
                 p (t-test) 
                   
                  0.15 
                   
                  0.034 
                   
                  0.064 
               
               
                 Min 
                 108 
                  73.7 
                  73.7 
                 105 
                  73.7 
                 105 
               
               
                 Max 
                 421 
                 651 
                 429 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                  30 
                  47 
                  44 
                  33 
                  46 
                  31 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.68 
                  0.68 
                  0.57 
                  0.68 
                  0.66 
                  0.60 
                  0.67 
                  0.64 
                  0.59 
               
               
                 SE 
                  0.058 
                  0.066 
                  0.066 
                  0.061 
                  0.070 
                  0.066 
                  0.064 
                  0.075 
                  0.067 
               
               
                 p Value 
                  0.0016 
                  0.0066 
                  0.29 
                  0.0024 
                  0.024 
                  0.13 
                  0.0074 
                  0.068 
                  0.18 
               
               
                 nCohort Non-persistent 
                  32 
                  54 
                  30 
                  50 
                  58 
                  44 
                  55 
                  61 
                  46 
               
               
                 nCohort Persistent 
                  52 
                  27 
                  47 
                  34 
                  23 
                  33 
                  29 
                  20 
                  31 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Sensitivity 
                 83% 
                 89% 
                 79% 
                 85% 
                 87% 
                 82% 
                 86% 
                 85% 
                 81% 
               
               
                 Specificity 
                 38% 
                 31% 
                 30% 
                 32% 
                 29% 
                 30% 
                 31% 
                 28% 
                 28% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 60% 
                 67% 
                 53% 
                 68% 
                 65% 
                 58% 
                 69% 
                 60% 
                 58% 
               
               
                 Specificity 
                 66% 
                 57% 
                 53% 
                 62% 
                 55% 
                 55% 
                 60% 
                 52% 
                 54% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Sensitivity 
                 35% 
                 37% 
                 30% 
                 35% 
                 35% 
                 33% 
                 34% 
                 35% 
                 32% 
               
               
                 Specificity 
                 91% 
                 80% 
                 80% 
                 82% 
                 78% 
                 80% 
                 80% 
                 77% 
                 78% 
               
               
                 OR Quartile 2 
                  2.87 
                  3.68 
                  1.59 
                  2.73 
                  2.76 
                  1.89 
                  2.80 
                  2.19 
                  1.64 
               
               
                 p Value 
                  0.042 
                  0.055 
                  0.39 
                  0.079 
                  0.14 
                  0.26 
                  0.093 
                  0.25 
                  0.38 
               
               
                 Lower limit of 95% CI 
                  1.04 
                  0.972 
                  0.556 
                  0.891 
                  0.725 
                  0.630 
                  0.842 
                  0.568 
                  0.547 
               
               
                 Upper limit of 95% CI 
                  7.90 
                  13.9 
                  4.52 
                  8.36 
                  10.5 
                  5.65 
                  9.29 
                  8.44 
                  4.92 
               
               
                 OR Quartile 3 
                  2.82 
                  2.70 
                  1.30 
                  3.41 
                  2.31 
                  1.63 
                  3.33 
                  1.66 
                  1.65 
               
               
                 p Value 
                  0.027 
                  0.044 
                  0.58 
                  0.0088 
                  0.10 
                  0.29 
                  0.013 
                  0.34 
                  0.29 
               
               
                 Lower limit of 95% CI 
                  1.13 
                  1.03 
                  0.519 
                  1.36 
                  0.847 
                  0.655 
                  1.28 
                  0.593 
                  0.657 
               
               
                 Upper limit of 95% CI 
                  7.04 
                  7.08 
                  3.25 
                  8.54 
                  6.29 
                  4.05 
                  8.65 
                  4.62 
                  4.13 
               
               
                 OR Quartile 4 
                  5.12 
                  2.30 
                  1.70 
                  2.48 
                  1.85 
                  1.94 
                  2.11 
                  1.81 
                  1.71 
               
               
                 p Value 
                  0.015 
                  0.11 
                  0.34 
                  0.077 
                  0.26 
                  0.21 
                  0.15 
                  0.29 
                  0.30 
               
               
                 Lower limit of 95% CI 
                  1.37 
                  0.826 
                  0.570 
                  0.907 
                  0.642 
                  0.694 
                  0.766 
                  0.604 
                  0.613 
               
               
                 Upper limit of 95% CI 
                  19.1 
                  6.40 
                  5.05 
                  6.81 
                  5.31 
                  5.45 
                  5.79 
                  5.41 
                  4.79 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 219 
                 279 
                 219 
                 285 
                 221 
                 285 
               
               
                 Average 
                 215 
                 296 
                 230 
                 316 
                 238 
                 314 
               
               
                 Stdev 
                  83.4 
                 135 
                  92.7 
                 146 
                 102 
                 145 
               
               
                 p (t-test) 
                   
                  0.0034 
                   
                  0.0014 
                   
                  0.0059 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 360 
                 651 
                 446 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                  31 
                  53 
                  49 
                  35 
                  53 
                  31 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 221 
                 303 
                 231 
                 292 
                 239 
                 302 
               
               
                 Average 
                 241 
                 311 
                 245 
                 311 
                 249 
                 309 
               
               
                 Stdev 
                 113 
                 132 
                 112 
                 138 
                 112 
                 146 
               
               
                 p (t-test) 
                   
                  0.014 
                   
                  0.027 
                   
                  0.056 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                  53 
                  28 
                  57 
                  24 
                  60 
                  21 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 232 
                 255 
                 235 
                 257 
                 235 
                 257 
               
               
                 Average 
                 244 
                 286 
                 244 
                 302 
                 249 
                 299 
               
               
                 Stdev 
                  93.8 
                 140 
                  95.5 
                 150 
                 102 
                 149 
               
               
                 p (t-test) 
                   
                  0.15 
                   
                  0.042 
                   
                  0.079 
               
               
                 Min 
                 108 
                  73.7 
                  73.7 
                 105 
                  73.7 
                 105 
               
               
                 Max 
                 421 
                 651 
                 429 
                 651 
                 512 
                 651 
               
               
                 n (Patient) 
                  30 
                  47 
                  43 
                  34 
                  45 
                  32 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.67 
                  0.66 
                  0.57 
                  0.67 
                  0.64 
                  0.60 
                  0.65 
                  0.62 
                  0.58 
               
               
                 SE 
                  0.059 
                  0.066 
                  0.066 
                  0.061 
                  0.070 
                  0.066 
                  0.064 
                  0.074 
                  0.067 
               
               
                 p Value 
                  0.0030 
                  0.012 
                  0.29 
                  0.0047 
                  0.042 
                  0.15 
                  0.016 
                  0.11 
                  0.21 
               
               
                 nCohort Non-persistent 
                  31 
                  53 
                  30 
                  49 
                  57 
                  43 
                  53 
                  60 
                  45 
               
               
                 nCohort Persistent 
                  53 
                  28 
                  47 
                  35 
                  24 
                  34 
                  31 
                  21 
                  32 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Sensitivity 
                 83% 
                 89% 
                 79% 
                 86% 
                 88% 
                 82% 
                 87% 
                 86% 
                 81% 
               
               
                 Specificity 
                 39% 
                 32% 
                 30% 
                 33% 
                 30% 
                 30% 
                 32% 
                 28% 
                 29% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 58% 
                 64% 
                 53% 
                 66% 
                 62% 
                 56% 
                 65% 
                 57% 
                 56% 
               
               
                 Specificity 
                 65% 
                 57% 
                 53% 
                 61% 
                 54% 
                 53% 
                 58% 
                 52% 
                 53% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Sensitivity 
                 34% 
                 36% 
                 30% 
                 34% 
                 33% 
                 32% 
                 32% 
                 33% 
                 31% 
               
               
                 Specificity 
                 90% 
                 79% 
                 80% 
                 82% 
                 77% 
                 79% 
                 79% 
                 77% 
                 78% 
               
               
                 OR Quartile 2 
                  3.09 
                  3.94 
                  1.59 
                  2.91 
                  2.98 
                  2.02 
                  3.19 
                  2.37 
                  1.76 
               
               
                 p Value 
                  0.030 
                  0.043 
                  0.39 
                  0.062 
                  0.11 
                  0.21 
                  0.058 
                  0.21 
                  0.31 
               
               
                 Lower limit of 95% CI 
                  1.12 
                  1.04 
                  0.556 
                  0.950 
                  0.782 
                  0.676 
                  0.962 
                  0.618 
                  0.588 
               
               
                 Upper limit of 95% CI 
                  8.55 
                  14.9 
                  4.52 
                  8.91 
                  11.3 
                  6.05 
                  10.6 
                  9.11 
                  5.27 
               
               
                 OR Quartile 3 
                  2.56 
                  2.35 
                  1.30 
                  3.03 
                  1.99 
                  1.46 
                  2.56 
                  1.43 
                  1.47 
               
               
                 p Value 
                  0.044 
                  0.077 
                  0.58 
                  0.016 
                  0.17 
                  0.41 
                  0.044 
                  0.49 
                  0.41 
               
               
                 Lower limit of 95% CI 
                  1.02 
                  0.913 
                  0.519 
                  1.23 
                  0.748 
                  0.590 
                  1.02 
                  0.523 
                  0.591 
               
               
                 Upper limit of 95% CI 
                  6.41 
                  6.04 
                  3.25 
                  7.47 
                  5.28 
                  3.60 
                  6.41 
                  3.88 
                  3.66 
               
               
                 OR Quartile 4 
                  4.80 
                  2.12 
                  1.70 
                  2.32 
                  1.69 
                  1.81 
                  1.82 
                  1.64 
                  1.59 
               
               
                 p Value 
                  0.020 
                  0.15 
                  0.34 
                  0.10 
                  0.33 
                  0.26 
                  0.24 
                  0.37 
                  0.38 
               
               
                 Lower limit of 95% CI 
                  1.28 
                  0.766 
                  0.570 
                  0.849 
                  0.592 
                  0.647 
                  0.666 
                  0.554 
                  0.570 
               
               
                 Upper limit of 95% CI 
                  18.0 
                  5.88 
                  5.05 
                  6.33 
                  4.84 
                  5.05 
                  4.96 
                  4.87 
                  4.44 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 216 
                 277 
                 211 
                 285 
                 216 
                 283 
               
               
                 Average 
                 215 
                 294 
                 227 
                 316 
                 232 
                 316 
               
               
                 Stdev 
                  84.8 
                 135 
                  91.7 
                 143 
                  97.1 
                 144 
               
               
                 p (t-test) 
                   
                  0.0043 
                   
                  9.1E−4 
                   
                  0.0019 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 360 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                  30 
                  54 
                  47 
                  37 
                  50 
                  34 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 221 
                 302 
                 231 
                 292 
                 235 
                 292 
               
               
                 Average 
                 240 
                 308 
                 245 
                 307 
                 248 
                 304 
               
               
                 Stdev 
                 115 
                 128 
                 114 
                 134 
                 115 
                 137 
               
               
                 p (t-test) 
                   
                  0.016 
                   
                  0.032 
                   
                  0.064 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                  51 
                  30 
                  55 
                  26 
                  57 
                  24 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 243 
                 252 
                 228 
                 260 
                 235 
                 257 
               
               
                 Average 
                 245 
                 285 
                 240 
                 302 
                 244 
                 299 
               
               
                 Stdev 
                  95.4 
                 139 
                  96.0 
                 145 
                  97.6 
                 146 
               
               
                 p (t-test) 
                   
                  0.18 
                   
                  0.030 
                   
                  0.051 
               
               
                 Min 
                 108 
                  73.7 
                  73.7 
                 105 
                  73.7 
                 105 
               
               
                 Max 
                 421 
                 651 
                 429 
                 651 
                 429 
                 651 
               
               
                 n (Patient) 
                  29 
                  48 
                  40 
                  37 
                  41 
                  36 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.67 
                  0.66 
                  0.57 
                  0.68 
                  0.64 
                  0.61 
                  0.67 
                  0.62 
                  0.59 
               
               
                 SE 
                  0.059 
                  0.064 
                  0.067 
                  0.060 
                  0.068 
                  0.064 
                  0.061 
                  0.070 
                  0.065 
               
               
                 p Value 
                  0.0036 
                  0.012 
                  0.33 
                  0.0024 
                  0.041 
                  0.086 
                  0.0053 
                  0.093 
                  0.15 
               
               
                 nCohort Non-persistent 
                  30 
                  51 
                  29 
                  47 
                  55 
                  40 
                  50 
                  57 
                  41 
               
               
                 nCohort Persistent 
                  54 
                  30 
                  48 
                  37 
                  26 
                  37 
                  34 
                  24 
                  36 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Sensitivity 
                 83% 
                 90% 
                 79% 
                 86% 
                 88% 
                 84% 
                 88% 
                 88% 
                 83% 
               
               
                 Specificity 
                 40% 
                 33% 
                 31% 
                 34% 
                 31% 
                 32% 
                 34% 
                 30% 
                 32% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 57% 
                 63% 
                 52% 
                 65% 
                 62% 
                 57% 
                 65% 
                 58% 
                 56% 
               
               
                 Specificity 
                 63% 
                 57% 
                 52% 
                 62% 
                 55% 
                 55% 
                 60% 
                 53% 
                 54% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Sensitivity 
                 33% 
                 33% 
                 29% 
                 35% 
                 31% 
                 32% 
                 32% 
                 29% 
                 31% 
               
               
                 Specificity 
                 90% 
                 78% 
                 79% 
                 83% 
                 76% 
                 80% 
                 80% 
                 75% 
                 78% 
               
               
                 OR Quartile 2 
                  3.33 
                  4.50 
                  1.71 
                  3.30 
                  3.43 
                  2.49 
                  3.86 
                  2.98 
                  2.32 
               
               
                 p Value 
                  0.021 
                  0.026 
                  0.32 
                  0.036 
                  0.070 
                  0.10 
                  0.027 
                  0.11 
                  0.13 
               
               
                 Lower limit of 95% CI 
                  1.20 
                  1.19 
                  0.598 
                  1.08 
                  0.905 
                  0.831 
                  1.17 
                  0.782 
                  0.776 
               
               
                 Upper limit of 95% CI 
                  9.27 
                  17.0 
                  4.89 
                  10.1 
                  13.0 
                  7.45 
                  12.8 
                  11.3 
                  6.95 
               
               
                 OR Quartile 3 
                  2.33 
                  2.28 
                  1.16 
                  2.97 
                  1.92 
                  1.60 
                  2.75 
                  1.56 
                  1.45 
               
               
                 p Value 
                  0.071 
                  0.082 
                  0.75 
                  0.017 
                  0.18 
                  0.30 
                  0.028 
                  0.37 
                  0.42 
               
               
                 Lower limit of 95% CI 
                  0.930 
                  0.901 
                  0.463 
                  1.22 
                  0.741 
                  0.652 
                  1.12 
                  0.593 
                  0.589 
               
               
                 Upper limit of 95% CI 
                  5.83 
                  5.75 
                  2.93 
                  7.28 
                  4.97 
                  3.95 
                  6.78 
                  4.08 
                  3.56 
               
               
                 OR Quartile 4 
                  4.50 
                  1.82 
                  1.58 
                  2.64 
                  1.44 
                  1.92 
                  1.91 
                  1.26 
                  1.56 
               
               
                 p Value 
                  0.026 
                  0.25 
                  0.41 
                  0.061 
                  0.50 
                  0.22 
                  0.20 
                  0.67 
                  0.39 
               
               
                 Lower limit of 95% CI 
                  1.20 
                  0.662 
                  0.529 
                  0.955 
                  0.508 
                  0.681 
                  0.705 
                  0.435 
                  0.562 
               
               
                 Upper limit of 95% CI 
                  16.8 
                  5.00 
                  4.71 
                  7.30 
                  4.06 
                  5.41 
                  5.19 
                  3.68 
                  4.36 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 216 
                 268 
                 211 
                 281 
                 216 
                 280 
               
               
                 Average 
                 216 
                 291 
                 228 
                 309 
                 233 
                 310 
               
               
                 Stdev 
                  86.9 
                 134 
                  93.3 
                 142 
                  98.6 
                 143 
               
               
                 p (t-test) 
                   
                  0.0091 
                   
                  0.0024 
                   
                  0.0048 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 360 
                 651 
                 446 
                 651 
                 446 
                 651 
               
               
                 n (Patient) 
                  28 
                  56 
                  45 
                  39 
                  48 
                  36 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 221 
                 302 
                 231 
                 292 
                 235 
                 292 
               
               
                 Average 
                 240 
                 308 
                 245 
                 307 
                 248 
                 304 
               
               
                 Stdev 
                 115 
                 128 
                 114 
                 134 
                 115 
                 137 
               
               
                 p (t-test) 
                   
                  0.016 
                   
                  0.032 
                   
                  0.064 
               
               
                 Min 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
                  73.7 
                  89.8 
               
               
                 Max 
                 651 
                 592 
                 651 
                 592 
                 651 
                 592 
               
               
                 n (Patient) 
                  51 
                  30 
                  55 
                  26 
                  57 
                  24 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 248 
                 249 
                 239 
                 255 
                 239 
                 255 
               
               
                 Average 
                 248 
                 282 
                 245 
                 294 
                 246 
                 295 
               
               
                 Stdev 
                  95.3 
                 139 
                  96.4 
                 145 
                  97.9 
                 146 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.082 
                   
                 0.081 
               
               
                 Min 
                 108 
                  73.7 
                  73.7 
                 105 
                  73.7 
                 105 
               
               
                 Max 
                 421 
                 651 
                 429 
                 651 
                 429 
                 651 
               
               
                 n (Patient) 
                  28 
                  49 
                  38 
                  39 
                  40 
                  37 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.66 
                  0.66 
                  0.55 
                  0.66 
                  0.64 
                  0.58 
                  0.65 
                  0.62 
                  0.58 
               
               
                 SE 
                  0.061 
                  0.064 
                  0.068 
                  0.060 
                  0.068 
                  0.065 
                  0.061 
                  0.070 
                  0.065 
               
               
                 p Value 
                  0.0096 
                  0.012 
                  0.49 
                  0.0061 
                  0.041 
                  0.23 
                  0.013 
                  0.093 
                  0.23 
               
               
                 nCohort Non-persistent 
                  28 
                  51 
                  28 
                  45 
                  55 
                  38 
                  48 
                  57 
                  40 
               
               
                 nCohort Persistent 
                  56 
                  30 
                  49 
                  39 
                  26 
                  39 
                  36 
                  24 
                  37 
               
               
                 Cutoff Quartile 2 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
                 169 
                 171 
                 174 
               
               
                 Sensitivity 
                 82% 
                 90% 
                 78% 
                 85% 
                 88% 
                 79% 
                 86% 
                 88% 
                 81% 
               
               
                 Specificity 
                 39% 
                 33% 
                 29% 
                 33% 
                 31% 
                 29% 
                 33% 
                 30% 
                 30% 
               
               
                 Cutoff Quartile 3 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
                 249 
               
               
                 Sensitivity 
                 55% 
                 63% 
                 51% 
                 62% 
                 62% 
                 54% 
                 61% 
                 58% 
                 54% 
               
               
                 Specificity 
                 61% 
                 57% 
                 50% 
                 60% 
                 55% 
                 53% 
                 58% 
                 53% 
                 52% 
               
               
                 Cutoff Quartile 4 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
                 332 
                 331 
                 335 
               
               
                 Sensitivity 
                 32% 
                 33% 
                 29% 
                 33% 
                 31% 
                 31% 
                 31% 
                 29% 
                 30% 
               
               
                 Specificity 
                 89% 
                 78% 
                 79% 
                 82% 
                 76% 
                 79% 
                 79% 
                 75% 
                 78% 
               
               
                 OR Quartile 2 
                  2.98 
                  4.50 
                  1.38 
                  2.75 
                  3.43 
                  1.58 
                  3.10 
                  2.98 
                  1.84 
               
               
                 p Value 
                  0.036 
                  0.026 
                  0.55 
                  0.063 
                  0.070 
                  0.39 
                  0.048 
                  0.11 
                  0.26 
               
               
                 Lower limit of 95% CI 
                  1.07 
                  1.19 
                  0.479 
                  0.945 
                  0.905 
                  0.554 
                  1.01 
                  0.782 
                  0.633 
               
               
                 Upper limit of 95% CI 
                  8.26 
                  17.0 
                  3.99 
                  8.00 
                  13.0 
                  4.50 
                  9.49 
                  11.3 
                  5.33 
               
               
                 OR Quartile 3 
                  1.92 
                  2.28 
                  1.04 
                  2.40 
                  1.92 
                  1.30 
                  2.20 
                  1.56 
                  1.30 
               
               
                 p Value 
                  0.17 
                  0.082 
                  0.93 
                  0.051 
                  0.18 
                  0.57 
                  0.080 
                  0.37 
                  0.57 
               
               
                 Lower limit of 95% CI 
                  0.761 
                  0.901 
                  0.412 
                  0.997 
                  0.741 
                  0.529 
                  0.911 
                  0.593 
                  0.531 
               
               
                 Upper limit of 95% CI 
                  4.83 
                  5.75 
                  2.64 
                  5.78 
                  4.97 
                  3.17 
                  5.32 
                  4.08 
                  3.19 
               
               
                 OR Quartile 4 
                  3.95 
                  1.82 
                  1.47 
                  2.31 
                  1.44 
                  1.67 
                  1.67 
                  1.26 
                  1.46 
               
               
                 p Value 
                  0.042 
                  0.25 
                  0.49 
                  0.10 
                  0.50 
                  0.33 
                  0.31 
                  0.67 
                  0.47 
               
               
                 Lower limit of 95% CI 
                  1.05 
                  0.662 
                  0.491 
                  0.839 
                  0.508 
                  0.592 
                  0.619 
                  0.435 
                  0.524 
               
               
                 Upper limit of 95% CI 
                  14.8 
                  5.00 
                  4.38 
                  6.37 
                  4.06 
                  4.69 
                  4.52 
                  3.68 
                  4.06 
               
               
                   
               
            
           
         
       
     
     Example 14. Use of C-C Motif Chemokine 16 for Evaluating Renal Status in Patients Admitted to the ICU: Persistent at RIFLE F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 16 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output. Two cohorts are defined to represent a “persistent” and a “non-persistent” population. “Persistent” indicates those patients whose minimum RIFLE stage during a period of 24, 48 or 72 hours is failure (F) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. “Non-persistent” indicates those patients who are not persistent at failure (F) and whose minimum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0), risk of injury (R), or injury (I) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. If a patient dies after failure (F) or is placed on renal replacement therapy (RRT) at any time from sample collection to 24, 48, 72, 96 or 168 hours after sample collection, the patient is considered “persistent”. 
     The ability to distinguish the “persistent” and “non-persistent” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 14.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0115 
                  0.0419 
                  0.0133 
                  0.0444 
                  0.0137 
                  0.0427 
               
               
                 Average 
                  0.0200 
                  0.195 
                  0.0235 
                  0.277 
                  0.0243 
                  0.293 
               
               
                 Stdev 
                  0.0260 
                  0.627 
                  0.0313 
                  0.783 
                  0.0318 
                  0.813 
               
               
                 p (t-test) 
                   
                  0.031 
                   
                  0.0074 
                   
                  0.0059 
               
               
                 Min 
                  4.13E−6 
                  6.68E−6 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                 2.98 
               
               
                 n (Patient) 
                 61 
                 22 
                 69 
                 14 
                 70 
                 13 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0124 
                  0.0487 
                  0.0142 
                  0.0329 
                  0.0151 
                  0.0305 
               
               
                 Average 
                  0.0226 
                  0.283 
                  0.0258 
                  0.335 
                  0.0318 
                  0.356 
               
               
                 Stdev 
                  0.0281 
                  0.782 
                  0.0326 
                  0.884 
                  0.0550 
                  0.983 
               
               
                 p (t-test) 
                   
                  0.0070 
                   
                  0.0037 
                   
                  0.0053 
               
               
                 Min 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 66 
                 14 
                 69 
                 11 
                 71 
                  9 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0108 
                  0.0473 
                  0.0133 
                  0.0671 
                  0.0133 
                  0.0671 
               
               
                 Average 
                  0.0214 
                  0.240 
                  0.0232 
                  0.420 
                  0.0232 
                  0.420 
               
               
                 Stdev 
                  0.0300 
                  0.711 
                  0.0307 
                  0.966 
                  0.0307 
                  0.966 
               
               
                 p (t-test) 
                   
                  0.017 
                   
                  6.4E−4 
                   
                  6.4E−4 
               
               
                 Min 
                  4.13E−6 
                  6.68E−6 
                  4.13E−6 
                  0.0305 
                  4.13E−6 
                  0.0305 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 61 
                 17 
                 69 
                  9 
                 69 
                  9 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.76 
                  0.78 
                  0.79 
                  0.77 
                  0.71 
                   0.89 
                  0.76 
                  0.64 
                   0.89 
               
               
                 SE 
                  0.065 
                  0.077 
                  0.070 
                  0.077 
                  0.092 
                   0.073 
                  0.082 
                  0.10 
                   0.073 
               
               
                 p Value 
                  9.3E−5 
                  3.6E−4 
                  3.0E−5 
                  3.8E−4 
                  0.021 
                   7.2E−8 
                  0.0017 
                  0.17 
                   7.2E−8 
               
               
                 nCohort Non-persistent 
                 61 
                 66 
                 61 
                 69 
                 69 
                  69 
                 70 
                 71 
                  69 
               
               
                 nCohort Persistent 
                 22 
                 14 
                 17 
                 14 
                 11 
                   9 
                 13 
                  9 
                   9 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                   0.00202 
                  0.00202 
                  0.00161 
                   0.00202 
               
               
                 Sensitivity 
                 86% 
                 93% 
                 88% 
                 93% 
                 91% 
                 100% 
                 92% 
                 89% 
                 100% 
               
               
                 Specificity 
                 28% 
                 29% 
                 28% 
                 28% 
                 28% 
                  28% 
                 27% 
                 27% 
                  28% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                   0.0155 
                  0.0157 
                  0.0165 
                   0.0155 
               
               
                 Sensitivity 
                 82% 
                 86% 
                 88% 
                 86% 
                 82% 
                 100% 
                 85% 
                 78% 
                 100% 
               
               
                 Specificity 
                 61% 
                 58% 
                 61% 
                 57% 
                 55% 
                  57% 
                 56% 
                 54% 
                  57% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                   0.0427 
                  0.0427 
                  0.0435 
                   0.0427 
               
               
                 Sensitivity 
                 50% 
                 57% 
                 59% 
                 57% 
                 45% 
                  78% 
                 54% 
                 33% 
                  78% 
               
               
                 Specificity 
                 82% 
                 82% 
                 82% 
                 80% 
                 78% 
                  80% 
                 79% 
                 76% 
                  80% 
               
               
                 OR Quartile 2 
                  2.45 
                  5.26 
                  2.90 
                  4.94 
                  3.80 
                   7.34 
                  4.47 
                  2.92 
                   7.34 
               
               
                 p Value 
                  0.19 
                  0.12 
                  0.19 
                  0.14 
                  0.22 
                   0.18 
                  0.16 
                  0.33 
                   0.18 
               
               
                 Lower limit of 95% CI 
                  0.641 
                  0.642 
                  0.598 
                  0.604 
                  0.455 
                   0.407 
                  0.544 
                  0.342 
                   0.407 
               
               
                 Upper limit of 95% CI 
                  9.35 
                  43.0 
                  14.0 
                  40.4 
                  31.7 
                   132 
                  36.8 
                  25.0 
                   132 
               
               
                 OR Quartile 3 
                  6.94 
                  8.14 
                  11.6 
                  7.80 
                  5.52 
                   24.6 
                  6.92 
                  4.03 
                   24.6 
               
               
                 p Value 
                  0.0015 
                  0.0090 
                  0.0021 
                  0.010 
                  0.037 
                   0.029 
                  0.016 
                  0.096 
                   0.029 
               
               
                 Lower limit of 95% CI 
                  2.09 
                  1.69 
                  2.42 
                  1.62 
                  1.11 
                   1.38 
                  1.43 
                  0.782 
                   1.38 
               
               
                 Upper limit of 95% CI 
                  23.0 
                  39.3 
                  55.2 
                  37.5 
                  27.4 
                 440 
                  33.6 
                  20.8 
                 440 
               
               
                 OR Quartile 4 
                  4.55 
                  6.00 
                  6.49 
                  5.24 
                  3.00 
                  13.8 
                  4.28 
                  1.59 
                  13.8 
               
               
                 p Value 
                  0.0051 
                  0.0043 
                  0.0017 
                  0.0073 
                  0.10 
                   0.0022 
                  0.021 
                  0.54 
                   0.0022 
               
               
                 Lower limit of 95% CI 
                  1.57 
                  1.75 
                  2.02 
                  1.56 
                  0.803 
                   2.57 
                  1.25 
                  0.358 
                   2.57 
               
               
                 Upper limit of 95% CI 
                 13.1 
                 20.5 
                 20.8 
                 17.6 
                 11.2 
                  73.6 
                 14.6 
                  7.04 
                  73.6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0112 
                  0.0411 
                  0.0128 
                  0.0427 
                  0.0133 
                  0.0389 
               
               
                 Average 
                  0.0197 
                  0.174 
                  0.0234 
                  0.233 
                  0.0242 
                  0.243 
               
               
                 Stdev 
                  0.0262 
                  0.589 
                  0.0317 
                  0.713 
                  0.0322 
                  0.735 
               
               
                 p (t-test) 
                   
                  0.048 
                   
                  0.018 
                   
                  0.016 
               
               
                 Min 
                  4.13E−6 
                  6.68E−6 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                 2.98 
               
               
                 n (Patient) 
                 58 
                 25 
                 66 
                 17 
                 67 
                 16 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0124 
                  0.0487 
                  0.0142 
                  0.0329 
                  0.0151 
                  0.0305 
               
               
                 Average 
                  0.0226 
                  0.283 
                  0.0258 
                  0.335 
                  0.0318 
                  0.356 
               
               
                 Stdev 
                  0.0281 
                  0.782 
                  0.0326 
                  0.884 
                  0.0550 
                  0.983 
               
               
                 p (t-test) 
                   
                  0.0070 
                   
                  0.0037 
                   
                  0.0053 
               
               
                 Min 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 66 
                 14 
                 69 
                 11 
                 71 
                  9 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.00924 
                  0.0427 
                  0.0124 
                  0.0539 
                  0.0124 
                  0.0539 
               
               
                 Average 
                  0.0209 
                  0.200 
                  0.0229 
                  0.300 
                  0.0229 
                  0.300 
               
               
                 Stdev 
                  0.0306 
                  0.642 
                  0.0313 
                  0.811 
                  0.0313 
                  0.811 
               
               
                 p (t-test) 
                   
                  0.037 
                   
                  0.0062 
                   
                  0.0062 
               
               
                 Min 
                  4.13E-6 
                  6.68E-6 
                  4.13E−6 
                  0.00279 
                  4.13E−6 
                  0.00279 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 57 
                 21 
                 65 
                 13 
                 65 
                 13 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.75 
                  0.78 
                  0.78 
                  0.75 
                  0.71 
                  0.82 
                  0.73 
                  0.64 
                  0.82 
               
               
                 SE 
                  0.063 
                  0.077 
                  0.065 
                  0.073 
                  0.092 
                  0.074 
                  0.076 
                  0.10 
                  0.074 
               
               
                 p Value 
                  7.4E−5 
                  3.6E−4 
                  1.8E−5 
                  5.5E−4 
                  0.021 
                  1.0E−5 
                  0.0022 
                  0.17 
                  1.0E−5 
               
               
                 nCohort Non-persistent 
                 58 
                 66 
                 57 
                 66 
                 69 
                  65 
                 67 
                 71 
                  65 
               
               
                 nCohort Persistent 
                 25 
                 14 
                 21 
                 17 
                 11 
                  13 
                 16 
                  9 
                  13 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                   0.00202 
               
               
                 Sensitivity 
                 88% 
                 93% 
                 90% 
                 94% 
                 91% 
                 100% 
                 94% 
                 89% 
                 100% 
               
               
                 Specificity 
                 29% 
                 29% 
                 30% 
                 29% 
                 28% 
                  29% 
                 28% 
                 27% 
                  29% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 80% 
                 86% 
                 86% 
                 82% 
                 82% 
                  92% 
                 81% 
                 78% 
                  92% 
               
               
                 Specificity 
                 62% 
                 58% 
                 63% 
                 58% 
                 55% 
                  58% 
                 57% 
                 54% 
                  58% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 48% 
                 57% 
                 52% 
                 53% 
                 45% 
                  62% 
                 50% 
                 33% 
                  62% 
               
               
                 Specificity 
                 83% 
                 82% 
                 82% 
                 80% 
                 78% 
                  80% 
                 79% 
                 76% 
                  80% 
               
               
                 OR Quartile 2 
                  3.04 
                  5.26 
                  4.04 
                  6.47 
                  3.80 
                  11.3 
                  5.94 
                  2.92 
                  11.3 
               
               
                 p Value 
                  0.10 
                  0.12 
                  0.080 
                  0.080 
                  0.22 
                  0.098 
                  0.095 
                  0.33 
                  0.098 
               
               
                 Lower limit of 95% CI 
                  0.802 
                  0.642 
                  0.845 
                  0.800 
                  0.455 
                  0.641 
                  0.732 
                  0.342 
                  0.641 
               
               
                 Upper limit of 95% CI 
                 11.5 
                 43.0 
                 19.3 
                 52.3 
                 31.7 
                 200 
                 48.1 
                 25.0 
                 200 
               
               
                 OR Quartile 3 
                  6.55 
                  8.14 
                 10.3 
                  6.33 
                  5.52 
                  16.9 
                  5.68 
                  4.03 
                  16.9 
               
               
                 p Value 
                  9.5E−4 
                 0.0090 
                 6.2E−4 
                 0.0069 
                 0.037 
                  0.0083 
                  0.011 
                  0.096 
                  0.0083 
               
               
                 Lower limit of 95% CI 
                  2.15 
                  1.69 
                  2.71 
                  1.66 
                  1.11 
                  2.07 
                  1.48 
                  0.782 
                  2.07 
               
               
                 Upper limit of 95% CI 
                 19.9 
                 39.3 
                 39.1 
                 24.2 
                 27.4 
                 138 
                 21.8 
                 20.8 
                 138 
               
               
                 OR Quartile 4 
                  4.43 
                  6.00 
                  5.17 
                  4.59 
                  3.00 
                  6.40 
                  3.79 
                  1.59 
                  6.40 
               
               
                 p Value 
                  0.0050 
                  0.0043 
                  0.0033 
                  0.0082 
                  0.10 
                  0.0042 
                 0.022 
                 0.54 
                  0.0042 
               
               
                 Lower limit of 95% CI 
                  1.57 
                  1.75 
                  1.73 
                  1.48 
                  0.803 
                  1.79 
                  1.21 
                  0.358 
                  1.79 
               
               
                 Upper limit of 95% CI 
                 12.5 
                 20.5 
                 15.5 
                 14.2 
                 11.2 
                  22.8 
                 11.9 
                  7.04 
                  22.8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0115 
                  0.0381 
                  0.0133 
                  0.0389 
                  0.0137 
                  0.0352 
               
               
                 Average 
                  0.0201 
                  0.168 
                  0.0237 
                  0.220 
                  0.0245 
                  0.228 
               
               
                 Stdev 
                  0.0263 
                  0.578 
                  0.0318 
                  0.694 
                  0.0323 
                  0.714 
               
               
                 p (t-test) 
                   
                  0.056 
                   
                  0.023 
                   
                  0.021 
               
               
                 Min 
                  6.68E−6 
                  4.13E−6 
                  4.13E−6 
                  1.26E−5 
                  4.13E−6 
                  1.26E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 57 
                 26 
                 65 
                 18 
                 66 
                 17 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0133 
                  0.0460 
                  0.0142 
                  0.0329 
                  0.0151 
                  0.0305 
               
               
                 Average 
                  0.0229 
                  0.265 
                  0.0258 
                  0.335 
                  0.0318 
                  0.356 
               
               
                 Stdev 
                  0.0282 
                  0.757 
                  0.0326 
                  0.884 
                  0.0550 
                  0.983 
               
               
                 p (t-test) 
                   
                  0.011 
                   
                  0.0037 
                   
                  0.0053 
               
               
                 Min 
                  6.68E−6 
                  4.13E−6 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 65 
                 15 
                 69 
                 11 
                 71 
                  9 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0100 
                  0.0419 
                  0.0133 
                  0.0427 
                  0.0128 
                  0.0483 
               
               
                 Average 
                  0.0213 
                  0.190 
                  0.0236 
                  0.260 
                  0.0232 
                  0.278 
               
               
                 Stdev 
                  0.0308 
                  0.628 
                  0.0315 
                  0.758 
                  0.0314 
                  0.783 
               
               
                 p (t-test) 
                   
                  0.046 
                   
                  0.014 
                   
                  0.0096 
               
               
                 Min 
                  6.68E−6 
                  4.13E−6 
                  6.68E−6 
                  4.13E−6 
                  4.13E−6 
                  1.26E−5 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 56 
                 22 
                 63 
                 15 
                 64 
                 14 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.72 
                  0.72 
                  0.74 
                  0.72 
                  0.71 
                  0.73 
                  0.70 
                  0.64 
                  0.78 
               
               
                 SE 
                  0.064 
                  0.080 
                  0.067 
                  0.074 
                  0.092 
                  0.080 
                  0.077 
                  0.10 
                  0.077 
               
               
                 p Value 
                  7.8E−4 
                  0.0056 
                  3.7E−4 
                  0.0027 
                  0.021 
                  0.0044 
                  0.0084 
                  0.17 
                  2.4E−4 
               
               
                 nCohort Non-persistent 
                 57 
                 65 
                 56 
                 65 
                 69 
                 63 
                 66 
                 71 
                 64 
               
               
                 nCohort Persistent 
                 26 
                 15 
                 22 
                 18 
                 11 
                 15 
                 17 
                  9 
                 14 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 85% 
                 87% 
                 86% 
                 89% 
                 91% 
                 87% 
                 88% 
                 89% 
                 93% 
               
               
                 Specificity 
                 28% 
                 28% 
                 29% 
                 28% 
                 28% 
                 27% 
                 27% 
                 27% 
                 28% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 77% 
                 80% 
                 82% 
                 78% 
                 82% 
                 80% 
                 76% 
                 78% 
                 86% 
               
               
                 Specificity 
                 61% 
                 57% 
                 62% 
                 57% 
                 55% 
                 57% 
                 56% 
                 54% 
                 58% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 46% 
                 53% 
                 50% 
                 50% 
                 45% 
                 53% 
                 47% 
                 33% 
                 57% 
               
               
                 Specificity 
                 82% 
                 82% 
                 82% 
                 80% 
                 78% 
                 79% 
                 79% 
                 76% 
                 80% 
               
               
                 OR Quartile 2 
                  2.15 
                  2.49 
                  2.53 
                  3.06 
                  3.80 
                  2.40 
                  2.81 
                  2.92 
                  5.09 
               
               
                 p Value 
                  0.22 
                  0.26 
                  0.18 
                  0.16 
                  0.22 
                  0.28 
                  0.20 
                  0.33 
                  0.13 
               
               
                 Lower limit of 95% CI 
                  0.639 
                  0.510 
                  0.658 
                  0.639 
                  0.455 
                  0.490 
                  0.584 
                  0.342 
                  0.619 
               
               
                 Upper limit of 95% CI 
                  7.21 
                  12.1 
                  9.76 
                  14.7 
                  31.7 
                  11.8 
                  13.5 
                  25.0 
                  41.8 
               
               
                 OR Quartile 3 
                  5.30 
                  5.29 
                  7.50 
                  4.62 
                  5.52 
                  5.33 
                  4.15 
                  4.03 
                  8.22 
               
               
                 p Value 
                  0.0020 
                  0.016 
                  0.0011 
                  0.013 
                  0.037 
                  0.016 
                  0.022 
                  0.096 
                  0.0088 
               
               
                 Lower limit of 95% CI 
                  1.84 
                  1.36 
                  2.23 
                  1.37 
                  1.11 
                  1.37 
                  1.22 
                  0.782 
                  1.70 
               
               
                 Upper limit of 95% CI 
                  15.3 
                  20.5 
                  25.2 
                  15.6 
                  27.4 
                  20.8 
                  14.1 
                  20.8 
                  39.8 
               
               
                 OR Quartile 4 
                  4.03 
                  5.05 
                  4.60 
                  4.00 
                  3.00 
                  4.40 
                  3.30 
                  1.59 
                  5.23 
               
               
                 p Value 
                  0.0080 
                  0.0078 
                  0.0056 
                  0.014 
                  0.10 
                  0.014 
                  0.037 
                  0.54 
                  0.0079 
               
               
                 Lower limit of 95% CI 
                  1.44 
                  1.53 
                  1.56 
                  1.32 
                  0.803 
                  1.35 
                  1.08 
                  0.358 
                  1.54 
               
               
                 Upper limit of 95% CI 
                 11.3 
                 16.6 
                 13.5 
                 12.1 
                 11.2 
                 14.4 
                 10.1 
                  7.04 
                 17.7 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0115 
                  0.0381 
                  0.0128 
                  0.0427 
                  0.0133 
                  0.0389 
               
               
                 Average 
                  0.0201 
                  0.168 
                  0.0233 
                  0.211 
                  0.0241 
                  0.219 
               
               
                 Stdev 
                  0.0263 
                  0.578 
                  0.0319 
                  0.675 
                  0.0324 
                  0.694 
               
               
                 p (t-test) 
                   
                  0.056 
                   
                  0.027 
                   
                  0.025 
               
               
                 Min 
                  6.68E−6 
                  4.13E−6 
                  4.13E−6 
                  1.26E−5 
                  4.13E−6 
                  1.26E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 57 
                 26 
                 64 
                 19 
                 65 
                 18 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0133 
                  0.0460 
                  0.0137 
                  0.0395 
                  0.0146 
                  0.0317 
               
               
                 Average 
                  0.0229 
                  0.265 
                  0.0254 
                  0.311 
                  0.0315 
                  0.325 
               
               
                 Stdev 
                  0.0282 
                  0.757 
                  0.0326 
                  0.847 
                  0.0553 
                  0.932 
               
               
                 p (t-test) 
                   
                  0.011 
                   
                  0.0055 
                   
                  0.0083 
               
               
                 Min 
                  6.68E−6 
                  4.13E−6 
                  4.13E−6 
                  1.60E−5 
                  4.13E−6 
                  1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 65 
                 15 
                 68 
                 12 
                 70 
                 10 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0100 
                  0.0419 
                  0.0128 
                  0.0471 
                  0.0124 
                  0.0514 
               
               
                 Average 
                  0.0213 
                  0.190 
                  0.0231 
                  0.247 
                  0.0228 
                  0.263 
               
               
                 Stdev 
                  0.0308 
                  0.628 
                  0.0316 
                  0.734 
                  0.0315 
                  0.757 
               
               
                 p (t-test) 
                   
                  0.046 
                   
                  0.017 
                   
                  0.012 
               
               
                 Min 
                  6.68E−6 
                  4.13E−6 
                  6.68E−6 
                  4.13E−6 
                  4.13E−6 
                  1.26E−5 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 56 
                 22 
                 62 
                 16 
                 63 
                 15 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.72 
                  0.72 
                  0.74 
                  0.73 
                  0.73 
                  0.74 
                  0.71 
                  0.67 
                  0.79 
               
               
                 SE 
                  0.064 
                  0.080 
                  0.067 
                  0.071 
                  0.088 
                  0.076 
                  0.074 
                  0.099 
                  0.073 
               
               
                 p Value 
                  7.8E−4 
                  0.0056 
                  3.7E−4 
                  0.0010 
                  0.0097 
                  0.0017 
                  0.0037 
                  0.094 
                  6.7E−5 
               
               
                 nCohort Non-persistent 
                 57 
                 65 
                 56 
                 64 
                 68 
                 62 
                 65 
                 70 
                 63 
               
               
                 nCohort Persistent 
                 26 
                 15 
                 22 
                 19 
                 12 
                 16 
                 18 
                 10 
                 15 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 85% 
                 87% 
                 86% 
                 89% 
                 92% 
                 88% 
                 89% 
                 90% 
                 93% 
               
               
                 Specificity 
                 28% 
                 28% 
                 29% 
                 28% 
                 28% 
                 27% 
                 28% 
                 27% 
                 29% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 77% 
                 80% 
                 82% 
                 79% 
                 83% 
                 81% 
                 78% 
                 80% 
                 87% 
               
               
                 Specificity 
                 61% 
                 57% 
                 62% 
                 58% 
                 56% 
                 58% 
                 57% 
                 54% 
                 59% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 46% 
                 53% 
                 50% 
                 53% 
                 50% 
                 56% 
                 50% 
                 40% 
                 60% 
               
               
                 Specificity 
                 82% 
                 82% 
                 82% 
                 81% 
                 79% 
                 81% 
                 80% 
                 77% 
                 81% 
               
               
                 OR Quartile 2 
                  2.15 
                  2.49 
                  2.53 
                  3.33 
                  4.27 
                  2.64 
                  3.06 
                  3.35 
                  5.60 
               
               
                 p Value 
                  0.22 
                  0.26 
                  0.18 
                  0.13 
                  0.18 
                  0.23 
                  0.16 
                  0.27 
                  0.11 
               
               
                 Lower limit of 95% CI 
                  0.639 
                  0.510 
                  0.658 
                  0.697 
                  0.515 
                  0.543 
                  0.639 
                  0.398 
                  0.685 
               
               
                 Upper limit of 95% CI 
                  7.21 
                  12.1 
                  9.76 
                  15.9 
                  35.3 
                  12.9 
                  14.7 
                  28.3 
                  45.8 
               
               
                 OR Quartile 3 
                  5.30 
                  5.29 
                  7.50 
                  5.14 
                  6.33 
                  6.00 
                  4.62 
                  4.75 
                  9.25 
               
               
                 p Value 
                  0.0020 
                  0.016 
                  0.0011 
                  0.0080 
                  0.023 
                  0.0094 
                  0.013 
                  0.059 
                  0.0055 
               
               
                 Lower limit of 95% CI 
                  1.84 
                  1.36 
                  2.23 
                  1.53 
                  1.29 
                  1.55 
                  1.37 
                  0.941 
                  1.92 
               
               
                 Upper limit of 95% CI 
                  15.3 
                  20.5 
                  25.2 
                  17.2 
                  31.1 
                  23.2 
                  15.6 
                  24.0 
                  44.5 
               
               
                 OR Quartile 4 
                  4.03 
                  5.05 
                  4.60 
                  4.81 
                  3.86 
                  5.36 
                  4.00 
                  2.25 
                  6.38 
               
               
                 p Value 
                  0.0080 
                  0.0078 
                  0.0056 
                  0.0050 
                  0.038 
                  0.0050 
                  0.014 
                  0.25 
                  0.0027 
               
               
                 Lower limit of 95% CI 
                  1.44 
                  1.53 
                  1.56 
                  1.61 
                  1.08 
                  1.66 
                  1.32 
                  0.565 
                  1.90 
               
               
                 Upper limit of 95% CI 
                 11.3 
                 16.6 
                 13.5 
                 14.4 
                 13.8 
                 17.3 
                 12.1 
                  8.97 
                 21.4 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0100 
                  0.0427 
                  0.0120 
                  0.0460 
                  0.0128 
                  0.0427 
               
               
                 Average 
                  0.0171 
                  0.158 
                  0.0212 
                  0.184 
                  0.0225 
                  0.196 
               
               
                 Stdev 
                  0.0234 
                  0.547 
                  0.0305 
                  0.614 
                  0.0311 
                  0.643 
               
               
                 p (t-test) 
                   
                  0.061 
                   
                  0.042 
                   
                  0.036 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 54 
                 29 
                 60 
                 23 
                 62 
                 21 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0124 
                  0.0487 
                  0.0133 
                  0.0460 
                  0.0137 
                  0.0395 
               
               
                 Average 
                  0.0219 
                  0.253 
                  0.0245 
                  0.294 
                  0.0253 
                  0.312 
               
               
                 Stdev 
                  0.0272 
                  0.733 
                  0.0320 
                  0.813 
                  0.0324 
                  0.846 
               
               
                 p (t-test) 
                   
                  0.012 
                   
                  0.0069 
                   
                  0.0054 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 1.60E−5 
                 4.13E−6 
                 1.60E−5 
               
               
                 Max 
                  0.113 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 64 
                 16 
                 67 
                 13 
                 68 
                 12 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.00924 
                  0.0444 
                  0.0116 
                  0.0467 
                  0.0108 
                  0.0473 
               
               
                 Average 
                  0.0196 
                  0.180 
                  0.0216 
                  0.206 
                  0.0213 
                  0.217 
               
               
                 Stdev 
                  0.0298 
                  0.601 
                  0.0311 
                  0.658 
                  0.0309 
                  0.674 
               
               
                 p (t-test) 
                   
                  0.052 
                   
                  0.034 
                   
                  0.027 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 6.68E−6 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 54 
                 24 
                 58 
                 20 
                 59 
                 19 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Resistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.76 
                  0.74 
                  0.77 
                  0.75 
                  0.75 
                  0.74 
                  0.72 
                  0.73 
                  0.78 
               
               
                 SE 
                  0.058 
                  0.076 
                  0.062 
                  0.065 
                  0.082 
                  0.069 
                  0.069 
                  0.087 
                  0.067 
               
               
                 p Value 
                 6.8E−6 
                  0.0013 
                 1.7E−5 
                 1.4E−4 
                  0.0023 
                 4.9E−4 
                  0.0015 
                  0.0081 
                 2.1E−5 
               
               
                 nCohort Non-persistent 
                 54 
                 64 
                 54 
                 60 
                 67 
                 58 
                 62 
                 68 
                 59 
               
               
                 nCohort Persistent 
                 29 
                 16 
                 24 
                 23 
                 13 
                 20 
                 21 
                 12 
                 19 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 86% 
                 88% 
                 88% 
                 87% 
                 92% 
                 85% 
                 86% 
                 92% 
                 89% 
               
               
                 Specificity 
                 30% 
                 28% 
                 30% 
                 28% 
                 28% 
                 28% 
                 27% 
                 28% 
                 29% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 79% 
                 81% 
                 83% 
                 78% 
                 85% 
                 80% 
                 76% 
                 83% 
                 84% 
               
               
                 Specificity 
                 65% 
                 58% 
                 65% 
                 60% 
                 57% 
                 60% 
                 58% 
                 56% 
                 61% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 52% 
                 56% 
                 54% 
                 57% 
                 54% 
                 60% 
                 52% 
                 50% 
                 63% 
               
               
                 Specificity 
                 87% 
                 83% 
                 85% 
                 85% 
                 81% 
                 84% 
                 82% 
                 79% 
                 85% 
               
               
                 OR Quartile 2 
                  2.63 
                  2.74 
                  2.95 
                  2.64 
                  4.75 
                  2.16 
                  2.27 
                  4.27 
                  3.44 
               
               
                 p Value 
                  0.12 
                  0.21 
                  0.11 
                  0.16 
                  0.15 
                  0.27 
                  0.23 
                  0.18 
                  0.12 
               
               
                 Lower limit of 95% CI 
                  0.788 
                  0.565 
                  0.769 
                  0.692 
                  0.577 
                  0.556 
                  0.591 
                  0.515 
                  0.716 
               
               
                 Upper limit of 95% CI 
                  8.79 
                 13.3 
                 11.3 
                 10.0 
                 39.1 
                  8.38 
                  8.69 
                 35.3 
                 16.5 
               
               
                 OR Quartile 3 
                  7.06 
                  5.94 
                  9.21 
                  5.40 
                  7.21 
                  6.09 
                  4.43 
                  6.33 
                  8.35 
               
               
                 p Value 
                 2.9E−4 
                 0.0097 
                 3.2E−4 
                 0.0031 
                 0.014 
                 0.0036 
                 0.0094 
                 0.023 
                 0.0019 
               
               
                 Lower limit of 95% CI 
                  2.45 
                  1.54 
                  2.75 
                  1.77 
                  1.48 
                  1.81 
                  1.44 
                  1.29 
                  2.19 
               
               
                 Upper limit of 95% CI 
                 20.3 
                 22.9 
                 30.9 
                 16.5 
                 35.1 
                 20.5 
                 13.6 
                 31.1 
                 31.9 
               
               
                 OR Quartile 4 
                 7.19 
                  6.19 
                  6.80 
                  7.37 
                  4.85 
                  8.17 
                  5.10 
                  3.86 
                  9.52 
               
               
                 p Value 
                 3.3E−4 
                 0.0025 
                 6.3E−4 
                 3.2E−4 
                  0.013 
                 3.2E−4 
                  0.0030 
                  0.038 
                 1.6E−4 
               
               
                 Lower limit of 95% CI 
                  2.45 
                  1.90 
                  2.26 
                  2.48 
                  1.39 
                  2.61 
                  1.74 
                  1.08 
                  2.95 
               
               
                 Upper limit of 95% CI 
                 21.1 
                 20.2 
                 20.4 
                 21.8 
                 16.9 
                 25.6 
                 15.0 
                 13.8 
                 30.7 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 7.94 
                 12.2 
                 8.73 
                 11.4 
                 8.89 
                 12.2 
               
               
                 Average 
                 10.6 
                 15.9 
                 11.3 
                 15.3 
                 11.3 
                 15.7 
               
               
                 Stdev 
                 6.93 
                 11.5 
                 7.58 
                 12.1 
                 7.52 
                 12.4 
               
               
                 p (t-test) 
                   
                 0.012 
                   
                 0.094 
                   
                 0.071 
               
               
                 Min 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 61 
                 23 
                 68 
                 16 
                 69 
                 15 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.00 
                 11.4 
                 9.75 
                 10.0 
                 9.66 
                 10.5 
               
               
                 Average 
                 11.9 
                 13.2 
                 12.1 
                 12.2 
                 12.1 
                 12.4 
               
               
                 Stdev 
                 8.56 
                 10.0 
                 8.54 
                 10.4 
                 8.49 
                 10.9 
               
               
                 p (t-test) 
                   
                 0.62 
                   
                 0.99 
                   
                 0.91 
               
               
                 Min 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 67 
                 14 
                 69 
                 12 
                 70 
                 11 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.23 
                 10.7 
                 9.56 
                 14.2 
                 9.56 
                 14.2 
               
               
                 Average 
                 11.1 
                 15.9 
                 11.6 
                 15.8 
                 11.6 
                 15.8 
               
               
                 Stdev 
                 7.07 
                 11.9 
                 7.66 
                 12.9 
                 7.66 
                 12.9 
               
               
                 p (t-test) 
                   
                 0.040 
                   
                 0.14 
                   
                 0.14 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 37.2 
                 38.9 
                 38.9 
                 36.8 
                 38.9 
                 36.8 
               
               
                 n (Patient) 
                 60 
                 17 
                 67 
                 10 
                 67 
                 10 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Durtion (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.65 
                 0.54 
                 0.60 
                 0.58 
                 0.49 
                 0.54 
                 0.59 
                 0.49 
                 0.54 
               
               
                 SE 
                 0.070 
                 0.087 
                 0.081 
                 0.082 
                 0.091 
                 0.10 
                 0.084 
                 0.095 
                 0.10 
               
               
                 p Value 
                 0.039 
                 0.63 
                 0.22 
                 0.31 
                 0.88 
                 0.65 
                 0.29 
                 0.89 
                 0.65 
               
               
                 nCohort Non-persistent 
                 61 
                 67 
                 60 
                 68 
                 69 
                 67 
                 69 
                 70 
                 67 
               
               
                 nCohort Persistent 
                 23 
                 14 
                 17 
                 16 
                 12 
                 10 
                 15 
                 11 
                 10 
               
               
                 Cutoff Quartile 2 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
               
               
                 Sensitivity 
                 83% 
                 79% 
                 76% 
                 75% 
                 75% 
                 60% 
                 73% 
                 73% 
                 60% 
               
               
                 Specificity 
                 28% 
                 25% 
                 25% 
                 25% 
                 25% 
                 22% 
                 25% 
                 24% 
                 22% 
               
               
                 Cutoff Quartile 3 
                 9.66 
                 9.75 
                 9.75 
                 9.66 
                 9.75 
                 9.75 
                 9.66 
                 9.75 
                 9.75 
               
               
                 Sensitivity 
                 65% 
                 57% 
                 59% 
                 62% 
                 50% 
                 60% 
                 67% 
                 55% 
                 60% 
               
               
                 Specificity 
                 56% 
                 51% 
                 52% 
                 53% 
                 49% 
                 51% 
                 54% 
                 50% 
                 51% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
               
               
                 Sensitivity 
                 39% 
                 36% 
                 41% 
                 38% 
                 25% 
                 50% 
                 40% 
                 27% 
                 50% 
               
               
                 Specificity 
                 80% 
                 76% 
                 78% 
                 78% 
                 74% 
                 78% 
                 78% 
                 74% 
                 78% 
               
               
                 OR Quartile 2 
                 1.84 
                 1.25 
                 1.08 
                 1.00 
                 0.981 
                 0.433 
                 0.899 
                 0.855 
                 0.433 
               
               
                 p Value 
                 0.33 
                 0.76 
                 0.90 
                 1.0 
                 0.98 
                 0.24 
                 0.87 
                 0.83 
                 0.24 
               
               
                 Lower limit of 95% CI 
                 0.545 
                 0.310 
                 0.306 
                 0.284 
                 0.238 
                 0.108 
                 0.253 
                 0.204 
                 0.108 
               
               
                 Upper limit of 95% CI 
                 6.18 
                 5.01 
                 3.83 
                 3.52 
                 4.04 
                 1.74 
                 3.20 
                 3.59 
                 1.74 
               
               
                 OR Quartile 3 
                 2.36 
                 1.37 
                 1.53 
                 1.88 
                 0.971 
                 1.55 
                 2.31 
                 1.20 
                 1.55 
               
               
                 p Value 
                 0.091 
                 0.59 
                 0.45 
                 0.27 
                 0.96 
                 0.53 
                 0.16 
                 0.78 
                 0.53 
               
               
                 Lower limit of 95% CI 
                 0.872 
                 0.430 
                 0.513 
                 0.613 
                 0.285 
                 0.400 
                 0.715 
                 0.335 
                 0.400 
               
               
                 Upper limit of 95% CI 
                 6.39 
                 4.39 
                 4.54 
                 5.74 
                 3.31 
                 5.98 
                 7.47 
                 4.30 
                 5.98 
               
               
                 OR Quartile 4 
                 2.62 
                 1.77 
                 2.53 
                 2.12 
                 0.944 
                 3.47 
                 2.40 
                 1.08 
                 3.47 
               
               
                 p Value 
                 0.071 
                 0.36 
                 0.11 
                 0.21 
                 0.94 
                 0.075 
                 0.15 
                 0.91 
                 0.075 
               
               
                 Lower limit of 95% CI 
                 0.920 
                 0.518 
                 0.806 
                 0.662 
                 0.230 
                 0.884 
                 0.737 
                 0.259 
                 0.884 
               
               
                 Upper limit of 95% CI 
                 7.49 
                 6.05 
                 7.95 
                 6.78 
                 3.88 
                 13.6 
                 7.82 
                 4.53 
                 13.6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.17 
                 11.5 
                 8.89 
                 10.5 
                 8.94 
                 11.4 
               
               
                 Average 
                 10.7 
                 15.5 
                 11.4 
                 14.8 
                 11.3 
                 15.1 
               
               
                 Stdev 
                 6.97 
                 11.4 
                 7.61 
                 11.9 
                 7.56 
                 12.2 
               
               
                 p (t-test) 
                   
                 0.021 
                   
                 0.14 
                   
                 0.12 
               
               
                 Min 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 60 
                 24 
                 67 
                 17 
                 68 
                 16 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.00 
                 11.4 
                 9.75 
                 10.0 
                 9.66 
                 10.5 
               
               
                 Average 
                 11.9 
                 13.2 
                 12.1 
                 12.2 
                 12.1 
                 12.4 
               
               
                 Stdev 
                 8.56 
                 10.0 
                 8.54 
                 10.4 
                 8.49 
                 10.9 
               
               
                 p (t-test) 
                   
                 0.62 
                   
                 0.99 
                   
                 0.91 
               
               
                 Min 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 67 
                 14 
                 69 
                 12 
                 70 
                 11 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.23 
                 10.7 
                 9.56 
                 14.2 
                 9.56 
                 14.2 
               
               
                 Average 
                 10.7 
                 16.5 
                 11.3 
                 16.8 
                 11.3 
                 16.8 
               
               
                 Stdev 
                 6.27 
                 12.5 
                 7.05 
                 13.6 
                 7.05 
                 13.6 
               
               
                 p (t-test) 
                   
                 0.0094 
                   
                 0.038 
                   
                 0.038 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 58 
                 19 
                 65 
                 12 
                 65 
                 12 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.63 
                 0.54 
                 0.61 
                 0.56 
                 0.49 
                 0.56 
                 0.57 
                 0.49 
                 0.56 
               
               
                 SE 
                 0.070 
                 0.087 
                 0.077 
                 0.080 
                 0.091 
                 0.093 
                 0.082 
                 0.095 
                 0.093 
               
               
                 p Value 
                 0.063 
                 0.63 
                 0.15 
                 0.42 
                 0.88 
                 0.49 
                 0.41 
                 0.89 
                 0.49 
               
               
                 nCohort Non-persistent 
                 60 
                 67 
                 58 
                 67 
                 69 
                 65 
                 68 
                 70 
                 65 
               
               
                 nCohort Persistent 
                 24 
                 14 
                 19 
                 17 
                 12 
                 12 
                 16 
                 11 
                 12 
               
               
                 Cutoff Quartile 2 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
               
               
                 Sensitivity 
                 83% 
                 79% 
                 79% 
                 76% 
                 75% 
                 67% 
                 75% 
                 73% 
                 67% 
               
               
                 Specificity 
                 28% 
                 25% 
                 26% 
                 25% 
                 25% 
                 23% 
                 25% 
                 24% 
                 23% 
               
               
                 Cutoff Quartile 3 
                 9.66 
                 9.75 
                 9.75 
                 9.66 
                 9.75 
                 9.75 
                 9.66 
                 9.75 
                 9.75 
               
               
                 Sensitivity 
                 62% 
                 57% 
                 58% 
                 59% 
                 50% 
                 58% 
                 62% 
                 55% 
                 58% 
               
               
                 Specificity 
                 55% 
                 51% 
                 52% 
                 52% 
                 49% 
                 51% 
                 53% 
                 50% 
                 51% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
               
               
                 Sensitivity 
                 38% 
                 36% 
                 42% 
                 35% 
                 25% 
                 50% 
                 38% 
                 27% 
                 50% 
               
               
                 Specificity 
                 80% 
                 76% 
                 79% 
                 78% 
                 74% 
                 78% 
                 78% 
                 74% 
                 78% 
               
               
                 OR Quartile 2 
                 1.98 
                 1.25 
                 1.31 
                 1.10 
                 0.981 
                 0.600 
                 1.00 
                 0.855 
                 0.600 
               
               
                 p Value 
                 0.27 
                 0.76 
                 0.67 
                 0.88 
                 0.98 
                 0.45 
                 1.0 
                 0.83 
                 0.45 
               
               
                 Lower limit of 95% CI 
                 0.589 
                 0.310 
                 0.375 
                 0.317 
                 0.238 
                 0.158 
                 0.284 
                 0.204 
                 0.158 
               
               
                 Upper limit of 95% CI 
                 6.64 
                 5.01 
                 4.56 
                 3.85 
                 4.04 
                 2.27 
                 3.52 
                 3.59 
                 2.27 
               
               
                 OR Quartile 3 
                 2.04 
                 1.37 
                 1.47 
                 1.56 
                 0.971 
                 1.44 
                 1.88 
                 1.20 
                 1.44 
               
               
                 p Value 
                 0.15 
                 0.59 
                 0.47 
                 0.42 
                 0.96 
                 0.56 
                 0.27 
                 0.78 
                 0.56 
               
               
                 Lower limit of 95% CI 
                 0.772 
                 0.430 
                 0.517 
                 0.532 
                 0.285 
                 0.415 
                 0.613 
                 0.335 
                 0.415 
               
               
                 Upper limit of 95% CI 
                 5.38 
                 4.39 
                 4.19 
                 4.59 
                 3.31 
                 5.02 
                 5.74 
                 4.30 
                 5.02 
               
               
                 OR Quartile 4 
                 2.40 
                 1.77 
                 2.79 
                 1.89 
                 0.944 
                 3.64 
                 2.12 
                 1.08 
                 3.64 
               
               
                 p Value 
                 0.099 
                 0.36 
                 0.070 
                 0.28 
                 0.94 
                 0.047 
                 0.21 
                 0.91 
                 0.047 
               
               
                 Lower limit of 95% CI 
                 0.848 
                 0.518 
                 0.918 
                 0.600 
                 0.230 
                 1.02 
                 0.662 
                 0.259 
                 1.02 
               
               
                 Upper limit of 95% CI 
                 6.80 
                 6.05 
                 8.46 
                 5.96 
                 3.88 
                 13.1 
                 6.78 
                 4.53 
                 13.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 8.41 
                 10.7 
                 8.73 
                 10.6 
                 8.89 
                 10.7 
               
               
                 Average 
                 10.8 
                 15.0 
                 11.4 
                 14.6 
                 11.4 
                 14.9 
               
               
                 Stdev 
                 6.95 
                 11.4 
                 7.67 
                 11.6 
                 7.61 
                 11.9 
               
               
                 p (t-test) 
                   
                 0.043 
                   
                 0.17 
                   
                 0.13 
               
               
                 Min 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 59 
                 25 
                 66 
                 18 
                 67 
                 17 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.37 
                 10.5 
                 9.75 
                 10.0 
                 9.66 
                 10.5 
               
               
                 Average 
                 12.0 
                 12.5 
                 12.1 
                 12.2 
                 12.1 
                 12.4 
               
               
                 Stdev 
                 8.55 
                 10.0 
                 8.54 
                 10.4 
                 8.49 
                 10.9 
               
               
                 p (t-test) 
                   
                 0.86 
                   
                 0.99 
                   
                 0.91 
               
               
                 Min 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
                 1.53 
                 1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 66 
                 15 
                 69 
                 12 
                 70 
                 11 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 9.56 
                 10.3 
                 9.56 
                 10.3 
                 9.28 
                 10.7 
               
               
                 Average 
                 10.9 
                 15.8 
                 11.4 
                 15.4 
                 11.3 
                 16.4 
               
               
                 Stdev 
                 6.23 
                 12.6 
                 7.08 
                 13.2 
                 7.11 
                 13.2 
               
               
                 p (t-test) 
                   
                 0.024 
                   
                 0.12 
                   
                 0.050 
               
               
                 Min 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
                 1.62 
                 1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 57 
                 20 
                 63 
                 14 
                 64 
                 13 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.60 
                 0.50 
                 0.58 
                 0.57 
                 0.49 
                 0.52 
                 0.57 
                 0.49 
                 0.57 
               
               
                 SE 
                 0.069 
                 0.083 
                 0.076 
                 0.078 
                 0.091 
                 0.087 
                 0.080 
                 0.095 
                 0.090 
               
               
                 p Value 
                 0.14 
                 0.96 
                 0.32 
                 0.38 
                 0.88 
                 0.77 
                 0.37 
                 0.89 
                 0.45 
               
               
                 nCohort Non-persistent 
                 59 
                 66 
                 57 
                 66 
                 69 
                 63 
                 67 
                 70 
                 64 
               
               
                 nCohort Persistent 
                 25 
                 15 
                 20 
                 18 
                 12 
                 14 
                 17 
                 11 
                 13 
               
               
                 Cutoff Quartile 2 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
                 6.19 
                 6.19 
                 6.24 
               
               
                 Sensitivity 
                 80% 
                 73% 
                 75% 
                 78% 
                 75% 
                 64% 
                 76% 
                 73% 
                 69% 
               
               
                 Specificity 
                 27% 
                 24% 
                 25% 
                 26% 
                 25% 
                 22% 
                 25% 
                 24% 
                 23% 
               
               
                 Cutoff Quartile 3 
                 9.66 
                 9.75 
                 9.75 
                 9.66 
                 9.75 
                 9.75 
                 9.66 
                 9.75 
                 9.75 
               
               
                 Sensitivity 
                 60% 
                 53% 
                 55% 
                 61% 
                 50% 
                 57% 
                 65% 
                 55% 
                 62% 
               
               
                 Specificity 
                 54% 
                 50% 
                 51% 
                 53% 
                 49% 
                 51% 
                 54% 
                 50% 
                 52% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
               
               
                 Sensitivity 
                 36% 
                 33% 
                 40% 
                 33% 
                 25% 
                 43% 
                 35% 
                 27% 
                 46% 
               
               
                 Specificity 
                 80% 
                 76% 
                 79% 
                 77% 
                 74% 
                 78% 
                 78% 
                 74% 
                 78% 
               
               
                 OR Quartile 2 
                 1.49 
                 0.880 
                 0.977 
                 1.21 
                 0.981 
                 0.514 
                 1.10 
                 0.855 
                 0.689 
               
               
                 p Value 
                 0.49 
                 0.84 
                 0.97 
                 0.76 
                 0.98 
                 0.29 
                 0.88 
                 0.83 
                 0.58 
               
               
                 Lower limit of 95% CI 
                 0.478 
                 0.246 
                 0.301 
                 0.351 
                 0.238 
                 0.148 
                 0.317 
                 0.204 
                 0.185 
               
               
                 Upper limit of 95% CI 
                 4.63 
                 3.15 
                 3.17 
                 4.20 
                 4.04 
                 1.78 
                 3.85 
                 3.59 
                 2.56 
               
               
                 OR Quartile 3 
                 1.78 
                 1.14 
                 1.27 
                 1.77 
                 0.971 
                 1.38 
                 2.13 
                 1.20 
                 1.70 
               
               
                 p Value 
                 0.24 
                 0.82 
                 0.65 
                 0.29 
                 0.96 
                 0.59 
                 0.18 
                 0.78 
                 0.39 
               
               
                 Lower limit of 95% CI 
                 0.688 
                 0.372 
                 0.455 
                 0.612 
                 0.285 
                 0.428 
                 0.705 
                 0.335 
                 0.503 
               
               
                 Upper limit of 95% CI 
                 4.60 
                 3.51 
                 3.52 
                 5.14 
                 3.31 
                 4.43 
                 6.43 
                 4.30 
                 5.77 
               
               
                 OR Quartile 4 
                 2.20 
                 1.56 
                 2.50 
                 1.70 
                 0.944 
                 2.62 
                 1.89 
                 1.08 
                 3.06 
               
               
                 p Value 
                 0.13 
                 0.47 
                 0.10 
                 0.36 
                 0.94 
                 0.12 
                 0.28 
                 0.91 
                 0.077 
               
               
                 Lower limit of 95% CI 
                 0.784 
                 0.465 
                 0.834 
                 0.546 
                 0.230 
                 0.780 
                 0.600 
                 0.259 
                 0.885 
               
               
                 Upper limit of 95% CI 
                 6.19 
                 5.25 
                 7.50 
                 5.30 
                 3.88 
                 8.84 
                 5.96 
                 4.53 
                 10.6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  8.41 
                 10.7 
                  8.56 
                 10.7 
                  8.73 
                 11.5 
               
               
                 Average 
                 10.8 
                 15.0 
                 11.2 
                 15.0 
                 11.2 
                 15.3 
               
               
                 Stdev 
                  6.95 
                 11.4 
                  7.60 
                 11.4 
                 7.55 
                 11.7 
               
               
                 p (t-test) 
                   
                 0.043 
                   
                 0.094 
                   
                  0.074 
               
               
                 Min 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 59 
                 25 
                 65 
                 19 
                 66 
                 18 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  9.37 
                 10.5 
                  9.37 
                 10.5 
                  9.56 
                 11.4 
               
               
                 Average 
                 12.0 
                 12.5 
                 12.0 
                 13.0 
                 11.9 
                 13.2 
               
               
                 Stdev 
                  8.55 
                 10.0 
                  8.51 
                 10.4 
                  8.45 
                 10.8 
               
               
                 p (t-test) 
                   
                  0.86 
                   
                  0.71 
                   
                  0.64 
               
               
                 Min 
                 1.53 
                  1.32 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 66 
                 15 
                 68 
                 13 
                 69 
                 12 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  9.56 
                 10.3 
                  9.28 
                 10.7 
                  9.00 
                 14.6 
               
               
                 Average 
                 10.9 
                 15.8 
                 11.3 
                 15.9 
                 11.1 
                 16.8 
               
               
                 Stdev 
                  6.23 
                 12.6 
                  7.00 
                 12.8 
                 7.02 
                 12.7 
               
               
                 p (t-test) 
                   
                  0.024 
                   
                  0.060 
                   
                  0.023 
               
               
                 Min 
                  1.62 
                  1.32 
                 1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 57 
                 20 
                 62 
                 15 
                 63 
                 14 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.60 
                  0.50 
                  0.58 
                  0.59 
                  0.52 
                  0.55 
                  0.60 
                  0.52 
                  0.60 
               
               
                 SE 
                  0.069 
                  0.083 
                  0.076 
                  0.077 
                  0.089 
                  0.085 
                  0.078 
                  0.092 
                  0.087 
               
               
                 p Value 
                  0.14 
                  0.96 
                  0.32 
                  0.23 
                  0.82 
                  0.53 
                  0.22 
                  0.80 
                  0.27 
               
               
                 nCohort Non-persistent 
                 59 
                 66 
                 57 
                 65 
                 68 
                 62 
                 66 
                 69 
                 63 
               
               
                 nCohort Persistent 
                 25 
                 15 
                 20 
                 19 
                 13 
                 15 
                 18 
                 12 
                 14 
               
               
                 Cutoff Quartile 2 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
               
               
                 Sensitivity 
                 80% 
                 73% 
                 75% 
                 79% 
                 77% 
                 67% 
                 78% 
                 75% 
                 71% 
               
               
                 Specificity 
                 27% 
                 24% 
                 25% 
                 26% 
                 25% 
                 23% 
                 26% 
                 25% 
                 24% 
               
               
                 Cutoff Quartile 3 
                  9.66 
                  9.75 
                  9.75 
                  9.66 
                  9.75 
                  9.75 
                  9.66 
                  9.75 
                  9.75 
               
               
                 Sensitivity 
                 60% 
                 53% 
                 55% 
                 63% 
                 54% 
                 60% 
                 67% 
                 58% 
                 64% 
               
               
                 Specificity 
                 54% 
                 50% 
                 51% 
                 54% 
                 50% 
                 52% 
                 55% 
                 51% 
                 52% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
               
               
                 Sensitivity 
                 36% 
                 33% 
                 40% 
                 37% 
                 31% 
                 47% 
                 39% 
                 33% 
                 50% 
               
               
                 Specificity 
                 80% 
                 76% 
                 79% 
                 78% 
                 75% 
                 79% 
                 79% 
                 75% 
                 79% 
               
               
                 OR Quartile 2 
                  1.49 
                  0.880 
                  0.977 
                  1.33 
                  1.11 
                  0.583 
                  1.21 
                  0.981 
                  0.781 
               
               
                 p Value 
                  0.49 
                  0.84 
                  0.97 
                  0.65 
                  0.88 
                  0.39 
                  0.76 
                  0.98 
                  0.71 
               
               
                 Lower limit of 95% CI 
                  0.478 
                  0.246 
                  0.301 
                  0.387 
                  0.273 
                  0.171 
                  0.351 
                  0.238 
                  0.214 
               
               
                 Upper limit of 95% CI 
                  4.63 
                  3.15 
                  3.17 
                  4.56 
                  4.52 
                  1.99 
                  4.20 
                  4.04 
                  2.86 
               
               
                 OR Quartile 3 
                  1.78 
                  1.14 
                  1.27 
                  2.00 
                  1.17 
                  1.60 
                  2.40 
                  1.44 
                  1.98 
               
               
                 p Value 
                  0.24 
                  0.82 
                  0.65 
                  0.20 
                  0.80 
                  0.42 
                  0.12 
                  0.56 
                  0.26 
               
               
                 Lower limit of 95% CI 
                  0.688 
                  0.372 
                  0.455 
                  0.698 
                  0.355 
                  0.508 
                  0.804 
                  0.417 
                  0.596 
               
               
                 Upper limit of 95% CI 
                  4.60 
                  3.51 
                  3.52 
                  5.73 
                  3.83 
                  5.04 
                  7.16 
                  4.98 
                  6.57 
               
               
                 OR Quartile 4 
                  2.20 
                  1.56 
                  2.50 
                  2.12 
                  1.33 
                  3.30 
                  2.36 
                  1.53 
                  3.85 
               
               
                 p Value 
                  0.13 
                  0.47 
                  0.10 
                  0.18 
                  0.66 
                  0.048 
                  0.13 
                  0.53 
                  0.029 
               
               
                 Lower limit of 95% CI 
                  0.784 
                  0.465 
                  0.834 
                  0.705 
                  0.364 
                  1.01 
                  0.774 
                  0.409 
                  1.14 
               
               
                 Upper limit of 95% CI 
                  6.19 
                  5.25 
                  7.50 
                  6.41 
                  4.89 
                  10.8 
                  7.22 
                  5.72 
                  12.9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  8.56 
                 10.5 
                  8.73 
                 10.2 
                  8.73 
                 10.6 
               
               
                 Average 
                 11.0 
                 14.4 
                 11.4 
                 13.9 
                 11.3 
                 14.5 
               
               
                 Stdev 
                  7.01 
                 11.2 
                  7.72 
                 10.9 
                  7.62 
                 11.3 
               
               
                 p (t-test) 
                   
                  0.096 
                   
                  0.24 
                   
                  0.16 
               
               
                 Min 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 57 
                 27 
                 62 
                 22 
                 64 
                 20 
               
            
           
           
               
            
               
                  sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  9.37 
                 10.5 
                  9.37 
                 10.5 
                  9.56 
                 11.4 
               
               
                 Average 
                 12.0 
                 12.5 
                 12.0 
                 13.0 
                 11.9 
                 13.2 
               
               
                 Stdev 
                  8.55 
                 10.0 
                  8.51 
                 10.4 
                  8.45 
                 10.8 
               
               
                 p (t-test) 
                   
                  0.86 
                   
                  0.71 
                   
                  0.64 
               
               
                 Min 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
                  1.53 
                  1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 66 
                 15 
                 68 
                 13 
                 69 
                 12 
               
            
           
           
               
            
               
                  UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  9.23 
                 10.7 
                  9.56 
                 10.3 
                  9.23 
                 10.7 
               
               
                 Average 
                 10.8 
                 15.7 
                 11.3 
                 14.8 
                 11.2 
                 15.5 
               
               
                 Stdev 
                  6.29 
                 12.3 
                  7.15 
                 11.9 
                  7.18 
                 11.9 
               
               
                 p (t-test) 
                   
                  0.027 
                   
                  0.13 
                   
                  0.064 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 56 
                 21 
                 59 
                 18 
                 60 
                 17 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.57 
                  0.50 
                  0.58 
                  0.55 
                  0.52 
                  0.55 
                  0.56 
                  0.52 
                  0.58 
               
               
                 SE 
                  0.068 
                  0.083 
                  0.075 
                  0.073 
                  0.089 
                  0.079 
                  0.075 
                  0.092 
                  0.081 
               
               
                 p Value 
                  0.29 
                  0.96 
                  0.27 
                  0.47 
                  0.82 
                  0.56 
                  0.40 
                  0.80 
                  0.31 
               
               
                 nCohort Non-persistent 
                 57 
                 66 
                 56 
                 62 
                 68 
                 59 
                 64 
                 69 
                 60 
               
               
                 nCohort Persistent 
                 27 
                 15 
                 21 
                 22 
                 13 
                 18 
                 20 
                 12 
                 17 
               
               
                 Cutoff Quartile 2 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
               
               
                 Sensitivity 
                 78% 
                 73% 
                 76% 
                 77% 
                 77% 
                 72% 
                 75% 
                 75% 
                 76% 
               
               
                 Specificity 
                 26% 
                 24% 
                 25% 
                 26% 
                 25% 
                 24% 
                 25% 
                 25% 
                 25% 
               
               
                 Cutoff Quartile 3 
                  9.66 
                  9.75 
                  9.75 
                  9.66 
                  9.75 
                  9.75 
                  9.66 
                  9.75 
                  9.75 
               
               
                 Sensitivity 
                 56% 
                 53% 
                 57% 
                 55% 
                 54% 
                 56% 
                 60% 
                 58% 
                 59% 
               
               
                 Specificity 
                 53% 
                 50% 
                 52% 
                 52% 
                 50% 
                 51% 
                 53% 
                 51% 
                 52% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
               
               
                 Sensitivity 
                 33% 
                 33% 
                 38% 
                 32% 
                 31% 
                 39% 
                 35% 
                 33% 
                 41% 
               
               
                 Specificity 
                 79% 
                 76% 
                 79% 
                 77% 
                 75% 
                 78% 
                 78% 
                 75% 
                 78% 
               
               
                 OR Quartile 2 
                  1.25 
                  0.880 
                  1.07 
                  1.18 
                  1.11 
                  0.809 
                  1.00 
                  0.981 
                  1.08 
               
               
                 p Value 
                  0.69 
                  0.84 
                  0.91 
                  0.77 
                  0.88 
                  0.73 
                  1.0 
                  0.98 
                  0.90 
               
               
                 Lower limit of 95% CI 
                  0.424 
                  0.246 
                  0.330 
                  0.375 
                  0.273 
                  0.245 
                  0.314 
                  0.238 
                  0.306 
               
               
                 Upper limit of 95% CI 
                  3.69 
                  3.15 
                  3.44 
                  3.73 
                  4.52 
                  2.67 
                  3.19 
                  4.04 
                  3.83 
               
               
                 OR Quartile 3 
                  1.39 
                  1.14 
                  1.43 
                  1.28 
                  1.17 
                  1.29 
                  1.70 
                  1.44 
                  1.53 
               
               
                 p Value 
                  0.48 
                  0.82 
                  0.49 
                  0.62 
                  0.80 
                  0.63 
                  0.31 
                  0.56 
                  0.45 
               
               
                 Lower limit of 95% CI 
                  0.553 
                  0.372 
                  0.521 
                  0.482 
                  0.355 
                  0.448 
                  0.613 
                  0.417 
                  0.513 
               
               
                 Upper limit of 95% CI 
                  3.49 
                  3.51 
                  3.94 
                  3.40 
                  3.83 
                  3.73 
                  4.72 
                  4.98 
                  4.54 
               
               
                 OR Quartile 4 
                  1.88 
                  1.56 
                  2.26 
                  1.60 
                  1.33 
                  2.25 
                  1.92 
                  1.53 
                  2.53 
               
               
                 p Value 
                  0.23 
                  0.47 
                  0.14 
                  0.39 
                  0.66 
                  0.16 
                  0.24 
                  0.53 
                  0.11 
               
               
                 Lower limit of 95% CI 
                  0.674 
                  0.465 
                  0.760 
                  0.545 
                  0.364 
                  0.727 
                  0.644 
                  0.409 
                  0.806 
               
               
                 Upper limit of 95% CI 
                  5.21 
                  5.25 
                  6.70 
                  4.70 
                  4.89 
                  6.97 
                  5.74 
                  5.72 
                  7.95 
               
               
                   
               
            
           
         
       
     
     Example 15. Use of C-C Motif Chemokine 16 for Evaluating Renal Status in Patients Admitted to the ICU: Persistent at RIFLE I or F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. C-C motif chemokine 16 is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output. Two cohorts are defined to represent a “persistent” and a “non-persistent” population. “Persistent” indicates those patients whose minimum RIFLE stage during a period of 24, 48 or 72 hours is injury (I) or failure (F) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. “Non-persistent” indicates those patients who are not persistent at injury (I) or failure (F) and whose minimum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0) or risk of injury (R) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. If a patient dies after injury (I) or failure (F) or is placed on renal replacement therapy (RRT) at any time from sample collection to 24, 48, 72, 96 or 168 hours after sample collection, the patient is considered “persistent”. 
     The ability to distinguish the “persistent” and “non-persistent” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 15.1 
               
             
            
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
            
           
           
               
               
            
               
                   
                 RIFLE criteria. 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0100 
                  0.0299 
                  0.00924 
                  0.0411 
                  0.0100 
                  0.0352 
               
               
                 Average 
                  0.0164 
                  0.108 
                  0.0204 
                  0.162 
                  0.0221 
                  0.182 
               
               
                 Stdev 
                  0.0191 
                  0.442 
                  0.0311 
                  0.568 
                  0.0317 
                  0.615 
               
               
                 p (t-test) 
                   
                  0.20 
                   
                  0.065 
                   
                  0.046 
               
               
                 Min 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 1.60E−5 
               
               
                 Max 
                  0.0865 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 38 
                 45 
                 56 
                 27 
                 60 
                 23 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0108 
                  0.0460 
                  0.0133 
                  0.0329 
                  0.0146 
                  0.0265 
               
               
                 Average 
                  0.0193 
                  0.190 
                  0.0239 
                  0.211 
                  0.0312 
                  0.216 
               
               
                 Stdev 
                  0.0233 
                  0.613 
                  0.0316 
                  0.676 
                  0.0566 
                  0.737 
               
               
                 p (t-test) 
                   
                  0.038 
                   
                  0.032 
                   
                  0.046 
               
               
                 Min 
                 4.13E−6 
                 1.26E−5 
                 4.13E−6 
                 1.26E−5 
                 4.13E−6 
                 1.26E−5 
               
               
                 Max 
                  0.106 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 57 
                 23 
                 61 
                 19 
                 64 
                 16 
               
            
           
           
               
            
               
                 UO Only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0170 
                  0.0153 
                  0.0170 
                  0.0153 
                  0.0170 
               
               
                 Average 
                  0.0264 
                  0.104 
                  0.0264 
                  0.141 
                  0.0264 
                  0.149 
               
               
                 Stdev 
                  0.0352 
                  0.453 
                  0.0342 
                  0.550 
                  0.0337 
                  0.570 
               
               
                 p (t-test) 
                   
                  0.32 
                   
                  0.15 
                   
                  0.13 
               
               
                 Min 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 35 
                 43 
                 49 
                 29 
                 51 
                 27 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.65 
                  0.75 
                  0.54 
                  0.76 
                  0.69 
                  0.56 
                  0.75 
                  0.63 
                  0.56 
               
               
                 SE 
                  0.060 
                  0.065 
                  0.066 
                  0.060 
                  0.074 
                  0.068 
                  0.065 
                  0.082 
                  0.069 
               
               
                 p Value 
                  0.0094 
                 1.3E-4 
                  0.50 
                 2.1E-5 
                  0.0086 
                  0.38 
                 1.6E-4 
                  0.12 
                  0.43 
               
               
                 nCohort Non-persistent 
                 38 
                 57 
                 35 
                 56 
                 61 
                 49 
                 60 
                 64 
                 51 
               
               
                 nCohort Persistent 
                 45 
                 23 
                 43 
                 27 
                 19 
                 29 
                 23 
                 16 
                 27 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 76% 
                 91% 
                 72% 
                 93% 
                 89% 
                 76% 
                 96% 
                 88% 
                 74% 
               
               
                 Specificity 
                 24% 
                 32% 
                 20% 
                 32% 
                 30% 
                 24% 
                 32% 
                 28% 
                 24% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                  62% 
                  74% 
                  53% 
                  78% 
                  74% 
                  52% 
                  78% 
                  69% 
                  52% 
               
               
                 Specificity 
                  63% 
                  60% 
                  54% 
                  62% 
                  57% 
                  51% 
                  60% 
                  55% 
                  51% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 38% 
                 52% 
                 30% 
                 48% 
                 47% 
                 34% 
                 43% 
                 38% 
                 33% 
               
               
                 Specificity 
                 87% 
                 86% 
                 77% 
                 84% 
                 82% 
                 78% 
                 80% 
                 78% 
                 76% 
               
               
                 OR Quartile 2 
                  0.959 
                  4.85 
                  0.646 
                  5.92 
                  3.56 
                  1.02 
                  10.2 
                  2.74 
                  0.879 
               
               
                 p Value 
                  0.94 
                  0.047 
                  0.42 
                  0.024 
                  0.11 
                  0.97 
                  0.028 
                  0.21 
                  0.81 
               
               
                 Lower limit of 95% CI 
                  0.349 
                  1.02 
                  0.223 
                  1.26 
                  0.744 
                  0.349 
                  1.28 
                  0.565 
                  0.299 
               
               
                 Upper limit of 95% CI 
                  2.64 
                  22.9 
                  1.87 
                  27.8 
                  17.0 
                  2.98 
                  81.3 
                  13.3 
                  2.58 
               
               
                 OR Quartile 3 
                  2.82 
                  4.19 
                  1.37 
                  5.83 
                  3.77 
                  1.12 
                  5.40 
                  2.66 
                  1.12 
               
               
                 p Value 
                  0.023 
                  0.0087 
                  0.50 
                  0.0011 
                  0.023 
                  0.81 
                  0.0031 
                  0.10 
                  0.81 
               
               
                 Lower limit of 95% CI 
                  1.16 
                  1.44 
                  0.558 
                  2.03 
                  1.21 
                  0.445 
                  1.77 
                  0.827 
                  0.440 
               
               
                 Upper limit of 95% CI 
                  6.90 
                  12.2 
                  3.34 
                  16.8 
                  11.8 
                  2.80 
                  16.5 
                  8.52 
                  2.85 
               
               
                 OR Quartile 4 
                  4.01 
                  6.68 
                  1.46 
                  4.85 
                  4.09 
                  1.82 
                  3.08 
                  2.14 
                  1.62 
               
               
                 p Value 
                  0.015 
                  7.8E-4 
                  0.47 
                  0.0029 
                  0.013 
                  0.25 
                  0.034 
                  0.20 
                  0.36 
               
               
                 Lower limit of 95% CI 
                  1.31 
                  2.21 
                  0.526 
                  1.72 
                  1.35 
                  0.657 
                  1.09 
                  0.663 
                  0.581 
               
               
                 Upper limit of 95% CI 
                 12.2 
                 20.2 
                  4.07 
                 13.7 
                 12.4 
                  5.03 
                  8.70 
                  6.92 
                  4.55 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0137 
                  0.0182 
                  0.0100 
                  0.0329 
                  0.0112 
                  0.0305 
               
               
                 Average 
                  0.0175 
                  0.0939 
                  0.0209 
                  0.135 
                  0.0228 
                  0.147 
               
               
                 Stdev 
                  0.0194 
                  0.408 
                  0.0322 
                  0.515 
                  0.0328 
                  0.549 
               
               
                 p (t-test) 
                   
                  0.31 
                   
                  0.12 
                   
                  0.099 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.0865 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 30 
                 53 
                 50 
                 33 
                 54 
                 29 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0133 
                  0.0305 
                  0.0137 
                  0.0302 
                  0.0146 
                  0.0262 
               
               
                 Average 
                  0.0199 
                  0.163 
                  0.0245 
                  0.184 
                  0.0316 
                  0.195 
               
               
                 Stdev 
                  0.0238 
                  0.568 
                  0.0322 
                  0.630 
                  0.0575 
                  0.695 
               
               
                 p (t-test) 
                   
                  0.069 
                   
                  0.056 
                   
                 0.068 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 1.26E−5 
               
               
                 Max 
                  0.106 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 53 
                 27 
                 58 
                 22 
                 62 
                 18 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0170 
                  0.0147 
                  0.0189 
                  0.0147 
                  0.0189 
               
               
                 Average 
                  0.0280 
                  0.0933 
                  0.0268 
                  0.124 
                  0.0268 
                  0.130 
               
               
                 Stdev 
                  0.0374 
                  0.425 
                  0.0354 
                  0.509 
                  0.0349 
                  0.524 
               
               
                 p (t-test) 
                   
                  0.41 
                   
                  0.21 
                   
                  0.19 
               
               
                 Min 
                 6.68E−6 
                 4.13E-6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 29 
                 49 
                 44 
                 34 
                 46 
                 32 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.60 
                  0.69 
                  0.52 
                  0.71 
                  0.65 
                  0.55 
                  0.69 
                  0.62 
                  0.55 
               
               
                 SE 
                  0.063 
                  0.065 
                  0.068 
                  0.060 
                  0.072 
                  0.066 
                  0.063 
                  0.078 
                  0.067 
               
               
                 p Value 
                  0.10 
                  0.0034 
                  0.78 
                 5.5E−4 
                  0.038 
                  0.43 
                  0.0032 
                  0.13 
                  0.48 
               
               
                 nCohort Non-persistent 
                 30 
                 53 
                 29 
                 50 
                 58 
                 44 
                 54 
                 62 
                 46 
               
               
                 nCohort Persistent 
                 53 
                 27 
                 49 
                 33 
                 22 
                 34 
                 29 
                 18 
                 32 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 75% 
                 89% 
                 71% 
                 91% 
                 86% 
                 76% 
                 93% 
                 89% 
                 75% 
               
               
                 Specificity 
                 23% 
                 32% 
                 17% 
                 34% 
                 29% 
                 25% 
                 33% 
                 29% 
                 24% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 57% 
                  67% 
                 53% 
                 70% 
                 68% 
                 53% 
                 69% 
                 67% 
                 53% 
               
               
                 Specificity 
                 60% 
                  58% 
                 55% 
                 62% 
                 57% 
                 52% 
                 59% 
                 55% 
                 52% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 34% 
                 44% 
                 29% 
                 42% 
                 41% 
                 32% 
                  38% 
                 33% 
                 31% 
               
               
                 Specificity 
                 87% 
                 85% 
                 76% 
                 84% 
                 81% 
                 77% 
                  80% 
                 77% 
                 76% 
               
               
                 OR Quartile 2 
                  0.936 
                  3.78 
                  0.521 
                  5.15 
                  2.63 
                  1.08 
                  6.75 
                  3.27 
                  0.943 
               
               
                 p Value 
                  0.90 
                  0.050 
                  0.26 
                  0.015 
                  0.16 
                  0.88 
                  0.015 
                  0.14 
                  0.91 
               
               
                 Lower limit of 95% CI 
                  0.327 
                  0.997 
                  0.166 
                  1.37 
                  0.686 
                  0.381 
                  1.44 
                  0.682 
                  0.330 
               
               
                 Upper limit of 95% CI 
                  2.68 
                 14.3 
                  1.64 
                  19.3 
                 10.1 
                  3.08 
                  31.6 
                  15.7 
                  2.69 
               
               
                 OR Quartile 3 
                  1.96 
                  2.82 
                  1.39 
                  3.75 
                  2.83 
                  1.23 
                  3.23 
                  2.43 
                  1.24 
               
               
                 p Value 
                  0.15 
                  0.036 
                  0.48 
                  0.0057 
                  0.049 
                  0.65 
                  0.016 
                  0.11 
                  0.65 
               
               
                 Lower limit of 95% CI 
                  0.787 
                  1.07 
                  0.553 
                  1.47 
                  1.00 
                  0.503 
                  1.24 
                  0.808 
                  0.501 
               
               
                 Upper limit of 95% CI 
                  4.86 
                  7.43 
                  3.50 
                  9.57 
                  7.98 
                  3.02 
                  8.41 
                  7.30 
                  3.05 
               
               
                 OR Quartile 4 
                  3.34 
                  4.50 
                  1.26 
                  3.87 
                  2.96 
                  1.63 
                  2.39 
                  1.71 
                  1.45 
               
               
                 p Value 
                  0.048 
                  0.0058 
                  0.67 
                  0.0096 
                  0.048 
                  0.34 
                  0.088 
                  0.36 
                  0.47 
               
               
                 Lower limit of 95% CI 
                  1.01 
                  1.55 
                  0.439 
                  1.39 
                  1.01 
                  0.594 
                  0.878 
                  0.545 
                  0.527 
               
               
                 Upper limit of 95% CI 
                 11.1 
                 13.1 
                  3.60 
                 10.8 
                  8.66 
                  4.45 
                  6.50 
                  5.40 
                  3.97 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0177 
                  0.0112 
                  0.0305 
                  0.0124 
                  0.0299 
               
               
                 Average 
                  0.0179 
                  0.0923 
                  0.0216 
                  0.128 
                  0.0235 
                  0.138 
               
               
                 Stdev 
                  0.0197 
                  0.405 
                  0.0327 
                  0.500 
                  0.0332 
                  0.532 
               
               
                 p (t-test) 
                   
                  0.33 
                   
                  0.15 
                   
                  0.12 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.0865 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 29 
                 54 
                 48 
                 35 
                 52 
                 31 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0137 
                  0.0302 
                  0.0142 
                  0.0299 
                  0.0151 
                  0.0225 
               
               
                 Average 
                  0.0202 
                  0.158 
                  0.0248 
                  0.176 
                  0.0320 
                  0.185 
               
               
                 Stdev 
                  0.0240 
                  0.558 
                  0.0324 
                  0.616 
                  0.0579 
                  0.677 
               
               
                 p (t-test) 
                   
                  0.079 
                   
                  0.066 
                   
                  0.081 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 4.13E-6 
                 1.26E−5 
               
               
                 Max 
                  0.106 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 52 
                 28 
                 57 
                 23 
                 61 
                 19 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0170 
                  0.0153 
                  0.0170 
                  0.0153 
                  0.0170 
               
               
                 Average 
                  0.0280 
                  0.0933 
                  0.0274 
                  0.120 
                  0.0274 
                  0.126 
               
               
                 Stdev 
                  0.0374 
                  0.425 
                  0.0356 
                  0.502 
                  0.0351 
                  0.517 
               
               
                 p (t-test) 
                   
                  0.41 
                   
                  0.23 
                   
                  0.21 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 29 
                 49 
                 43 
                 35 
                 45 
                 33 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.60 
                  0.68 
                  0.52 
                  0.68 
                  0.64 
                  0.54 
                  0.66 
                  0.60 
                  0.53 
               
               
                 SE 
                  0.064 
                  0.065 
                  0.068 
                  0.060 
                  0.071 
                  0.066 
                  0.064 
                  0.077 
                  0.067 
               
               
                 p Value 
                  0.13 
                  0.0060 
                  0.78 
                  0.0029 
                  0.057 
                  0.57 
                  0.013 
                  0.17 
                  0.63 
               
               
                 nCohort Non-persistent 
                 29 
                 52 
                 29 
                 48 
                 57 
                 43 
                 52 
                 61 
                 45 
               
               
                 nCohort Persistent 
                 54 
                 28 
                 49 
                 35 
                 23 
                 35 
                 31 
                 19 
                 33 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 76% 
                 89% 
                 71% 
                 89% 
                 87% 
                 74% 
                 90% 
                 89% 
                 73% 
               
               
                 Specificity 
                 24% 
                 33% 
                 17% 
                 33% 
                 30% 
                 23% 
                 33% 
                 30% 
                 22% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 56% 
                 64% 
                 53% 
                 66% 
                 65% 
                 51% 
                 65% 
                 63% 
                 52% 
               
               
                 Specificity 
                 59% 
                 58% 
                 55% 
                 60% 
                 56% 
                 51% 
                 58% 
                 54% 
                 51% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 33% 
                 43% 
                 29% 
                 40% 
                 39% 
                 31% 
                 35% 
                 32% 
                 30% 
               
               
                 Specificity 
                 86% 
                 85% 
                 76% 
                 83% 
                 81% 
                 77% 
                 79% 
                 77% 
                 76% 
               
               
                 OR Quartile 2 
                  1.00 
                  4.05 
                  0.521 
                  3.88 
                  2.83 
                  0.875 
                  4.53 
                  3.56 
                  0.762 
               
               
                 p Value 
                  0.99 
                  0.039 
                  0.26 
                  0.027 
                  0.13 
                  0.80 
                  0.025 
                  0.11 
                  0.61 
               
               
                 Lower limit of 95% CI 
                  0.349 
                  1.07 
                  0.166 
                  1.16 
                  0.742 
                  0.310 
                  1.21 
                  0.744 
                  0.269 
               
               
                 Upper limit of 95% CI 
                  2.88 
                  15.3 
                  1.64 
                  12.9 
                  10.8 
                  2.47 
                  17.0 
                  17.0 
                  2.15 
               
               
                 OR Quartile 3 
                  1.77 
                  2.45 
                  1.39 
                  2.93 
                  2.40 
                  1.11 
                  2.48 
                  2.02 
                  1.11 
               
               
                 p Value 
                  0.22 
                  0.064 
                  0.48 
                  0.020 
                  0.088 
                  0.82 
                  0.053 
                  0.19 
                  0.82 
               
               
                 Lower limit of 95% CI 
                  0.710 
                  0.950 
                  0.553 
                  1.18 
                  0.879 
                  0.454 
                  0.989 
                  0.700 
                  0.452 
               
               
                 Upper limit of 95% CI 
                  4.41 
                  6.34 
                  3.50 
                  7.24 
                  6.56 
                  2.71 
                  6.21 
                  5.83 
                  2.73 
               
               
                 OR Quartile 4 
                  3.12 
                  4.12 
                  1.26 
                  3.33 
                  2.69 
                  1.51 
                  2.05 
                  1.55 
                  1.34 
               
               
                 p Value 
                  0.062 
                  0.0089 
                  0.67 
                  0.020 
                  0.069 
                  0.42 
                  0.16 
                  0.45 
                  0.56 
               
               
                 Lower limit of 95% CI 
                  0.944 
                  1.43 
                  0.439 
                  1.21 
                  0.927 
                  0.554 
                  0.760 
                  0.497 
                  0.491 
               
               
                 Upper limit of 95% CI 
                 10.4 
                 11.9 
                  3.60 
                  9.21 
                  7.80 
                  4.13 
                  5.53 
                  4.83 
                  3.68 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0177 
                  0.0108 
                  0.0302 
                  0.0100 
                  0.0305 
               
               
                 Average 
                  0.0155 
                  0.0908 
                  0.0208 
                  0.120 
                  0.0213 
                  0.128 
               
               
                 Stdev 
                  0.0151 
                  0.397 
                  0.0322 
                  0.481 
                  0.0328 
                  0.500 
               
               
                 p (t-test) 
                   
                  0.33 
                   
                  0.17 
                   
                  0.14 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.0518 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 27 
                 56 
                 45 
                 38 
                 48 
                 35 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0125 
                  0.0302 
                  0.0142 
                  0.0299 
                  0.0146 
                  0.0262 
               
               
                 Average 
                  0.0199 
                  0.149 
                  0.0247 
                  0.164 
                  0.0318 
                  0.164 
               
               
                 Stdev 
                  0.0243 
                  0.540 
                  0.0329 
                  0.591 
                  0.0593 
                  0.629 
               
               
                 p (t-test) 
                   
                  0.094 
                   
                  0.083 
                   
                  0.11 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 1.26E−5 
               
               
                 Max 
                  0.106 
                  2.98 
                  0.151 
                  2.98 
                  0.399 
                  2.98 
               
               
                 n (Patient) 
                 50 
                 30 
                 55 
                 25 
                 58 
                 22 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0170 
                  0.0153 
                  0.0170 
                  0.0147 
                  0.0189 
               
               
                 Average 
                  0.0264 
                  0.0916 
                  0.0263 
                  0.112 
                  0.0257 
                  0.115 
               
               
                 Stdev 
                  0.0370 
                  0.416 
                  0.0357 
                  0.475 
                  0.0354 
                  0.481 
               
               
                 p (t-test) 
                   
                  0.42 
                   
                  0.27 
                   
                  0.25 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 27 
                 51 
                 39 
                 39 
                 40 
                 38 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.62 
                  0.68 
                  0.54 
                  0.68 
                  0.64 
                  0.56 
                  0.70 
                  0.62 
                  0.57 
               
               
                 SE 
                  0.064 
                  0.063 
                  0.068 
                  0.059 
                  0.069 
                  0.065 
                  0.059 
                  0.073 
                  0.065 
               
               
                 p Value 
                  0.061 
                  0.0041 
                  0.55 
                  0.0020 
                  0.045 
                  0.37 
                 8.8E−4 
                  0.089 
                  0.27 
               
               
                 nCohort Non-persistent 
                 27 
                 50 
                 27 
                 45 
                 55 
                 39 
                 48 
                 58 
                 40 
               
               
                 nCohort Persistent 
                 56 
                 30 
                 51 
                 38 
                 25 
                 39 
                 35 
                 22 
                 38 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 77% 
                 90% 
                 73% 
                 89% 
                 88% 
                 77% 
                 91% 
                 91% 
                 76% 
               
               
                 Specificity 
                 26% 
                 34% 
                 19% 
                 36% 
                 31% 
                 26% 
                 35% 
                 31% 
                 25% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 55% 
                 63% 
                 53% 
                 63% 
                 64% 
                 51% 
                 66% 
                 64% 
                 53% 
               
               
                 Specificity 
                 59% 
                 58% 
                 56% 
                 60% 
                 56% 
                 51% 
                 60% 
                 55% 
                 52% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 34% 
                 40% 
                 29% 
                 39% 
                 36% 
                 33% 
                 40% 
                 32% 
                 34% 
               
               
                 Specificity 
                 89% 
                 84% 
                 78% 
                 84% 
                 80% 
                 79% 
                 83% 
                 78% 
                 80% 
               
               
                 OR Quartile 2 
                  1.16 
                  4.64 
                  0.601 
                  4.69 
                  3.28 
                  1.15 
                  5.85 
                  4.50 
                  1.07 
               
               
                 p Value 
                  0.79 
                  0.024 
                  0.38 
                  0.012 
                  0.081 
                  0.79 
                  0.0089 
                  0.058 
                  0.89 
               
               
                 Lower limit of 95% CI 
                  0.401 
                  1.23 
                  0.190 
                  1.41 
                  0.863 
                  0.408 
                  1.56 
                  0.949 
                  0.381 
               
               
                 Upper limit of 95% CI 
                  3.34 
                 17.5 
                  1.90 
                 15.6 
                 12.5 
                  3.24 
                  22.0 
                  21.3 
                  3.02 
               
               
                 OR Quartile 3 
                  1.80 
                  2.39 
                  1.41 
                  2.57 
                  2.30 
                  1.11 
                  2.93 
                  2.15 
                  1.23 
               
               
                 p Value 
                  0.21 
                  0.067 
                  0.48 
                  0.037 
                  0.095 
                  0.82 
                  0.020 
                  0.14 
                  0.65 
               
               
                 Lower limit of 95% CI 
                  0.711 
                  0.940 
                  0.551 
                  1.06 
                  0.866 
                  0.456 
                  1.18 
                  0.784 
                  0.505 
               
               
                 Upper limit of 95% CI 
                  4.58 
                  6.05 
                  3.59 
                  6.25 
                  6.09 
                  2.69 
                  7.24 
                  5.92 
                  2.99 
               
               
                 OR Quartile 4 
                  4.11 
                  3.50 
                  1.46 
                  3.54 
                  2.25 
                  1.94 
                  3.33 
                  1.62 
                  2.08 
               
               
                 p Value 
                  0.036 
                  0.020 
                  0.50 
                  0.017 
                  0.13 
                  0.21 
                  0.020 
                  0.39 
                  0.16 
               
               
                 Lower limit of 95% CI 
                  1.10 
                  1.22 
                  0.491 
                  1.26 
                  0.787 
                  0.696 
                  1.21 
                  0.544 
                  0.747 
               
               
                 Upper limit of 95% CI 
                 15.4 
                 10.0 
                  4.33 
                  9.98 
                  6.43 
                  5.39 
                  9.21 
                  4.80 
                  5.79 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0142 
                  0.0177 
                  0.0108 
                  0.0262 
                  0.0100 
                  0.0299 
               
               
                 Average 
                  0.0159 
                  0.0880 
                  0.0213 
                  0.115 
                  0.0218 
                  0.122 
               
               
                 Stdev 
                  0.0154 
                  0.391 
                  0.0328 
                  0.469 
                  0.0334 
                  0.487 
               
               
                 p (t-test) 
                   
                  0.36 
                   
                  0.20 
                   
                  0.17 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.0518 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 25 
                 58 
                 43 
                 40 
                 46 
                 37 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0108 
                  0.0305 
                  0.0129 
                  0.0302 
                  0.0129 
                  0.0302 
               
               
                 Average 
                  0.0185 
                  0.147 
                  0.0236 
                  0.161 
                  0.0243 
                  0.171 
               
               
                 Stdev 
                  0.0225 
                  0.531 
                  0.0321 
                  0.580 
                  0.0327 
                  0.603 
               
               
                 p (t-test) 
                   
                  0.094 
                   
                  0.084 
                   
                  0.071 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 4.13E−6 
                 1.26E−5 
               
               
                 Max 
                  0.106 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 49 
                 31 
                 54 
                 26 
                 56 
                 24 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  0.0147 
                  0.0163 
                  0.0157 
                  0.0151 
                  0.0153 
                  0.0170 
               
               
                 Average 
                  0.0274 
                  0.0898 
                  0.0277 
                  0.106 
                  0.0264 
                  0.112 
               
               
                 Stdev 
                  0.0373 
                  0.413 
                  0.0361 
                  0.464 
                  0.0356 
                  0.475 
               
               
                 p (t-test) 
                   
                  0.45 
                   
                  0.31 
                   
                  0.27 
               
               
                 Min 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
                 6.68E−6 
                 4.13E−6 
               
               
                 Max 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
                  0.151 
                  2.98 
               
               
                 n (Patient) 
                 26 
                 52 
                 37 
                 41 
                 39 
                 39 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.61 
                  0.70 
                  0.52 
                  0.67 
                  0.66 
                  0.52 
                  0.68 
                  0.67 
                  0.55 
               
               
                 SE 
                  0.066 
                  0.062 
                  0.069 
                  0.060 
                  0.067 
                  0.066 
                  0.060 
                  0.069 
                  0.065 
               
               
                 p Value 
                  0.11 
                  0.0011 
                  0.80 
                  0.0055 
                  0.018 
                  0.80 
                  0.0028 
                  0.013 
                  0.44 
               
               
                 nCohort Non-persistent 
                 25 
                 49 
                 26 
                 43 
                 54 
                 37 
                 46 
                 56 
                 39 
               
               
                 nCohort Persistent 
                 58 
                 31 
                 52 
                 40 
                 26 
                 41 
                 37 
                 24 
                 39 
               
               
                 Cutoff Quartile 2 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
                  0.00202 
                  0.00161 
                  0.00202 
               
               
                 Sensitivity 
                 76% 
                 90% 
                 71% 
                 88% 
                 88% 
                 73% 
                 89% 
                 92% 
                 74% 
               
               
                 Specificity 
                 24% 
                 35% 
                 15% 
                 35% 
                 31% 
                 22% 
                 35% 
                 32% 
                 23% 
               
               
                 Cutoff Quartile 3 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
                  0.0157 
                  0.0165 
                  0.0155 
               
               
                 Sensitivity 
                 55% 
                 65% 
                 52% 
                 62% 
                 65% 
                 49% 
                 65% 
                 67% 
                 51% 
               
               
                 Specificity 
                 60% 
                 59% 
                 54% 
                 60% 
                 57% 
                 49% 
                 61% 
                 57% 
                 51% 
               
               
                 Cutoff Quartile 4 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
                  0.0427 
                  0.0435 
                  0.0427 
               
               
                 Sensitivity 
                 33% 
                 42% 
                 29% 
                 38% 
                 38% 
                 32% 
                 38% 
                 38% 
                 33% 
               
               
                 Specificity 
                 88% 
                 86% 
                 77% 
                 84% 
                 81% 
                 78% 
                 83% 
                 80% 
                 79% 
               
               
                 OR Quartile 2 
                  0.992 
                  4.96 
                  0.448 
                  3.75 
                  3.52 
                  0.752 
                  4.40 
                  5.21 
                  0.870 
               
               
                 p Value 
                  0.99 
                  0.018 
                  0.20 
                  0.022 
                  0.064 
                  0.59 
                  0.016 
                  0.037 
                  0.79 
               
               
                 Lower limit of 95% CI 
                  0.331 
                  1.31 
                  0.132 
                  1.21 
                  0.929 
                  0.265 
                  1.32 
                  1.10 
                  0.309 
               
               
                 Upper limit of 95% CI 
                  2.97 
                 18.7 
                  1.52 
                 11.6 
                 13.4 
                  2.14 
                  14.6 
                  24.6 
                  2.45 
               
               
                 OR Quartile 3 
                  1.85 
                  2.64 
                  1.26 
                  2.55 
                  2.55 
                  0.902 
                  2.87 
                  2.67 
                  1.11 
               
               
                 p Value 
                  0.21 
                  0.041 
                  0.63 
                  0.038 
                  0.059 
                  0.82 
                  0.021 
                  0.055 
                  0.82 
               
               
                 Lower limit of 95% CI 
                  0.712 
                  1.04 
                  0.490 
                  1.05 
                  0.964 
                  0.371 
                  1.17 
                  0.981 
                  0.456 
               
               
                 Upper limit of 95% CI 
                  4.79 
                  6.69 
                  3.24 
                  6.18 
                  6.73 
                  2.20 
                  7.05 
                  7.25 
                  2.69 
               
               
                 OR Quartile 4 
                  3.57 
                  4.33 
                  1.35 
                  3.09 
                  2.75 
                  1.68 
                  2.89 
                  2.45 
                  1.94 
               
               
                 p Value 
                  0.060 
                  0.0073 
                  0.59 
                  0.032 
                  0.058 
                  0.32 
                  0.040 
                  0.096 
                  0.21 
               
               
                 Lower limit of 95% CI 
                  0.950 
                  1.48 
                  0.453 
                  1.10 
                  0.965 
                  0.605 
                  1.05 
                  0.853 
                  0.696 
               
               
                 Upper limit of 95% CI 
                 13.4 
                 12.7 
                  4.03 
                  8.66 
                  7.83 
                  4.68 
                  7.95 
                  7.06 
                  5.39 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
                 Non-persistent 
                   
               
               
                   
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
                 Cohort 
                 Persistent Cohort 
               
               
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  7.72 
                 10.6 
                  8.48 
                 10.6 
                  8.56 
                 10.5 
               
               
                 Average 
                 10.3 
                 13.8 
                 10.8 
                 14.6 
                 10.9 
                 15.2 
               
               
                 Stdev 
                  7.18 
                  9.68 
                  6.82 
                 11.3 
                  6.79 
                 12.0 
               
               
                 p (t-test) 
                   
                  0.067 
                   
                  0.059 
                   
                  0.040 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
                 30.8 
                 38.9 
               
               
                 n (Patient) 
                 41 
                 43 
                 56 
                 28 
                 61 
                 23 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  8.48 
                 12.0 
                  9.00 
                 10.6 
                  9.75 
                 10.0 
               
               
                 Average 
                 11.6 
                 13.4 
                 12.1 
                 12.3 
                 12.3 
                 11.6 
               
               
                 Stdev 
                  8.72 
                  8.96 
                  8.75 
                  9.05 
                  8.71 
                  9.21 
               
               
                 p (t-test) 
                   
                 0.43 
                   
                 0.93 
                   
                 0.78 
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
               
               
                 n (Patient) 
                 58 
                 23 
                 61 
                 20 
                 63 
                 18 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                  8.41 
                 10.5 
                  8.89 
                 11.3 
                  8.89 
                 11.3 
               
               
                 Average 
                 11.3 
                 13.0 
                 11.2 
                 13.8 
                 11.2 
                 14.0 
               
               
                 Stdev 
                  8.07 
                  8.97 
                  7.59 
                  9.90 
                  7.48 
                 10.2 
               
               
                 p (t-test) 
                   
                  0.37 
                   
                  0.20 
                   
                  0.18 
               
               
                 Min 
                  2.64 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
               
               
                 Max 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
                 37.2 
                 38.9 
               
               
                 n (Patient) 
                 37 
                 40 
                 49 
                 28 
                 51 
                 26 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Persistence Period Duration (hr) 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.62 
                  0.58 
                  0.57 
                  0.59 
                  0.52 
                  0.57 
                  0.59 
                  0.49 
                  0.57 
               
               
                 SE 
                  0.061 
                  0.072 
                  0.065 
                  0.067 
                  0.075 
                  0.069 
                  0.072 
                  0.078 
                  0.070 
               
               
                 p Value 
                  0.043 
                  0.25 
                  0.27 
                  0.21 
                  0.74 
                  0.30 
                  0.23 
                  0.87 
                  0.34 
               
               
                 nCohort Non-persistent 
                 41 
                 58 
                 37 
                 56 
                 61 
                 49 
                 61 
                 63 
                 51 
               
               
                 nCohort Persistent 
                 43 
                 23 
                 40 
                 28 
                 20 
                 28 
                 23 
                 18 
                 26 
               
               
                 Cutoff Quartile 2 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
                  6.19 
                  6.19 
                  6.24 
               
               
                 Sensitivity 
                 81% 
                 83% 
                 80% 
                 79% 
                 80% 
                 79% 
                 78% 
                 78% 
                 77% 
               
               
                 Specificity 
                 32% 
                 28% 
                 30% 
                 27% 
                 26% 
                 27% 
                 26% 
                 25% 
                 25% 
               
               
                 Cutoff Quartile 3 
                  9.66 
                  9.75 
                  9.75 
                  9.66 
                  9.75 
                  9.75 
                  9.66 
                  9.75 
                  9.75 
               
               
                 Sensitivity 
                 58% 
                 61% 
                 57% 
                 57% 
                 55% 
                 61% 
                 57% 
                 50% 
                 62% 
               
               
                 Specificity 
                 59% 
                 53% 
                 57% 
                 54% 
                 51% 
                 55% 
                 52% 
                 49% 
                 55% 
               
               
                 Cutoff Quartile 4 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
                 16.0 
                 15.9 
                 15.9 
               
               
                 Sensitivity 
                 33% 
                 35% 
                 30% 
                 36% 
                 25% 
                 36% 
                 39% 
                 22% 
                 35% 
               
               
                 Specificity 
                 83% 
                 78% 
                 78% 
                 80% 
                 74% 
                 80% 
                 80% 
                 73% 
                 78% 
               
               
                 OR Quartile 2 
                  2.03 
                  1.81 
                  1.69 
                  1.34 
                  1.42 
                  1.32 
                  1.28 
                  1.19 
                  1.14 
               
               
                 p Value 
                  0.17 
                  0.34 
                  0.32 
                  0.59 
                  0.58 
                  0.62 
                  0.67 
                  0.78 
                  0.82 
               
               
                 Lower limit of 95% CI 
                  0.739 
                  0.533 
                  0.594 
                  0.456 
                  0.414 
                  0.439 
                  0.408 
                  0.342 
                  0.376 
               
               
                 Upper limit of 95% CI 
                  5.58 
                  6.14 
                  4.82 
                  3.95 
                  4.89 
                  3.99 
                  4.02 
                  4.15 
                  3.46 
               
               
                 OR Quartile 3 
                  1.96 
                  1.79 
                  1.78 
                  1.54 
                  1.26 
                  1.90 
                  1.43 
                  0.969 
                  1.95 
               
               
                 p Value 
                  0.13 
                  0.25 
                  0.21 
                  0.36 
                  0.65 
                  0.18 
                  0.46 
                  0.95 
                  0.18 
               
               
                 Lower limit of 95% CI 
                  0.823 
                  0.668 
                  0.720 
                  0.617 
                  0.458 
                  0.738 
                  0.546 
                  0.340 
                  0.743 
               
               
                 Upper limit of 95% CI 
                  4.67 
                  4.78 
                  4.38 
                  3.84 
                  3.48 
                  4.88 
                  3.77 
                  2.76 
                  5.11 
               
               
                 OR Quartile 4 
                  2.34 
                  1.85 
                  1.55 
                  2.27 
                  0.938 
                  2.17 
                  2.62 
                  0.773 
                  1.93 
               
               
                 p Value 
                  0.11 
                  0.26 
                  0.40 
                  0.11 
                  0.91 
                  0.14 
                  0.071 
                  0.68 
                  0.22 
               
               
                 Lower limit of 95% CI 
                  0.834 
                  0.642 
                  0.552 
                  0.823 
                  0.293 
                  0.766 
                  0.920 
                  0.223 
                  0.675 
               
               
                 Upper limit of 95% CI 
                  6.59 
                  5.31 
                  4.37 
                  6.28 
                  3.00 
                  6.13 
                  7.49 
                  2.68 
                  5.49 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the 
               
               
                 “persistent” and “non-persistent” cohorts where persistence starts within 48 hours after sample collection  
               
               
                 and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only,  
               
               
                 or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  7.83 
                 10.5  
                  8.78 
                 10.2  
                  9.00 
                  9.91  
               
               
                 Average 
                 10.3  
                 13.2  
                 11.1  
                 13.5  
                 11.1  
                 13.8  
               
               
                 Stdev 
                  7.46 
                  9.25 
                  6.97 
                 10.7  
                  6.92 
                 11.2  
               
               
                 p (t-test) 
                   
                  0.15 
                   
                  0.21  
                   
                  0.18  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8  
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 32   
                 52   
                 50   
                 34    
                 55    
                 29    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.48 
                 12.0  
                  9.37 
                 10.5  
                  9.75 
                 10.0  
               
               
                 Average 
                 11.6  
                 13.2  
                 12.3  
                 11.8  
                 12.3  
                 11.6  
               
               
                 Stdev 
                  8.75 
                   
                  8.82 
                  8.84  
                  8.78 
                  8.95  
               
               
                 p (t-test) 
                   
                  0.46 
                   
                  0.82  
                   
                  0.75  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 38.9  
                 37.2  
                 38.9  
                 37.2  
                 38.9  
                 37.2  
               
               
                 n (Patient) 
                 54   
                 27   
                 58   
                 23    
                 61   
                 20    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.17 
                 10.6  
                  8.73 
                 12.0  
                  8.73 
                 12.0  
               
               
                 Average 
                 10.6  
                 13.2  
                 10.6  
                 14.2  
                 10.7  
                 14.3  
               
               
                 Stdev 
                  6.96 
                  9.33 
                  6.57 
                 10.4  
                  6.49 
                 10.6  
               
               
                 p (t-test) 
                   
                  0.19 
                   
                  0.071 
                   
                  0.065 
               
               
                 Min 
                  2.64 
                  1.32 
                  1.62 
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8  
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 30   
                 47   
                 44   
                 33    
                 46   
                 31    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.61     
                  0.57     
                  0.58     
                  0.54     
                  0.49     
                  0.58     
                  0.54     
                  0.48     
                  0.58     
               
               
                 SE 
                  0.062    
                  0.069    
                  0.066    
                  0.065    
                  0.072    
                  0.066    
                  0.067    
                  0.075    
                  0.067    
               
               
                 p Value 
                  0.092    
                  0.32     
                  0.21     
                  0.53     
                  0.90     
                  0.22     
                  0.60     
                  0.81     
                  0.25     
               
               
                 nCohort Non-persistent 
                 32       
                 54       
                 30       
                 50       
                 58       
                 44       
                 55       
                 61       
                 46       
               
               
                 nCohort Persistent 
                 52       
                 27       
                 47       
                 34       
                 23       
                 33       
                 29       
                 20       
                 31       
               
               
                 Cutoff Quartile 2 
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
               
               
                 Sensitivity 
                 79%    
                 78%    
                 79%    
                 76%    
                 74%    
                 79%    
                 76%    
                 75%    
                 77%    
               
               
                 Specificity 
                 31%    
                 26%    
                 30%    
                 26%    
                 24%    
                 27%    
                 25%    
                 25%    
                 26%    
               
               
                 Cutoff Quartile 3 
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
               
               
                 Sensitivity 
                 56%    
                 59%    
                 57%    
                 53%    
                 52%    
                 61%    
                 52%    
                 50%    
                 61%    
               
               
                 Specificity 
                 59%    
                 54%    
                 60%    
                 52%    
                 50%    
                 57%    
                 51%    
                 49%    
                 57%    
               
               
                 Cutoff Quartile 4 
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
               
               
                 Sensitivity 
                 31%    
                 37%    
                 30%    
                 32%    
                 26%    
                 36%    
                 34%    
                 25%    
                 35%    
               
               
                 Specificity 
                 84%    
                 80%    
                 80%    
                 80%    
                 74%    
                 82%    
                 80%    
                 74%    
                 80%    
               
               
                 OR Quartile 2 
                  1.69     
                  1.22     
                  1.59     
                  1.14     
                  0.902    
                  1.39     
                  1.07     
                  0.978    
                  1.21     
               
               
                 p Value 
                  0.30     
                  0.72     
                  0.39     
                  0.80     
                  0.85     
                  0.54     
                  0.89     
                  0.97     
                  0.73     
               
               
                 Lower limit of 95% CI 
                  0.623    
                  0.411    
                  0.556    
                  0.414    
                  0.298    
                  0.480    
                  0.378    
                  0.304    
                  0.416    
               
               
                 Upper limit of 95% CI 
                  4.61     
                  3.65     
                  4.52     
                  3.15     
                  2.73     
                  4.05     
                  3.05     
                  3.15     
                  3.52     
               
               
                 OR Quartile 3 
                  1.84     
                  1.69     
                  2.02     
                  1.22     
                  1.09     
                  2.02     
                  1.11     
                  0.968    
                  2.06     
               
               
                 p Value 
                  0.18     
                  0.27     
                  0.14     
                  0.66     
                  0.86     
                  0.13     
                  0.82     
                  0.95     
                  0.13     
               
               
                 Lower limit of 95% CI 
                  0.755    
                  0.662    
                  0.798    
                  0.509    
                  0.415    
                  0.808    
                  0.452    
                  0.352    
                  0.813    
               
               
                 Upper limit of 95% CI 
                  4.50     
                  4.30     
                  5.14     
                  2.92     
                  2.87     
                  5.07     
                  2.73     
                  2.66     
                  5.21     
               
               
                 OR Quartile 4 
                  2.40     
                  2.30     
                  1.70     
                  1.91     
                  1.01     
                  2.57     
                  2.11     
                  0.938    
                  2.26     
               
               
                 p Value 
                  0.13     
                  0.11     
                  0.34     
                  0.20     
                  0.98     
                  0.076    
                  0.15     
                  0.91     
                  0.12     
               
               
                 Lower limit of 95% CI 
                  0.782    
                  0.826    
                  0.570    
                  0.705    
                  0.337    
                  0.905    
                  0.766    
                  0.293    
                  0.803    
               
               
                 Upper limit of 95% CI 
                  7.37     
                  6.40     
                  5.05     
                  5.19     
                  3.04     
                  7.30     
                  5.79     
                  3.00     
                  6.37     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  7.72 
                 10.6  
                  8.56  
                 10.5  
                  8.56 
                 10.5  
               
               
                 Average 
                 10.1  
                 13.2  
                 11.0   
                 13.6  
                 11.1  
                 13.8  
               
               
                 Stdev 
                  7.51 
                  9.17 
                  7.00  
                 10.5  
                  7.02 
                 10.9  
               
               
                 p (t-test) 
                   
                  0.12 
                   
                  0.18 
                   
                  0.16  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62  
                  1.32 
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8   
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 31   
                 53   
                 49    
                 35   
                 53   
                 31    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                   
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.41 
                 12.1  
                  9.00  
                 10.6  
                  9.37 
                 10.5  
               
               
                 Average 
                 11.5  
                 13.3  
                 12.2   
                 11.9  
                 12.2  
                 11.8  
               
               
                 Stdev 
                  8.82 
                  8.73 
                  8.88  
                  8.69 
                  8.84 
                  8.77  
               
               
                 p (t-test) 
                   
                  0.40 
                   
                  0.90 
                   
                  0.84  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62  
                  1.32 
                  1.62 
                  1.32  
               
               
                 Max 
                 38.9  
                 37.2  
                 38.9   
                 37.2  
                 38.9  
                 37.2  
               
               
                 n (Patient) 
                 53   
                 28   
                 57    
                 24   
                 60   
                 21    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.17 
                 10.6  
                  8.56  
                 11.4  
                  8.56 
                 11.4  
               
               
                 Average 
                 10.6  
                 13.2  
                 10.6   
                 14.1  
                 10.7  
                 14.2  
               
               
                 Stdev 
                  6.96 
                  9.33 
                  6.65  
                 10.2  
                  6.56 
                 10.5  
               
               
                 p (t-test) 
                   
                  0.19 
                   
                  0.078 
                   
                  0.073 
               
               
                 Min 
                  2.64 
                  1.32 
                  1.62  
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8   
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 30   
                 47   
                 43    
                 34    
                 45   
                 32    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.62     
                  0.58     
                  0.58     
                  0.55     
                  0.51     
                  0.59     
                  0.55     
                  0.50     
                  0.58     
               
               
                 SE 
                  0.062    
                  0.068    
                  0.066    
                  0.064    
                  0.071    
                  0.066    
                  0.066    
                  0.074    
                  0.067    
               
               
                 p Value 
                  0.055    
                  0.23     
                  0.21     
                  0.42     
                  0.93     
                  0.19     
                  0.43     
                  0.98     
                  0.22     
               
               
                 nCohort Non-persistent 
                 31       
                 53       
                 30       
                 49       
                 57       
                 43       
                 53       
                 60       
                 45       
               
               
                 nCohort Persistent 
                 53       
                 28       
                 47       
                 35       
                 24       
                 34       
                 31       
                 21       
                 32       
               
               
                 Cutoff Quartile 2 
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
               
               
                 Sensitivity 
                 79%    
                 79%    
                 79%    
                 77%    
                 75%    
                 79%    
                 77%    
                 76%    
                 78%    
               
               
                 Specificity 
                 32%    
                 26%    
                 30%    
                 27%    
                 25%    
                 28%    
                 26%    
                 25%    
                 27%    
               
               
                 Cutoff Quartile 3 
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
               
               
                 Sensitivity 
                 57%    
                 61%    
                 57%    
                 54%    
                 54%    
                 62%    
                 55%    
                 52%    
                 62%    
               
               
                 Specificity 
                 61%    
                 55%    
                 60%    
                 53%    
                 51%    
                 58%    
                 53%    
                 50%    
                 58%    
               
               
                 Cutoff Quartile 4 
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
               
               
                 Sensitivity 
                 30%    
                 39%    
                 30%    
                 31%    
                 29%    
                 35%    
                 32%    
                 29%    
                 34%    
               
               
                 Specificity 
                 84%    
                 81%    
                 80%    
                 80%    
                 75%    
                 81%    
                 79%    
                 75%    
                 80%    
               
               
                 OR Quartile 2 
                  1.82     
                  1.32     
                  1.59     
                  1.22     
                  0.977    
                  1.49     
                  1.23     
                  1.07     
                  1.30     
               
               
                 p Value 
                  0.24     
                  0.62     
                  0.39     
                  0.70     
                  0.97     
                  0.46     
                  0.70     
                  0.91     
                  0.63     
               
               
                 Lower limit of 95% CI 
                  0.666    
                  0.443    
                  0.556    
                  0.443    
                  0.324    
                  0.514    
                  0.435    
                  0.334    
                  0.447    
               
               
                 Upper limit of 95% CI 
                  4.96     
                  3.91     
                  4.52     
                  3.35     
                  2.94     
                  4.33     
                  3.48     
                  3.41     
                  3.78     
               
               
                 OR Quartile 3 
                  2.07     
                  1.87     
                  2.02     
                  1.34     
                  1.22     
                  2.24     
                  1.36     
                  1.10     
                  2.28     
               
               
                 p Value 
                  0.12     
                  0.19     
                  0.14     
                  0.51     
                  0.68     
                  0.085    
                  0.50     
                  0.85     
                  0.082    
               
               
                 Lower limit of 95% CI 
                  0.836    
                  0.736    
                  0.798    
                  0.562    
                  0.470    
                  0.895    
                  0.559    
                  0.407    
                  0.901    
               
               
                 Upper limit of 95% CI 
                  5.10     
                  4.74     
                  5.14     
                  3.20     
                  3.18     
                  5.63     
                  3.31     
                  2.97     
                  5.77     
               
               
                 OR Quartile 4 
                  2.25     
                  2.78     
                  1.70     
                  1.79     
                  1.26     
                  2.39     
                  1.82     
                  1.20     
                  2.10     
               
               
                 p Value 
                  0.16     
                  0.050    
                  0.34     
                  0.25     
                  0.67     
                  0.10     
                  0.24     
                  0.75     
                  0.16     
               
               
                 Lower limit of 95% CI 
                  0.732    
                  0.999    
                  0.570    
                  0.660    
                  0.435    
                  0.842    
                  0.666    
                  0.394    
                  0.746    
               
               
                 Upper limit of 95% CI 
                  6.91     
                  7.75     
                  5.05     
                  4.84     
                  3.68     
                  6.76     
                  4.96     
                  3.65     
                  5.88     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  7.83 
                 10.5  
                  8.56 
                 10.5  
                  8.78 
                 10.2   
               
               
                 Average 
                 10.3  
                 13.1  
                 11.1  
                 13.3  
                 11.0  
                 13.6   
               
               
                 Stdev 
                  7.60 
                  9.14 
                  7.11 
                 10.3  
                  6.99 
                 10.6   
               
               
                 p (t-test) 
                   
                  0.16 
                   
                  0.25  
                   
                  0.18  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8  
                 38.9  
                 30.8  
                 38.9   
               
               
                 n (Patient) 
                 30   
                 54   
                 47   
                 37    
                 50   
                 34    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.41  
                 12.1  
                  9.00 
                 10.6  
                  9.00 
                 10.6   
               
               
                 Average 
                 11.1  
                 13.9  
                 11.8  
                 12.7  
                 11.7  
                 13.1   
               
               
                 Stdev 
                  8.06  
                  9.76 
                  8.23 
                  9.97  
                  8.17 
                 10.2   
               
               
                 p (t-test) 
                   
                  0.17 
                   
                  0.67  
                   
                  0.52  
               
               
                 Min 
                  1.62  
                  1.32 
                  1.62 
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 36.8  
                 38.9  
                 36.8  
                 38.9  
                 36.8  
                 38.9   
               
               
                 n (Patient) 
                 51    
                 30   
                 55   
                 26    
                 57   
                 24    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.41  
                 10.5  
                  8.48  
                 10.8  
                  8.56 
                 11.4  
               
               
                 Average 
                 10.7  
                 13.0  
                 10.5  
                 14.0  
                 10.5  
                 14.1  
               
               
                 Stdev 
                  7.03  
                  9.29  
                  6.59  
                 10.0  
                  6.51 
                 10.1  
               
               
                 p (t-test) 
                   
                  0.25  
                   
                  0.069 
                   
                  0.063 
               
               
                 Min 
                  2.64  
                  1.32  
                  1.62  
                  1.32  
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8  
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 29    
                 48    
                 40    
                 37    
                 41   
                 36    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.60     
                  0.59     
                  0.57     
                  0.54     
                  0.52     
                  0.59     
                  0.55     
                  0.53     
                  0.59     
               
               
                 SE 
                  0.063    
                  0.067    
                  0.067    
                  0.064    
                  0.069    
                  0.065    
                  0.065    
                  0.071    
                  0.065    
               
               
                 p Value 
                  0.096    
                  0.18     
                  0.32     
                  0.51     
                  0.81     
                  0.15     
                  0.46     
                  0.66     
                  0.18     
               
               
                 nCohort Non-persistent 
                 30       
                 51       
                 29       
                 47       
                 55       
                 40       
                 50       
                 57       
                 41       
               
               
                 nCohort Persistent 
                 54       
                 30       
                 48       
                 37       
                 26       
                 37       
                 34       
                 24       
                 36       
               
               
                 Cutoff Quartile 2 
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
               
               
                 Sensitivity 
                 78%    
                 77%    
                 77%    
                 76%    
                 73%    
                 78%    
                 76%    
                 75%    
                 78%    
               
               
                 Specificity 
                 30%    
                 25%    
                 28%    
                 26%    
                 24%    
                 28%    
                 26%    
                 25%    
                 27%    
               
               
                 Cutoff Quartile 3 
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
               
               
                 Sensitivity 
                 56%    
                 60%    
                 56%    
                 54%    
                 54%    
                 62%    
                 53%    
                 54%    
                 61%    
               
               
                 Specificity 
                 60%    
                 55%    
                 59%    
                 53%    
                 51%    
                 60%    
                 52%    
                 51%    
                 59%    
               
               
                 Cutoff Quartile 4 
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
               
               
                 Sensitivity 
                 30%    
                 40%    
                 29%    
                 30%    
                 31%    
                 35%    
                 32%    
                 33%    
                 36%    
               
               
                 Specificity 
                 83%    
                 82%    
                 79%    
                 79%    
                 76%    
                 82%    
                 80%    
                 77%    
                 83%    
               
               
                 OR Quartile 2 
                  1.50     
                  1.12     
                  1.28     
                  1.07     
                  0.840    
                  1.38     
                  1.14     
                  0.977    
                  1.28     
               
               
                 p Value 
                  0.43     
                  0.83     
                  0.65     
                  0.90     
                  0.75     
                  0.55     
                  0.80     
                  0.97     
                  0.64     
               
               
                 Lower limit of 95% CI 
                  0.546    
                  0.391    
                  0.445    
                  0.394    
                  0.289    
                  0.483    
                  0.414    
                  0.324    
                  0.451    
               
               
                 Upper limit of 95% CI 
                  4.12     
                  3.23     
                  3.69     
                  2.89     
                  2.44     
                  3.91     
                  3.15     
                  2.94     
                  3.65     
               
               
                 OR Quartile 3 
                  1.88     
                  1.83     
                  1.82     
                  1.34     
                  1.21     
                  2.46     
                  1.22     
                  1.22     
                  2.22     
               
               
                 p Value 
                  0.17     
                  0.20     
                  0.21     
                  0.51     
                  0.69     
                  0.054    
                  0.66     
                  0.68     
                  0.087    
               
               
                 Lower limit of 95% CI 
                  0.757    
                  0.731    
                  0.716    
                  0.564    
                  0.475    
                  0.985    
                  0.509    
                  0.470    
                  0.890    
               
               
                 Upper limit of 95% CI 
                  4.64     
                  4.56     
                  4.63     
                  3.17     
                  3.08     
                  6.17     
                  2.92     
                  3.18     
                  5.53     
               
               
                 OR Quartile 4 
                  2.11     
                  3.11     
                  1.58     
                  1.57     
                  1.44     
                  2.55     
                  1.91     
                  1.69     
                  2.75     
               
               
                 p Value 
                  0.19     
                  0.030    
                  0.41     
                  0.38     
                  0.50     
                  0.083    
                  0.20     
                  0.33     
                  0.062    
               
               
                 Lower limit of 95% CI 
                  0.684    
                  1.12     
                  0.529    
                  0.580    
                  0.508    
                  0.886    
                  0.705    
                  0.592    
                  0.951    
               
               
                 Upper limit of 95% CI 
                  6.48     
                  8.68     
                  4.71     
                  4.22     
                  4.06     
                  7.36     
                  5.19     
                  4.84     
                  7.93     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  7.83 
                 10.5  
                  8.41 
                 10.5  
                  8.48 
                 10.2  
               
               
                 Average 
                 10.3  
                 13.0  
                 11.1  
                 13.2  
                 11.0  
                 13.5  
               
               
                 Stdev 
                  7.83 
                  9.00 
                  7.25 
                 10.1  
                  7.12 
                 10.3  
               
               
                 p (t-test) 
                   
                  0.18 
                   
                  0.27 
                   
                  0.19  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8  
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 28   
                 56   
                 45   
                 39   
                 48   
                 36    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 8.41 
                 12.1  
                  9.00 
                 10.6  
                  9.00 
                 10.6  
               
               
                 Average 
                 11.1  
                 13.9  
                 11.8  
                 12.7  
                 11.7  
                 13.1  
               
               
                 Stdev 
                  8.06 
                  9.76 
                  8.23 
                  9.97 
                  8.17 
                 10.2  
               
               
                 p (t-test) 
                   
                  0.17 
                   
                  0.67 
                   
                  0.52  
               
               
                 Min 
                  1.62 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32  
               
               
                 Max 
                 36.8  
                 38.9  
                 36.8  
                 38.9  
                 36.8  
                 38.9  
               
               
                 n (Patient) 
                 51   
                 30   
                 55   
                 26   
                 57   
                 24    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent 
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  8.48 
                 10.4  
                  8.48 
                 10.7  
                  8.48 
                 10.7  
               
               
                 Average 
                 10.8  
                 12.9  
                 10.6  
                 13.7  
                 10.5  
                 13.9  
               
               
                 Stdev 
                  7.12 
                  9.23 
                  6.74 
                  9.82 
                  6.58 
                 10.0  
               
               
                 p (t-test) 
                   
                  0.31 
                   
                  0.11 
                   
                  0.077 
               
               
                 Min 
                  2.64 
                  1.32 
                  1.62 
                  1.32 
                  1.62 
                  1.32  
               
               
                 Max 
                 30.8  
                 38.9  
                 30.8  
                 38.9  
                 30.8  
                 38.9  
               
               
                 n (Patient) 
                 28   
                 49   
                 38   
                 39   
                 40   
                 37    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.61     
                  0.59     
                  0.56     
                  0.55     
                  0.52     
                  0.58     
                  0.55     
                  0.53     
                  0.59     
               
               
                 SE 
                  0.064    
                  0.067    
                  0.068    
                  0.063    
                  0.069    
                  0.065    
                  0.064    
                  0.071    
                  0.065    
               
               
                 p Value 
                  0.083    
                  0.18     
                  0.39     
                  0.43     
                  0.81     
                  0.20     
                  0.39     
                  0.66     
                  0.19     
               
               
                 nCohort Non-persistent 
                 28      
                 51      
                 28      
                 45      
                 55      
                 38      
                 48      
                 57      
                 40      
               
               
                 nCohort Persistent 
                 56      
                 30      
                 49      
                 39      
                 26      
                 39      
                 36      
                 24      
                 37      
               
               
                 Cutoff Quartile 2 
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
                  6.19     
                  6.19     
                  6.24     
               
               
                 Sensitivity 
                 79%    
                 77%    
                 78%    
                 77%    
                 73%    
                 79%    
                 78%    
                 75%    
                 78%    
               
               
                 Specificity 
                 32%    
                 25%    
                 29%    
                 27%    
                 24%    
                 29%    
                 27%    
                 25%    
                 28%    
               
               
                 Cutoff Quartile 3 
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
                  9.66     
                  9.75     
                  9.75     
               
               
                 Sensitivity 
                 55%    
                 60%    
                 55%    
                 54%    
                 54%    
                 59%    
                 53%    
                 54%    
                 59%    
               
               
                 Specificity 
                 61%    
                 55%    
                 57%    
                 53%    
                 51%    
                 58%    
                 52%    
                 51%    
                 57%    
               
               
                 Cutoff Quartile 4 
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
                 16.0     
                 15.9     
                 15.9     
               
               
                 Sensitivity 
                 29%    
                 40%    
                 29%    
                 28%    
                 31%    
                 33%    
                 31%    
                 33%    
                 35%    
               
               
                 Specificity 
                 82%    
                 82%    
                 79%    
                 78%    
                 76%    
                 82%    
                 79%    
                 77%    
                 82%    
               
               
                 OR Quartile 2 
                  1.74     
                  1.12     
                  1.38     
                  1.21     
                  0.840    
                  1.58     
                  1.30     
                  0.977    
                  1.38     
               
               
                 p Value 
                  0.29     
                  0.83     
                  0.55     
                  0.70     
                  0.75     
                  0.39     
                  0.61     
                  0.97     
                  0.55     
               
               
                 Lower limit of 95% CI 
                  0.628    
                  0.391    
                  0.479    
                  0.448    
                  0.289    
                  0.554    
                  0.473    
                  0.324    
                  0.483    
               
               
                 Upper limit of 95% CI 
                  4.81     
                  3.23     
                  3.99     
                  3.28     
                  2.44     
                  4.50     
                  3.57     
                  2.94     
                  3.91     
               
               
                 OR Quartile 3 
                  1.92     
                  1.83     
                  1.64     
                  1.33     
                  1.21     
                  1.98     
                  1.21     
                  1.22     
                  1.98     
               
               
                 p Value 
                  0.17     
                  0.20     
                  0.30     
                  0.51     
                  0.69     
                  0.14     
                  0.66     
                  0.68     
                  0.14     
               
               
                 Lower limit of 95% CI 
                  0.761    
                  0.731    
                  0.641    
                  0.564    
                  0.475    
                  0.798    
                  0.511    
                  0.470    
                  0.801    
               
               
                 Upper limit of 95% CI 
                  4.83     
                  4.56     
                  4.17     
                  3.15     
                  3.08     
                  4.89     
                  2.89     
                  3.18     
                  4.92     
               
               
                 OR Quartile 4 
                  1.84     
                  3.11     
                  1.47     
                  1.38     
                  1.44     
                  2.21     
                  1.67     
                  1.69     
                  2.55     
               
               
                 p Value 
                  0.29     
                  0.030    
                  0.49     
                  0.53     
                  0.50     
                  0.14     
                  0.31     
                  0.33     
                  0.083    
               
               
                 Lower limit of 95% CI 
                  0.596    
                  1.12     
                  0.491    
                  0.511    
                  0.508    
                  0.770    
                  0.619    
                  0.592    
                  0.886    
               
               
                 Upper limit of 95% CI 
                  5.68     
                  8.68     
                  4.38     
                  3.70     
                  4.06     
                  6.37     
                  4.52     
                  4.84     
                  7.36     
               
               
                   
               
            
           
         
       
     
     Example 16. Use of Tyrosine-Protein Kinase Receptor UFO for Evaluating Renal Status in Patients Admitted to the ICU: Persistent at RIFLE F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Tyrosine-protein kinase receptor UFO is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output. Two cohorts are defined to represent a “persistent” and a “non-persistent” population. “Persistent” indicates those patients whose minimum RIFLE stage during a period of 24, 48 or 72 hours is failure (F) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. “Non-persistent” indicates those patients who are not persistent at failure (F) and whose minimum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0), risk of injury (R), or injury (I) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. If a patient dies after failure (F) or is placed on renal replacement therapy (RRT) at any time from sample collection to 24, 48, 72, 96 or 168 hours after sample collection, the patient is considered “persistent”. 
     The ability to distinguish the “persistent” and “non-persistent” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 16.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.87  
                  1.89  
                  4.87  
                  1.22  
                  4.85  
                  1.16  
               
               
                 Average 
                  5.74  
                  2.51  
                  5.59  
                  1.43  
                  5.54  
                  1.35  
               
               
                 Stdev 
                  4.27  
                  2.28  
                  4.12  
                  1.09  
                  4.10  
                  1.09  
               
               
                 p (t-test) 
                   
                  0.0011 
                   
                 3.5E−4 
                   
                 4.8E−4 
               
               
                 Min 
                  0.432 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276 
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  4.01  
                 20.6  
                  4.01  
               
               
                 n (Patient) 
                 61    
                 22    
                 69    
                 14    
                 70    
                 13    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.83  
                  1.52  
                  4.60  
                  1.45  
                  4.45  
                  1.45  
               
               
                 Average 
                  5.45  
                  2.17  
                  5.30  
                  2.25  
                  5.20  
                  2.35  
               
               
                 Stdev 
                  4.22  
                  2.35  
                  4.20  
                  2.57  
                  4.18  
                  2.85  
               
               
                 p (t-test) 
                   
                  0.0062 
                   
                  0.022  
                   
                  0.051  
               
               
                 Min 
                  0.432 
                   
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.11  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 66    
                 14    
                 69    
                 11    
                 71    
                  9    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.87  
                  2.78  
                  4.87  
                  1.29  
                  4.87  
                  1.29  
               
               
                 Average 
                  5.64  
                  2.97  
                  5.51  
                  1.60  
                  5.51  
                  1.60  
               
               
                 Stdev 
                  4.36  
                  2.35  
                  4.19  
                  1.13  
                  4.19  
                  1.13  
               
               
                 p (t-test) 
                   
                  0.018 
                   
                  0.0071 
                   
                  0.0071 
               
               
                 Min 
                  0.366 
                  0.489 
                  0.366 
                  0.489  
                  0.366 
                  0.489  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  4.01  
                 20.6  
                  4.01  
               
               
                 n (Patient) 
                 61    
                 17    
                 69    
                  9    
                 69    
                  9    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.22     
                  0.20     
                  0.29     
                  0.12      
                  0.22     
                  0.16      
                  0.11      
                  0.23     
                  0.16      
               
               
                 SE 
                  0.063     
                  0.075     
                  0.077     
                  0.061     
                  0.086     
                  0.085      
                  0.062     
                  0.096     
                  0.085     
               
               
                 p Value 
                 1.4E−5 
                 7.6E−5 
                  0.0067    
                 5.3E−10 
                  0.0013    
                 7.5E−5 
                 3.0E−10 
                  0.0058    
                 7.5E−5 
               
               
                 nCohort  
                 61       
                 66       
                 61       
                 69        
                 69       
                 69        
                 70        
                 71       
                 69        
               
               
                 Non-persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 22       
                 14       
                 17       
                 14        
                 11       
                  9        
                 13        
                  9       
                  9        
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                  2.05     
                  1.90     
                  2.02     
                  2.05      
                  1.90     
                  2.02      
                  2.05      
                  1.90     
                  2.02      
               
               
                 Sensitivity 
                 50%    
                 43%    
                 53%    
                 29%     
                 45%    
                 22%     
                 23%     
                 44%    
                 22%     
               
               
                 Specificity 
                 16%    
                 18%    
                 20%    
                 16%     
                 20%    
                 19%     
                 16%     
                 21%    
                 19%     
               
               
                 Cutoff Quartile 3 
                  4.01     
                  3.91     
                  4.44     
                  4.01      
                  3.91     
                  4.44      
                  4.01      
                  3.91     
                  4.44      
               
               
                 Sensitivity 
                 23%    
                 14%    
                 18%    
                  7%     
                 18%    
                  0%     
                  8%     
                 22%    
                  0%     
               
               
                 Specificity 
                 39%    
                 42%    
                 41%    
                 41%     
                 45%    
                 43%     
                 41%     
                 46%    
                 43%     
               
               
                 Cutoff Quartile 4 
                  6.30     
                  6.30     
                  6.36     
                  6.30      
                  6.30     
                  6.36      
                  6.30      
                  6.30     
                  6.36      
               
               
                 Sensitivity 
                  5%    
                  7%    
                  6%    
                  0%     
                  9%    
                  0%     
                  0%     
                 11%    
                  0%     
               
               
                 Specificity 
                 67%    
                 71%    
                 69%    
                 70%     
                 72%    
                 71%     
                 70%     
                 73%    
                 71%     
               
               
                 OR Quartile 2 
                  0.196     
                  0.167     
                  0.276     
                  0.0759     
                  0.212     
                  0.0663     
                  0.0559     
                  0.214     
                  0.0663     
               
               
                 p Value 
                  0.0030    
                  0.0043    
                  0.027     
                 1.4E−4 
                  0.022     
                  0.0016     
                 8.9E−5 
                  0.035     
                  0.0016     
               
               
                 Lower limit  
                  0.0668    
                  0.0487    
                  0.0879    
                  0.0201     
                  0.0564    
                  0.0123     
                  0.0132     
                  0.0511    
                  0.0123     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  0.575     
                  0.570     
                  0.864     
                  0.286     
                  0.797     
                  0.357     
                  0.237     
                  0.898     
                  0.357     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                  0.191     
                  0.123     
                  0.149     
                  0.0525     
                  0.181     
                  0.0406     
                  0.0589     
                  0.248     
                  0.0406     
               
               
                 p Value 
                  0.0038    
                  0.0090    
                  0.0056    
                  0.0057     
                  0.037     
                  0.029     
                  0.0081     
                  0.096     
                  0.029     
               
               
                 Lower limit  
                  0.0621    
                  0.0254    
                  0.0387    
                  0.00650    
                  0.0365    
                  0.00227    
                  0.00726    
                  0.0482    
                  0.00227    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  0.586     
                  0.593     
                  0.572     
                  0.425     
                  0.901     
                  0.726     
                  0.479     
                  1.28     
                  0.726     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                  0.0976    
                  0.190     
                  0.138     
                  0.0778     
                  0.263     
                  0.127     
                  0.0853     
                  0.342     
                  0.127     
               
               
                 p Value 
                  0.028     
                  0.12     
                  0.064     
                  0.081     
                  0.22     
                  0.16      
                  0.092     
                  0.33     
                  0.16      
               
               
                 Lower limit  
                  0.0122    
                  0.0232    
                  0.0171    
                  0.00443    
                  0.0315    
                  0.00706    
                  0.00485    
                  0.0401    
                  0.00706    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  0.778     
                  1.56     
                  1.12     
                  1.36      
                  2.20     
                  2.29      
                  1.50      
                  2.92     
                  2.29      
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                   
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.88  
                  2.19  
                  4.87  
                  1.29  
                  4.87  
                  1.22  
               
               
                 Average 
                  5.79  
                  2.79  
                  5.62  
                  2.02  
                  5.58  
                  2.00  
               
               
                 Stdev 
                  4.29  
                  2.58  
                  4.14  
                  2.25  
                  4.12  
                  2.32  
               
               
                 p (t-test) 
                   
                  0.0017 
                   
                 8.9E−4 
                   
                  0.0013 
               
               
                 Min 
                  0.502 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 58    
                 25    
                 66 
                 17    
                 67    
                 16    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.83  
                  1.52  
                  4.60  
                  1.45  
                  4.45  
                  1.45  
               
               
                 Average 
                  5.45  
                  2.17  
                  5.30  
                  2.25  
                  5.20  
                  2.35  
               
               
                 Stdev 
                  4.22  
                  2.35  
                  4.20  
                  2.57  
                  4.18  
                  2.85  
               
               
                 p (t-test) 
                   
                  0.0062 
                   
                  0.022  
                   
                  0.051  
               
               
                 Min 
                  0.432 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.11  
                 20.6  
                  9.11  
                 20.6   
                  9.11  
               
               
                 n (Patient) 
                 66    
                 14    
                 69 
                 11    
                 71    
                  9    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.88  
                  2.78  
                  4.87  
                  1.29  
                  4.87  
                  1.29  
               
               
                 Average 
                  5.77  
                  3.10  
                  5.62  
                  2.25  
                  5.62  
                  2.25  
               
               
                 Stdev 
                  4.38  
                  2.67  
                  4.20  
                  2.49  
                  4.20  
                  2.49  
               
               
                 p (t-test) 
                   
                  0.011  
                   
                  0.0067 
                   
                  0.0067 
               
               
                 Min 
                  0.366 
                  0.398  
                  0.366 
                  0.398  
                  0.366 
                  0.398  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 57    
                 21    
                 65    
                 13    
                 65    
                 13    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.24     
                  0.20     
                  0.28     
                  0.17     
                  0.22     
                  0.20     
                  0.17     
                  0.23     
                  0.20     
               
               
                 SE 
                  0.062     
                  0.075     
                  0.070     
                  0.065     
                  0.086     
                  0.077     
                  0.066     
                  0.096     
                  0.077     
               
               
                 p Value 
                 3.7E−5 
                 7.6E−5 
                  0.0021    
                 3.7E−7 
                  0.0013    
                 1.2E−4 
                 5.6E−7 
                  0.0058    
                 1.2E−4 
               
               
                 nCohort Non-persistent 
                 58       
                 66       
                 57       
                 66       
                 69       
                 65       
                 67       
                 71       
                 65       
               
               
                 nCohort Persistent 
                 25       
                 14       
                 21       
                 17       
                 11       
                 13       
                 16       
                  9       
                 13       
               
               
                 Cutoff Quartile 2 
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
               
               
                 Sensitivity 
                 52%    
                 43%    
                 52%    
                 35%    
                 45%    
                 31%    
                 31%    
                 44%    
                 31%    
               
               
                 Specificity 
                 16%    
                 18%    
                 18%    
                 15%    
                 20%    
                 17%    
                 15%    
                 21%    
                 17%    
               
               
                 Cutoff Quartile 3 
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
               
               
                 Sensitivity 
                 28%    
                 14%    
                 24%    
                 18%    
                 18%    
                 15%    
                 19%    
                 22%    
                 15%    
               
               
                 Specificity 
                 40%    
                 42%    
                 40%    
                 41%    
                 45%    
                 43%    
                 42%    
                 46%    
                 43%    
               
               
                 Cutoff Quartile 4 
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30     
                  6.36     
               
               
                 Sensitivity 
                  8%      
                  7%    
                 10%    
                  6%    
                  9%    
                  8%    
                  6%    
                 11%    
                  8%    
               
               
                 Specificity 
                 67%    
                 71%    
                 68%    
                 70%    
                 72%    
                 71%    
                 70%    
                 73%    
                 71%    
               
               
                 OR Quartile 2 
                  0.199     
                  0.167     
                  0.234     
                  0.0974 
                  0.212     
                  0.0905    
                  0.0797    
                  0.214     
                  0.0905    
               
               
                 p Value 
                  0.0028    
                  0.0043    
                  0.0093    
                 1.4E−4 
                  0.022     
                 4.6E−4 
                 7.6E−5 
                  0.035     
                 4.6E−4 
               
               
                 Lower limit of 95% CI 
                  0.0690    
                  0.0487    
                  0.0783    
                  0.0293    
                  0.0564    
                  0.0236    
                  0.0228    
                  0.0511    
                  0.0236    
               
               
                 Upper limit of 95% CI 
                  0.574     
                  0.570     
                  0.700     
                  0.324     
                  0.797     
                  0.347     
                  0.279     
                  0.898     
                  0.347     
               
               
                 OR Quartile 3 
                  0.256     
                  0.123     
                  0.211     
                  0.148     
                  0.181     
                  0.138     
                  0.166     
                  0.248     
                  0.138     
               
               
                 p Value 
                  0.0087    
                  0.0090    
                  0.0073    
                  0.0053    
                  0.037     
                  0.014     
                  0.0089    
                  0.096     
                  0.014     
               
               
                 Lower limit of 95% CI 
                  0.0922    
                  0.0254    
                  0.0679    
                  0.0388    
                  0.0365    
                  0.0282    
                  0.0431    
                  0.0482    
                  0.0282    
               
               
                 Upper limit of 95% CI 
                  0.708     
                  0.593     
                  0.658     
                  0.567     
                  0.901     
                  0.671     
                  0.637     
                  1.28     
                  0.671     
               
               
                 OR Quartile 4 
                  0.178     
                  0.190     
                  0.228     
                  0.144     
                  0.263     
                  0.202     
                  0.157     
                  0.342     
                  0.202     
               
               
                 p Value 
                  0.029     
                  0.12     
                  0.063     
                  0.069     
                  0.22     
                  0.14     
                  0.082     
                  0.33     
                  0.14     
               
               
                 Lower limit of 95% CI 
                  0.0381    
                  0.0232    
                  0.0479    
                  0.0178    
                  0.0315    
                  0.0245    
                  0.0194    
                  0.0401    
                  0.0245    
               
               
                 Upper limit of 95% CI 
                  0.837     
                  1.56     
                  1.09     
                  1.16     
                  2.20     
                  1.66     
                  1.27     
                  2.92     
                  1.66     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.88  
                  2.32  
                  4.87  
                  1.37  
                  4.87  
                  1.29  
               
               
                 Average 
                  5.83  
                  2.81  
                  5.66  
                  2.08  
                  5.61  
                  2.06  
               
               
                 Stdev 
                  4.32  
                  2.53  
                  4.16  
                  2.20  
                  4.14  
                  2.26  
               
               
                 p (t-test) 
                   
                  0.0014 
                   
                 7.2E−4 
                   
                  0.0010 
               
               
                 Min 
                  0.502 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 57    
                 26    
                 65    
                 18    
                 66    
                 17    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.84  
                  1.59  
                  4.60  
                  1.45  
                  4.45  
                  1.45  
               
               
                 Average 
                  5.49  
                  2.24  
                  5.30  
                  2.25  
                  5.20  
                  2.35  
               
               
                 Stdev 
                  4.24  
                  2.29  
                  4.20  
                  2.57  
                  4.18  
                  2.85  
               
               
                 p (t-test) 
                   
                  0.0055 
                   
                  0.022  
                   
                  0.051  
               
               
                 Min 
                  0.432 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.11  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 65    
                 15    
                 69    
                 11    
                 71    
                  9    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.02  
                  2.91  
                  4.88  
                  1.59  
                  4.88  
                  1.44  
               
               
                 Average 
                  5.82  
                  3.11  
                  5.70  
                  2.37  
                  5.66  
                  2.30  
               
               
                 Stdev 
                  4.41  
                  2.60  
                  4.24  
                  2.33  
                  4.22  
                  2.40  
               
               
                 p (t-test) 
                   
                  0.0087 
                   
                  0.0045 
                   
                  0.0054 
               
               
                 Min 
                  0.366 
                  0.398  
                  0.366 
                  0.398  
                  0.366 
                  0.398  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 56    
                 22    
                 63    
                 15    
                 64    
                 14    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                   
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.24     
                  0.21     
                  0.28     
                  0.18     
                  0.22     
                  0.21     
                  0.18     
                  0.23     
                  0.21     
               
               
                 SE 
                  0.061     
                  0.074     
                  0.069     
                  0.064     
                  0.086     
                  0.074     
                  0.065     
                  0.096     
                  0.076     
               
               
                 p Value 
                 2.9E−5 
                 8.7E−5 
                  0.0016    
                 4.2E−7 
                  0.0013    
                 1.0E−4 
                 6.8E−7 
                  0.0058    
                 1.1E−4 
               
               
                 nCohort Non-persistent 
                 57       
                 65       
                 56       
                 65       
                 69       
                 63       
                 66       
                 71       
                 64       
               
               
                 nCohort Persistent 
                 26       
                 15       
                 22       
                 18       
                 11       
                 15       
                 17       
                  9       
                 14       
               
               
                 Cutoff Quartile 2 
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
               
               
                 Sensitivity 
                 54%    
                 47%    
                 55%    
                 39%    
                 45%    
                 40%    
                 35%    
                 44%    
                 36%    
               
               
                 Specificity 
                 16%    
                 18%    
                 18%    
                 15%    
                 20%    
                 17%    
                 15%    
                 21%    
                 17%    
               
               
                 Cutoff Quartile 3 
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
               
               
                 Sensitivity 
                 27%    
                 13%    
                 23%    
                 17%    
                 18%    
                 13%    
                 18%    
                 22%    
                 14%    
               
               
                 Specificity 
                 39%    
                 42%    
                 39%    
                 40%    
                 45%    
                 41%    
                 41%    
                 46%    
                 42%    
               
               
                 Cutoff Quartile 4 
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30     
                  6.36     
               
               
                 Sensitivity 
                  8%    
                  7%    
                  9%    
                  6%    
                  9%    
                  7%    
                  6%    
                 11%    
                  7%    
               
               
                 Specificity 
                 67%    
                 71%    
                 68%    
                 69%    
                 72%    
                 70%    
                 70%    
                 73%    
                 70%    
               
               
                 OR Quartile 2 
                  0.219     
                  0.198     
                  0.261     
                  0.116     
                  0.212     
                  0.141     
                  0.0974    
                  0.214     
                  0.115     
               
               
                 p Value 
                  0.0045    
                  0.0078    
                  0.015     
                 2.8E−4 
                  0.022     
                  0.0017    
                 1.4E−4 
                  0.035     
                 8.7E−4 
               
               
                 Lower limit of 95% CI 
                  0.0766    
                  0.0601    
                  0.0884    
                  0.0362    
                  0.0564    
                  0.0416    
                  0.0293    
                  0.0511    
                  0.0323    
               
               
                 Upper limit of 95% CI 
                  0.625     
                  0.653     
                  0.770     
                  0.370     
                  0.797     
                  0.478     
                  0.324     
                  0.898     
                  0.411     
               
               
                 OR Quartile 3 
                  0.232     
                  0.109     
                  0.190     
                  0.133     
                  0.181     
                  0.108     
                  0.148     
                  0.248     
                  0.122     
               
               
                 p Value 
                  0.0048    
                  0.0057    
                  0.0041    
                  0.0031    
                  0.037     
                  0.0055    
                  0.0053    
                  0.096     
                  0.0088    
               
               
                 Lower limit of 95% CI 
                  0.0837    
                  0.0228    
                  0.0613    
                  0.0351    
                  0.0365    
                  0.0225    
                  0.0388    
                  0.0482    
                  0.0251    
               
               
                 Upper limit of 95% CI 
                  0.641     
                  0.525     
                  0.590     
                  0.507     
                  0.901     
                  0.520     
                  0.567     
                  1.28     
                  0.589     
               
               
                 OR Quartile 4 
                  0.167     
                  0.173     
                  0.211     
                  0.132     
                  0.263     
                  0.165     
                  0.144     
                  0.342     
                  0.182     
               
               
                 p Value 
                  0.023     
                  0.10     
                  0.050     
                  0.057     
                  0.22     
                  0.093     
                  0.069     
                  0.33     
                  0.11     
               
               
                 Lower limit of 95% CI 
                  0.0356    
                  0.0212    
                  0.0445    
                  0.0165    
                  0.0315    
                  0.0203    
                  0.0178    
                  0.0401    
                  0.0222    
               
               
                 Upper limit of 95% CI 
                  0.781     
                  1.41     
                  1.00     
                  1.06     
                  2.20     
                  1.35     
                  1.16     
                  2.92     
                  1.49     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 96 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.88  
                  2.32  
                  4.88  
                  1.45  
                  4.87  
                  1.37  
               
               
                 Average 
                  5.83  
                  2.81  
                  5.69  
                  2.16  
                  5.64  
                  2.15  
               
               
                 Stdev 
                  4.32  
                  2.53  
                  4.18  
                  2.17  
                  4.17  
                  2.23  
               
               
                 p (t-test) 
                   
                  0.0014 
                   
                 6.8E−4 
                   
                 9.9E−4 
               
               
                 Min 
                  0.502 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 57    
                 26    
                 64    
                 19    
                 65    
                 18    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.84  
                  1.59  
                  4.71  
                  1.82  
                  4.53 
                  1.82  
               
               
                 Average 
                  5.49  
                  2.24  
                  5.32  
                  2.36  
                  5.22 
                  2.48  
               
               
                 Stdev 
                  4.24  
                  2.29  
                  4.23  
                  2.49  
                  4.21 
                  2.72  
               
               
                 p (t-test) 
                   
                  0.0055 
                   
                  0.022  
                   
                  0.049  
               
               
                 Min 
                  0.432 
                  0.276  
                  0.366 
                  0.276  
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.11  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 65    
                 15    
                 68    
                 12    
                 70    
                 10    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.02  
                  2.91  
                  5.02  
                  1.59  
                  4.88  
                  1.59  
               
               
                 Average 
                  5.82  
                  3.11  
                  5.73  
                  2.45  
                  5.69  
                  2.39  
               
               
                 Stdev 
                  4.41  
                  2.60  
                  4.27  
                  2.27  
                  4.25  
                  2.34  
               
               
                 p (t-test) 
                   
                  0.0087 
                   
                  0.0041 
                   
                  0.0050 
               
               
                 Min 
                  0.366 
                  0.398  
                  0.366 
                  0.398  
                  0.366 
                  0.398  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 56    
                 22    
                 62    
                 16    
                 63    
                 15    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.24     
                  0.21     
                  0.28     
                  0.19     
                  0.24     
                  0.22     
                  0.19     
                  0.25     
                  0.22     
               
               
                 SE 
                  0.061     
                  0.074     
                  0.069     
                  0.063     
                  0.084     
                  0.073     
                  0.065     
                  0.093     
                  0.074     
               
               
                 p Value 
                 2.9E−5 
                 8.7E−5 
                  0.0016    
                 7.4E−7 
                  0.0019    
                 1.2E−4 
                 1.3E−6 
                  0.0081    
                 1.4E−4 
               
               
                 nCohort Non-persistent 
                 57       
                 65       
                 56       
                 64       
                 68       
                 62       
                 65       
                 70       
                 63       
               
               
                 nCohort Persistent 
                 26       
                 15       
                 22       
                 19       
                 12       
                 16       
                 18       
                 10       
                 15       
               
               
                 Cutoff Quartile 2 
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
               
               
                 Sensitivity 
                 54%    
                 47%    
                 55%    
                 42%    
                 50%    
                 44%    
                 39%    
                 50%    
                 40%    
               
               
                 Specificity 
                 16%    
                 18%    
                 18%    
                 16%    
                 21%    
                 18%    
                 15%    
                 21%    
                 17%    
               
               
                 Cutoff Quartile 3 
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
               
               
                 Sensitivity 
                 27%    
                 13%    
                 23%    
                 16%    
                 17%    
                 12%    
                 17%    
                 20%    
                 13%    
               
               
                 Specificity 
                 39%    
                 42%    
                 39%    
                 39%    
                 44%    
                 40%    
                 40%    
                 46%    
                 41%    
               
               
                 Cutoff Quartile 4 
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30      
                  6.36     
                  6.30     
                  6.30     
                  6.36     
               
               
                 Sensitivity 
                  8%    
                  7%    
                  9%    
                  5%    
                  8%    
                  6%    
                  6%    
                 10%    
                  7%    
               
               
                 Specificity 
                 67%    
                 71%    
                 68%    
                 69%    
                 72%    
                 69%    
                 69%    
                 73%    
                 70%    
               
               
                 OR Quartile 2 
                  0.219     
                  0.198     
                  0.261     
                  0.135     
                  0.259     
                  0.168     
                  0.116     
                  0.273     
                  0.141     
               
               
                 p Value 
                  0.0045    
                  0.0078    
                  0.015     
                  5.3E−4    
                  0.038     
                  0.0031    
                  2.8E−4 
                  0.062     
                  0.0017    
               
               
                 Lower limit of 95% CI 
                  0.0766    
                  0.0601    
                  0.0884    
                  0.0434    
                  0.0724    
                  0.0514    
                  0.0362    
                  0.0697    
                  0.0416    
               
               
                 Upper limit of 95% CI 
                  0.625     
                  0.653     
                  0.770     
                  0.418     
                  0.928     
                  0.548     
                  0.370     
                  1.07     
                  0.478     
               
               
                 OR Quartile 3 
                  0.232     
                  0.109     
                  0.190     
                  0.120     
                  0.158     
                  0.0965    
                  0.133     
                  0.211     
                  0.108     
               
               
                 p Value 
                  0.0048    
                  0.0057    
                  0.0041    
                  0.0018    
                  0.023     
                  0.0034    
                  0.0031    
                  0.059     
                  0.0055    
               
               
                 Lower limit of 95% CI 
                  0.0837    
                  0.0228    
                  0.0613    
                  0.0317    
                  0.0321    
                  0.0202    
                  0.0351    
                  0.0417    
                  0.0225    
               
               
                 Upper limit of 95% CI 
                  0.641     
                  0.525     
                  0.590     
                  0.455     
                  0.776     
                  0.462     
                  0.507     
                  1.06     
                  0.520     
               
               
                 OR Quartile 4 
                  0.167     
                  0.173     
                  0.211     
                  0.122     
                  0.234     
                  0.151     
                  0.132     
                  0.298     
                  0.165     
               
               
                 p Value 
                  0.023     
                  0.10     
                  0.050     
                  0.048     
                  0.18     
                  0.077     
                  0.057     
                  0.27     
                  0.093     
               
               
                 Lower limit of 95% CI 
                  0.0356    
                  0.0212    
                  0.0445    
                  0.0152    
                  0.0283    
                  0.0186    
                  0.0165    
                  0.0354    
                  0.0203    
               
               
                 Upper limit of 95% CI 
                  0.781     
                  1.41     
                  1.00     
                  0.980     
                  1.94     
                  1.23     
                  1.06     
                  2.52     
                  1.35     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 168 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.37  
                  2.19  
                  5.26  
                  1.59  
                  5.02  
                  1.59  
               
               
                 Average 
                  6.03  
                  2.75  
                  5.90  
                  2.23  
                  5.77  
                  2.28  
               
               
                 Stdev 
                  4.34  
                  2.44  
                  4.23  
                  2.04  
                  4.22  
                  2.12  
               
               
                 p (t-test) 
                   
                 3.2E−4 
                   
                 1.5E−4 
                   
                 5.0E−4 
               
               
                 Min 
                  0.502 
                  0.276  
                  0.366 
                  0.276 
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 54    
                 29    
                 60    
                 23    
                 62    
                 21    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  4.85  
                  1.89  
                  4.82  
                  2.19  
                  4.71  
                  1.82  
               
               
                 Average 
                  5.51  
                  2.36  
                  5.34  
                  2.50  
                  5.30  
                  2.51  
               
               
                 Stdev 
                  4.28  
                  2.26  
                  4.26  
                  2.43  
                  4.24  
                  2.54  
               
               
                 p (t-test) 
                   
                  0.0058 
                   
                  0.023 
                   
                  0.031  
               
               
                 Min 
                  0.432 
                  0.276  
                  0.366 
                  0.276 
                  0.366 
                  0.276  
               
               
                 Max 
                 20.6  
                  9.11  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 64    
                 16    
                 67    
                 13    
                 68    
                 12    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  5.37  
                  2.91  
                  5.42  
                  1.59  
                  5.36  
                  1.59  
               
               
                 Average 
                  5.93  
                  3.09  
                  5.95  
                  2.47  
                  5.90  
                  2.42  
               
               
                 Stdev 
                  4.44  
                  2.52  
                  4.31  
                  2.11  
                  4.29  
                  2.16  
               
               
                 p (t-test) 
                   
                  0.0045 
                   
                 8.9E−4 
                   
                  0.0011 
               
               
                 Min 
                  0.366 
                  0.398  
                  0.366 
                  0.398 
                  0.366 
                  0.398  
               
               
                 Max 
                 20.6  
                  9.53  
                 20.6  
                  9.11  
                 20.6  
                  9.11  
               
               
                 n (Patient) 
                 54    
                 24    
                 58    
                 20    
                 59    
                 19    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.22     
                  0.23     
                  0.27     
                  0.18     
                  0.26     
                  0.21     
                  0.20     
                  0.26     
                  0.21     
               
               
                 SE 
                  0.057     
                  0.073    
                  0.066     
                  0.058     
                  0.083     
                  0.065     
                  0.062     
                  0.086     
                  0.066     
               
               
                 p Value 
                 1.3E−6 
                 1.8E−4 
                 6.3E−4 
                 2.9E−8 
                  0.0033    
                 6.2E−6 
                 7.4E−7 
                  0.0047    
                 8.1E−6 
               
               
                 nCohort  
                 54       
                 64       
                 54       
                 60       
                 67       
                 58       
                 62       
                 68       
                 59       
               
               
                 Non-persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort Persistent 
                 29       
                 16       
                 24       
                 23       
                 13       
                 20       
                 21       
                 12       
                 19       
               
               
                 Cutoff Quartile 2 
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
                  2.05     
                  1.90     
                  2.02     
               
               
                 Sensitivity 
                 52%    
                 50%    
                 54%    
                 43%    
                 54%    
                 45%    
                 43%    
                 50%    
                 42%    
               
               
                 Specificity 
                 13%    
                 19%    
                 17%    
                 13%    
                 21%    
                 16%    
                 15%    
                 21%    
                 15%    
               
               
                 Cutoff Quartile 3 
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
                  4.01     
                  3.91     
                  4.44     
               
               
                 Sensitivity 
                 28%    
                 19%    
                 21%    
                 17%    
                 23%    
                 10%    
                 19%    
                 25%    
                 11%    
               
               
                 Specificity 
                 37%    
                 42%    
                 37%    
                 37%    
                 45%    
                 36%    
                 39%    
                 46%    
                 37%    
               
               
                 Cutoff Quartile 4 
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30     
                  6.36     
                  6.30     
                  6.30     
                  6.36     
               
               
                 Sensitivity 
                  7%    
                  6%    
                  8%    
                  4%    
                  8%    
                  5%    
                  5%    
                  8%    
                  5%    
               
               
                 Specificity 
                 65%    
                 70%    
                 67%    
                 67%    
                 72%    
                 67%    
                 68%    
                 72%    
                 68%    
               
               
                 OR Quartile 2 
                  0.160     
                  0.231     
                  0.236     
                  0.118     
                  0.308     
                  0.150     
                  0.127     
                  0.259     
                  0.131     
               
               
                 p Value 
                 8.4E−4 
                  0.014     
                  0.0086    
                 1.7E−4 
                  0.063     
                  0.0010    
                 3.0E−4 
                  0.038     
                 5.6E−4 
               
               
                 Lower limit  
                  0.0543    
                  0.0721    
                  0.0806    
                  0.0390    
                  0.0892    
                  0.0485    
                  0.0417    
                  0.0724    
                  0.0413    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  0.469     
                  0.739     
                  0.693     
                  0.359     
                  1.06     
                  0.466     
                  0.389     
                  0.928     
                  0.415     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                  0.224     
                  0.168     
                  0.155     
                  0.122     
                  0.243     
                  0.0631    
                  0.149     
                  0.279     
                  0.0700    
               
               
                 p Value 
                  0.0029    
                  0.0097    
                  0.0012    
                 5.8E−4 
                  0.044     
                 5.0E−4 
                  0.0019    
                  0.072     
                 8.1E−4 
               
               
                 Lower limit  
                  0.0838    
                  0.0437    
                  0.0500    
                  0.0367    
                  0.0614    
                  0.0133    
                  0.0446    
                  0.0695    
                  0.0147    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  0.599     
                  0.650     
                  0.479     
                  0.404     
                  0.964     
                  0.299     
                  0.495     
                  1.12     
                  0.332     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                  0.136     
                  0.158     
                  0.182     
                  0.0909    
                  0.211     
                  0.108     
                  0.105     
                  0.234     
                  0.117     
               
               
                 p Value 
                  0.011     
                  0.084     
                  0.032     
                  0.023     
                  0.15     
                  0.036     
                  0.034     
                  0.18     
                  0.044     
               
               
                 Lower limit  
                  0.0292    
                  0.0194    
                  0.0384    
                  0.0114    
                  0.0256    
                  0.0134    
                  0.0131    
                  0.0283    
                  0.0145    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  0.637     
                  1.28     
                  0.860     
                  0.724     
                  1.73     
                  0.869     
                  0.839     
                  1.94     
                  0.942     
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 24 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.555 
                  0.791 
                  0.544 
                  1.03  
                  0.532 
                  1.07  
               
               
                 Average 
                  0.769 
                  1.10  
                  0.765 
                  1.26  
                  0.761 
                  1.31  
               
               
                 Stdev 
                  0.751 
                  1.01  
                  0.736 
                  1.12  
                  0.731 
                  1.14  
               
               
                 p (t-test) 
                   
                  0.11  
                   
                  0.032 
                   
                  0.020 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.249 
                  0.108 
                  0.249 
               
               
                 Max 
                  4.86  
                  4.60  
                  4.86  
                  4.60  
                  4.86  
                  4.60  
               
               
                 n (Patient) 
                 61    
                 23    
                 68    
                 16    
                 69    
                 15    
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.567 
                  0.990 
                  0.567 
                  1.03  
                  0.561 
                  1.07  
               
               
                 Average 
                  0.860 
                  0.948 
                  0.853 
                  1.00  
                  0.848 
                  1.05  
               
               
                 Stdev 
                  0.892 
                  0.617 
                  0.882 
                  0.637 
                  0.877 
                  0.647 
               
               
                 p (t-test) 
                   
                  0.73  
                   
                  0.58  
                   
                  0.47  
               
               
                 Min 
                  0.108 
                  0.217 
                  0.108 
                  0.217 
                  0.108 
                  0.217 
               
               
                 Max 
                  4.86  
                  2.58  
                  4.86  
                  2.58  
                  4.86  
                  2.58  
               
               
                 n (Patient) 
                 67    
                 14    
                 69    
                 12    
                 70    
                 11    
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                  0.544 
                  0.979 
                  0.555 
                  1.02  
                  0.555 
                  1.02  
               
               
                 Average 
                  0.748 
                  1.21  
                  0.758 
                  1.47  
                  0.758 
                  1.47  
               
               
                 Stdev 
                  0.734 
                  1.13  
                  0.720 
                  1.36  
                  0.720 
                  1.36  
               
               
                 p (t-test) 
                   
                  0.047 
                   
                  0.013 
                   
                  0.013 
               
               
                 Min 
                  0.108 
                  0.172 
                  0.108 
                  0.249 
                  0.108 
                  0.249 
               
               
                 Max 
                  4.86  
                  4.60  
                  4.86  
                  4.60  
                  4.86  
                  4.60  
               
               
                 n (Patient) 
                 60    
                 17    
                 67    
                 10    
                 67    
                 10    
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.61     
                  0.62     
                  0.64     
                  0.68     
                  0.65     
                  0.68     
                  0.70      
                  0.67     
                  0.68     
               
               
                 SE 
                  0.071    
                  0.087    
                  0.080    
                  0.080    
                  0.092    
                  0.099    
                  0.081     
                  0.095    
                  0.099    
               
               
                 p Value 
                  0.12     
                  0.18     
                  0.086    
                  0.022    
                  0.100    
                  0.067    
                  0.015     
                  0.070    
                  0.067    
               
               
                 nCohort Non-persistent 
                 61       
                 67       
                 60       
                 68       
                 69       
                 67       
                 69        
                 70       
                 67       
               
               
                 nCohort Persistent 
                 23       
                 14       
                 17       
                 16       
                 12       
                 10       
                 15        
                 11       
                 10       
               
               
                 Cutoff Quartile 2 
                  0.372    
                  0.374    
                  0.374    
                  0.372    
                  0.374    
                  0.374    
                  0.372     
                  0.374    
                  0.374    
               
               
                 Sensitivity 
                 78%    
                 86%    
                 76%    
                 88%    
                 92%    
                 80%    
                 87%     
                 91%    
                 80%    
               
               
                 Specificity 
                 26%    
                 27%    
                 25%    
                 28%    
                 28%    
                 25%    
                 28%     
                 27%    
                 25%    
               
               
                 Cutoff Quartile 3 
                  0.614    
                  0.636    
                  0.593    
                  0.614    
                  0.636    
                  0.593    
                  0.614     
                  0.636    
                  0.593    
               
               
                 Sensitivity 
                 61%    
                 64%    
                 65%    
                 69%    
                 67%    
                 70%    
                 73%     
                 73%    
                 70%    
               
               
                 Specificity 
                 54%    
                 52%    
                 53%    
                 54%    
                 52%    
                 52%    
                 55%     
                 53%    
                 52%    
               
               
                 Cutoff Quartile 4 
                  1.04     
                  1.04     
                  1.00     
                  1.04     
                  1.04     
                  1.00     
                  1.04      
                  1.04     
                  1.00     
               
               
                 Sensitivity 
                 39%    
                 43%    
                 47%    
                 50%    
                 50%    
                 60%    
                 53%     
                 55%    
                 60%    
               
               
                 Specificity 
                 80%    
                 78%    
                 80%    
                 81%    
                 78%    
                 79%    
                 81%     
                 79%    
                 79%    
               
               
                 OR Quartile 2 
                  1.28     
                  2.20     
                  1.08     
                  2.71     
                  4.18     
                  1.36     
                  2.47      
                  3.73     
                  1.36     
               
               
                 p Value 
                  0.67     
                  0.33     
                  0.90     
                  0.21     
                  0.18     
                  0.71     
                  0.26      
                  0.22     
                  0.71     
               
               
                 Lower limit of 95% CI 
                  0.408    
                  0.449    
                  0.306    
                  0.563    
                  0.505    
                  0.263    
                  0.509     
                  0.446    
                  0.263    
               
               
                 Upper limit of 95% CI 
                  4.02     
                  10.8     
                  3.83     
                 13.1      
                 34.6      
                  7.04     
                 12.0       
                 31.1      
                  7.04     
               
               
                 OR Quartile 3 
                  1.83     
                  1.97     
                  2.10     
                  2.63     
                  2.18     
                  2.55     
                  3.37      
                  2.99     
                  2.55     
               
               
                 p Value 
                  0.22     
                  0.27     
                  0.19     
                  0.10     
                  0.24     
                  0.20     
                  0.055     
                  0.13     
                  0.20     
               
               
                 Lower limit of 95% CI 
                  0.690    
                  0.597    
                  0.686    
                  0.823    
                  0.601    
                  0.608    
                  0.977     
                  0.732    
                  0.608    
               
               
                 Upper limit of 95% CI 
                  4.87     
                  6.50     
                  6.40     
                  8.38     
                  7.92     
                 10.7     
                 11.6      
                 12.2     
                 10.7     
               
               
                 OR Quartile 4 
                  2.62     
                  2.60     
                  3.56     
                  4.23     
                  3.60     
                  5.68     
                  4.92      
                  4.40     
                  5.68     
               
               
                 p Value 
                  0.071    
                  0.12     
                  0.030    
                  0.014    
                  0.048    
                  0.015    
                  0.0081    
                  0.027    
                  0.015    
               
               
                 Lower limit of 95% CI 
                  0.920    
                  0.780    
                  1.13     
                  1.34     
                  1.01     
                  1.41     
                  1.51      
                  1.18     
                  1.41     
               
               
                 Upper limit of 95% CI 
                  7.49     
                  8.67     
                 11.2     
                 13.4     
                 12.8     
                 22.9     
                 16.0      
                 16.4     
                 22.9     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 48 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.561 
                 0.787 
                 0.555 
                 1.00 
                 0.544 
                 1.03 
               
               
                 Average 
                 0.778 
                 1.06 
                 0.773 
                 1.20 
                 0.769 
                 1.24 
               
               
                 Stdev 
                 0.754 
                 1.01 
                 0.739 
                 1.11 
                 0.734 
                 1.13 
               
               
                 p (t-test) 
                   
                 0.16 
                   
                 0.061 
                   
                 0.041 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 60 
                 24 
                 67 
                 17 
                 68 
                 16 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.567 
                 0.990 
                 0.567 
                 1.03 
                 0.561 
                 1.07 
               
               
                 Average 
                 0.860 
                 0.948 
                 0.853 
                 1.00 
                 0.848 
                 1.05 
               
               
                 Stdev 
                 0.892 
                 0.617 
                 0.882 
                 0.637 
                 0.877 
                 0.647 
               
               
                 p (t-test) 
                   
                 0.73 
                   
                 0.58 
                   
                 0.47 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 67 
                 14 
                 69 
                 12 
                 70 
                 11 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.544 
                 0.791 
                 0.555 
                 0.896 
                 0.555 
                 0.896 
               
               
                 Average 
                 0.759 
                 1.13 
                 0.768 
                 1.29 
                 0.768 
                 1.29 
               
               
                 Stdev 
                 0.744 
                 1.10 
                 0.728 
                 1.29 
                 0.728 
                 1.29 
               
               
                 p (t-test) 
                   
                 0.10 
                   
                 0.049 
                   
                 0.049 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 58 
                 19 
                 65 
                 12 
                 65 
                 12 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                   
                   
                   
               
               
                 Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.58     
                  0.62     
                  0.60     
                  0.64     
                  0.65     
                  0.62     
                  0.66     
                  0.67     
                  0.62     
               
               
                 SE 
                  0.071    
                  0.087    
                  0.077    
                  0.079    
                  0.092    
                  0.093    
                  0.081    
                  0.095    
                  0.093    
               
               
                 p Value 
                  0.24     
                  0.18     
                  0.20     
                  0.071    
                  0.100    
                  0.21     
                  0.054    
                  0.070    
                  0.21     
               
               
                 nCohort  
                 60      
                 67      
                 58      
                 67      
                 69      
                 65      
                 68      
                 70      
                 65      
               
               
                 Non-persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 nCohort  
                 24      
                 14      
                 19      
                 17      
                 12      
                 12      
                 16      
                 11      
                 12      
               
               
                 Persistent 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Cutoff Quartile 2 
                  0.372    
                  0.374    
                  0.374    
                  0.372    
                  0.374    
                  0.374    
                  0.372    
                  0.374    
                  0.374    
               
               
                 Sensitivity 
                 75%    
                 86%    
                 74%    
                 82%    
                 92%    
                 75%    
                 81%    
                 91%    
                 75%    
               
               
                 Specificity 
                 25%    
                 27%    
                 24%    
                 27%    
                 28%    
                 25%    
                 26%    
                 27%    
                 25%    
               
               
                 Cutoff Quartile 3 
                  0.614    
                  0.636    
                  0.593    
                  0.614    
                  0.636    
                  0.593    
                  0.614    
                  0.636    
                  0.593    
               
               
                 Sensitivity 
                 58%    
                 64%    
                 63%    
                 65%    
                 67%    
                 67%    
                 69%    
                 73%    
                 67%    
               
               
                 Specificity 
                 53%    
                 52%    
                 53%    
                 54%    
                 52%    
                 52%    
                 54%    
                 53%    
                 52%    
               
               
                 Cutoff Quartile 4 
                  1.04     
                  1.04     
                  1.00     
                  1.04     
                  1.04     
                  1.00     
                  1.04     
                  1.04     
                  1.00     
               
               
                 Sensitivity 
                 38%    
                 43%    
                 42%    
                 47%    
                 50%    
                 50%    
                 50%    
                 55%    
                 50%    
               
               
                 Specificity 
                 80%    
                 78%    
                 79%    
                 81%    
                 78%    
                 78%    
                 81%    
                 79%    
                 78%    
               
               
                 OR Quartile 2 
                  1.00     
                  2.20     
                  0.891    
                  1.71     
                  4.18     
                  0.980    
                  1.56     
                  3.73     
                  0.980    
               
               
                 p Value 
                  1.0     
                  0.33     
                  0.85     
                  0.44     
                  0.18     
                  0.98     
                  0.52     
                  0.22     
                  0.98     
               
               
                 Lower limit  
                  0.335    
                  0.449    
                  0.272    
                  0.440    
                  0.505    
                  0.236    
                  0.398    
                  0.446    
                  0.236    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  2.98     
                  10.8     
                  2.91     
                  6.67     
                 34.6     
                  4.07     
                  6.12     
                 31.1     
                  4.07     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 3 
                  1.60     
                  1.97     
                  1.97     
                  2.13     
                  2.18     
                  2.19     
                  2.63     
                  2.99     
                  2.19     
               
               
                 p Value 
                  0.34     
                  0.27     
                  0.21     
                  0.18     
                  0.24     
                  0.23     
                  0.10     
                  0.13     
                  0.23     
               
               
                 Lower limit  
                  0.614    
                  0.597    
                  0.678    
                  0.705    
                  0.601    
                  0.601    
                  0.823    
                  0.732    
                  0.601    
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  4.17     
                  6.50     
                  5.71     
                  6.43     
                  7.92     
                  8.01     
                  8.38     
                  12.2     
                  8.01     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 OR Quartile 4 
                  2.40     
                  2.60     
                  2.79     
                  3.69     
                  3.60     
                  3.64     
                  4.23     
                  4.40     
                  3.64     
               
               
                 p Value 
                  0.099    
                  0.12     
                  0.070    
                  0.023    
                  0.048    
                  0.047    
                  0.014    
                  0.027    
                  0.047    
               
               
                 Lower limit  
                  0.848    
                  0.780    
                  0.918    
                  1.19     
                  1.01     
                  1.02     
                  1.34     
                  1.18     
                  1.02     
               
               
                 of 95% CI 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Upper limit  
                  6.80     
                  8.67     
                  8.46     
                 11.4     
                 12.8     
                 13.1     
                 13.4     
                 16.4     
                 13.1     
               
               
                 of 95% CI 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve 
               
               
                 (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where 
               
               
                 persistence starts within 72 hours after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output 
               
               
                 RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.567 
                 0.783 
                 0.544 
                 1.03 
                 0.532 
                 1.07 
               
               
                 Average 
                 0.783 
                 1.04 
                 0.754 
                 1.24 
                 0.750 
                 1.29 
               
               
                 Stdev 
                 0.760 
                 0.993 
                 0.728 
                 1.10 
                 0.723 
                 1.11 
               
               
                 p (t-test) 
                   
                 0.21 
                   
                 0.027 
                   
                 0.017 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 59 
                 25 
                 66 
                 18 
                 67 
                 17 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.580 
                 0.979 
                 0.567 
                 1.03 
                 0.561 
                 1.07 
               
               
                 Average 
                 0.866 
                 0.918 
                 0.853 
                 1.00 
                 0.848 
                 1.05 
               
               
                 Stdev 
                 0.898 
                 0.607 
                 0.882 
                 0.637 
                 0.877 
                 0.647 
               
               
                 p (t-test) 
                   
                 0.83 
                   
                 0.58 
                   
                 0.47 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 66 
                 15 
                 69 
                 12 
                 70 
                 11 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                 Persistence  
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.787 
                 0.555 
                 0.896 
                 0.544 
                 1.00 
               
               
                 Average 
                 0.763 
                 1.10 
                 0.753 
                 1.29 
                 0.749 
                 1.35 
               
               
                 Stdev 
                 0.749 
                 1.08 
                 0.721 
                 1.23 
                 0.716 
                 1.25 
               
               
                 p (t-test) 
                   
                 0.13 
                   
                 0.033 
                   
                 0.019 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 57 
                 20 
                 63 
                 14 
                 64 
                 13 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                  0.58     
                  0.60     
                  0.59     
                  0.67      
                  0.65     
                  0.63     
                  0.68     
                  0.67     
                  0.65     
               
               
                 SE 
                  0.070    
                  0.084    
                  0.076    
                  0.076     
                  0.092    
                  0.087    
                  0.078     
                  0.095    
                  0.089    
               
               
                 p Value 
                  0.27     
                  0.23     
                  0.24     
                  0.030     
                  0.100    
                  0.13     
                  0.022     
                  0.070    
                  0.100    
               
               
                 nCohort Non-persistent 
                 59       
                 66       
                 57       
                 66        
                 69    
                 63       
                 67       
                 70       
                 64       
               
               
                 nCohort Persistent 
                 25       
                 15       
                 20       
                 18        
                 12    
                 14       
                 17       
                 11       
                 13       
               
               
                 Cutoff Quartile 2 
                  0.372    
                  0.374    
                  0.374    
                  0.372     
                  0.374    
                  0.374    
                  0.372     
                  0.374    
                  0.374    
               
               
                 Sensitivity 
                 76%    
                 87%    
                 75%    
                 83%     
                 92%    
                 79%    
                 82%    
                 91%    
                 77%    
               
               
                 Specificity 
                 25%    
                 27%    
                 25%    
                 27%     
                 28%    
                 25%    
                 27%    
                 27%    
                 25%    
               
               
                 Cutoff Quartile 3 
                  0.614    
                  0.636    
                  0.593    
                  0.614     
                  0.636    
                  0.593    
                  0.614    
                  0.636    
                  0.593    
               
               
                 Sensitivity 
                 56%    
                 60%    
                 60%    
                 67%     
                 67%    
                 64%    
                 71%    
                 73%    
                 69%    
               
               
                 Specificity 
                 53%    
                 52%    
                 53%    
                 55%     
                 52%    
                 52%    
                 55%    
                 53%    
                 53%    
               
               
                 Cutoff Quartile 4 
                  1.04     
                  1.04     
                  1.00     
                  1.04      
                  1.04     
                  1.00     
                  1.04     
                  1.04     
                  1.00     
               
               
                 Sensitivity 
                 36%    
                 40%    
                 40%    
                 50%     
                 50%    
                 50%    
                 53%    
                 55%    
                 54%    
               
               
                 Specificity 
                 80%    
                 77%    
                 79%    
                 82%     
                 78%    
                 79%    
                 82%    
                 79%    
                 80%    
               
               
                 OR Quartile 2 
                  1.08     
                  2.44     
                  0.977    
                  1.88      
                  4.18     
                  1.25     
                  1.71     
                  3.73     
                  1.11     
               
               
                 p Value 
                  0.89     
                  0.27     
                  0.97     
                  0.36      
                  0.18     
                  0.76     
                  0.44     
                  0.22     
                  0.88     
               
               
                 Lower limit of 95% CI 
                  0.363    
                  0.500    
                  0.301    
                  0.485     
                  0.505    
                  0.309    
                  0.440     
                  0.446    
                  0.272    
               
               
                 Upper limit of 95% CI 
                  3.21     
                 11.9     
                  3.17     
                  7.25      
                  34.6     
                  5.05     
                  6.67     
                 31.1     
                  4.55     
               
               
                 OR Quartile 3 
                  1.41     
                  1.59     
                  1.67     
                  2.40      
                  2.18     
                  1.98     
                  2.96     
                  2.99     
                  2.55     
               
               
                 p Value 
                  0.47     
                  0.42     
                  0.33     
                  0.12      
                  0.24     
                  0.26     
                  0.064     
                  0.13     
                  0.15     
               
               
                 Lower limit of 95% CI 
                  0.550    
                  0.510    
                  0.592    
                  0.804     
                  0.601    
                  0.596    
                  0.938     
                  0.732    
                  0.712    
               
               
                 Upper limit of 95% CI 
                  3.61     
                  4.98     
                  4.69     
                  7.16      
                  7.92     
                  6.57     
                  9.34     
                  12.2     
                  9.14     
               
               
                 OR Quartile 4 
                  2.20     
                  2.27     
                  2.50     
                  4.50      
                  3.60     
                  3.85     
                  5.16     
                  4.40     
                  4.58     
               
               
                 p Value 
                  0.13     
                  0.18     
                  0.10     
                  0.0082    
                  0.048    
                  0.029    
                  0.0048    
                  0.027    
                  0.017    
               
               
                 Lower limit of 95% CI 
                  0.784    
                  0.695    
                  0.834    
                  1.47      
                  1.01     
                  1.14     
                  1.65     
                  1.18     
                  1.31     
               
               
                 Upper limit of 95% CI 
                  6.19     
                  7.40     
                  7.50     
                 13.7      
                 12.8     
                 12.9     
                 16.1      
                 16.4     
                 16.0     
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 96 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.567 
                 0.783 
                 0.532 
                 1.00 
                 0.527 
                 1.03 
               
               
                 Average 
                 0.783 
                 1.04 
                 0.751 
                 1.23 
                 0.747 
                 1.27 
               
               
                 Stdev 
                 0.760 
                 0.993 
                 0.733 
                 1.07 
                 0.728 
                 1.08 
               
               
                 p (t-test) 
                   
                 0.21 
                   
                 0.027 
                   
                 0.018 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 59 
                 25 
                 65 
                 19 
                 66 
                 18 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.580 
                 0.979 
                 0.561 
                 1.00 
                 0.555 
                 1.03 
               
               
                 Average 
                 0.866 
                 0.918 
                 0.851 
                 1.000 
                 0.846 
                 1.04 
               
               
                 Stdev 
                 0.898 
                 0.607 
                 0.889 
                 0.610 
                 0.883 
                 0.617 
               
               
                 p (t-test) 
                   
                 0.83 
                   
                 0.57 
                   
                 0.46 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 66 
                 15 
                 68 
                 13 
                 69 
                 12 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.787 
                 0.544 
                 0.979 
                 0.532 
                 0.990 
               
               
                 Average 
                 0.763 
                 1.10 
                 0.749 
                 1.27 
                 0.745 
                 1.32 
               
               
                 Stdev 
                 0.749 
                 1.08 
                 0.726 
                 1.19 
                 0.721 
                 1.21 
               
               
                 p (t-test) 
                   
                 0.13 
                   
                 0.034 
                   
                 0.021 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 57 
                 20 
                 62 
                 15 
                 63 
                 14 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.60 
                 0.59 
                 0.67 
                 0.66 
                 0.64 
                 0.69 
                 0.68 
                 0.66 
               
               
                 SE 
                 0.070 
                 0.084 
                 0.076 
                 0.075 
                 0.088 
                 0.084 
                 0.076 
                 0.091 
                 0.086 
               
               
                 p Value 
                 0.27 
                 0.23 
                 0.24 
                 0.020 
                 0.071 
                 0.088 
                 0.014 
                 0.049 
                 0.065 
               
               
                 nCohort Non-persistent 
                 59 
                 66 
                 57 
                 65 
                 68 
                 62 
                 66 
                 69 
                 63 
               
               
                 nCohort Persistent 
                 25 
                 15 
                 20 
                 19 
                 13 
                 15 
                 18 
                 12 
                 14 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 76% 
                 87% 
                 75% 
                 84% 
                 92% 
                 80% 
                 83% 
                 92% 
                 79% 
               
               
                 Specificity 
                 25% 
                 27% 
                 25% 
                 28% 
                 28% 
                 26% 
                 27% 
                 28% 
                 25% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 56% 
                 60% 
                 60% 
                 68% 
                 69% 
                 67% 
                 72% 
                 75% 
                 71% 
               
               
                 Specificity 
                 53% 
                 52% 
                 53% 
                 55% 
                 53% 
                 53% 
                 56% 
                 54% 
                 54% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 36% 
                 40% 
                 40% 
                 47% 
                 46% 
                 47% 
                 50% 
                 50% 
                 50% 
               
               
                 Specificity 
                 80% 
                 77% 
                 79% 
                 82% 
                 78% 
                 79% 
                 82% 
                 78% 
                 79% 
               
               
                 OR Quartile 2 
                 1.08 
                 2.44 
                 0.977 
                 2.04 
                 4.65 
                 1.39 
                 1.88 
                 4.18 
                 1.25 
               
               
                 p Value 
                 0.89 
                 0.27 
                 0.97 
                 0.30 
                 0.15 
                 0.64 
                 0.36 
                 0.18 
                 0.76 
               
               
                 Lower limit of 95% CI 
                 0.363 
                 0.500 
                 0.301 
                 0.531 
                 0.565 
                 0.348 
                 0.485 
                 0.505 
                 0.309 
               
               
                 Upper limit of 95% CI 
                 3.21 
                 11.9 
                 3.17 
                 7.86 
                 38.3 
                 5.57 
                 7.25 
                 34.6 
                 5.05 
               
               
                 OR Quartile 3 
                 1.41 
                 1.59 
                 1.67 
                 2.69 
                 2.53 
                 2.28 
                 3.32 
                 3.47 
                 2.93 
               
               
                 p Value 
                 0.47 
                 0.42 
                 0.33 
                 0.074 
                 0.15 
                 0.17 
                 0.039 
                 0.079 
                 0.095 
               
               
                 Lower limit of 95% CI 
                 0.550 
                 0.510 
                 0.592 
                 0.910 
                 0.711 
                 0.697 
                 1.06 
                 0.864 
                 0.831 
               
               
                 Upper limit of 95% CI 
                 3.61 
                 4.98 
                 4.69 
                 7.95 
                 9.02 
                 7.43 
                 10.4 
                 13.9 
                 10.3 
               
               
                 OR Quartile 4 
                 2.20 
                 2.27 
                 2.50 
                 3.97 
                 3.03 
                 3.30 
                 4.50 
                 3.60 
                 3.85 
               
               
                 p Value 
                 0.13 
                 0.18 
                 0.10 
                 0.014 
                 0.078 
                 0.048 
                 0.0082 
                 0.048 
                 0.029 
               
               
                 Lower limit of 95% CI 
                 0.784 
                 0.695 
                 0.834 
                 1.33 
                 0.884 
                 1.01 
                 1.47 
                 1.01 
                 1.14 
               
               
                 Upper limit of 95% CI 
                 6.19 
                 7.40 
                 7.50 
                 11.9 
                 10.4 
                 10.8 
                 13.7 
                 12.8 
                 12.9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 168 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.791 
                 0.527 
                 1.02 
                 0.527 
                 1.02 
               
               
                 Average 
                 0.773 
                 1.04 
                 0.746 
                 1.18 
                 0.749 
                 1.21 
               
               
                 Stdev 
                 0.771 
                 0.955 
                 0.746 
                 1.01 
                 0.737 
                 1.05 
               
               
                 p (t-test) 
                   
                 0.17 
                   
                 0.038 
                   
                 0.030 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 57 
                 27 
                 62 
                 22 
                 64 
                 20 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.580 
                 0.979 
                 0.561 
                 1.00 
                 0.555 
                 1.03 
               
               
                 Average 
                 0.866 
                 0.918 
                 0.851 
                 1.000 
                 0.846 
                 1.04 
               
               
                 Stdev 
                 0.898 
                 0.607 
                 0.889 
                 0.610 
                 0.883 
                 0.617 
               
               
                 p (t-test) 
                   
                 0.83 
                   
                 0.57 
                   
                 0.46 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 66 
                 15 
                 68 
                 13 
                 69 
                 12 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.544 
                 0.791 
                 0.532 
                 0.990 
                 0.527 
                 1.00 
               
               
                 Average 
                 0.758 
                 1.10 
                 0.745 
                 1.20 
                 0.740 
                 1.24 
               
               
                 Stdev 
                 0.755 
                 1.05 
                 0.740 
                 1.10 
                 0.734 
                 1.12 
               
               
                 p (t-test) 
                   
                 0.12 
                   
                 0.048 
                   
                 0.032 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 56 
                 21 
                 59 
                 18 
                 60 
                 17 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.60 
                 0.60 
                 0.61 
                 0.67 
                 0.66 
                 0.65 
                 0.67 
                 0.68 
                 0.66 
               
               
                 SE 
                 0.068 
                 0.084 
                 0.075 
                 0.070 
                 0.088 
                 0.078 
                 0.073 
                 0.091 
                 0.079 
               
               
                 p Value 
                 0.13 
                 0.23 
                 0.16 
                 0.015 
                 0.071 
                 0.063 
                 0.023 
                 0.049 
                 0.047 
               
               
                 nCohort Non-persistent 
                 57 
                 66 
                 56 
                 62 
                 68 
                 59 
                 64 
                 69 
                 60 
               
               
                 nCohort Persistent 
                 27 
                 15 
                 21 
                 22 
                 13 
                 18 
                 20 
                 12 
                 17 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 78% 
                 87% 
                 76% 
                 82% 
                 92% 
                 78% 
                 80% 
                 92% 
                 76% 
               
               
                 Specificity 
                 26% 
                 27% 
                 25% 
                 27% 
                 28% 
                 25% 
                 27% 
                 28% 
                 25% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 59% 
                 60% 
                 62% 
                 68% 
                 69% 
                 67% 
                 70% 
                 75% 
                 71% 
               
               
                 Specificity 
                 54% 
                 52% 
                 54% 
                 56% 
                 53% 
                 54% 
                 56% 
                 54% 
                 55% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 37% 
                 40% 
                 43% 
                 45% 
                 46% 
                 50% 
                 45% 
                 50% 
                 53% 
               
               
                 Specificity 
                 81% 
                 77% 
                 80% 
                 82% 
                 78% 
                 81% 
                 81% 
                 78% 
                 82% 
               
               
                 OR Quartile 2 
                 1.25 
                 2.44 
                 1.07 
                 1.70 
                 4.65 
                 1.19 
                 1.45 
                 4.18 
                 1.08 
               
               
                 p Value 
                 0.69 
                 0.27 
                 0.91 
                 0.39 
                 0.15 
                 0.78 
                 0.56 
                 0.18 
                 0.90 
               
               
                 Lower limit of 95% CI 
                 0.424 
                 0.500 
                 0.330 
                 0.503 
                 0.565 
                 0.340 
                 0.424 
                 0.505 
                 0.306 
               
               
                 Upper limit of 95% CI 
                 3.69 
                 11.9 
                 3.44 
                 5.75 
                 38.3 
                 4.19 
                 4.94 
                 34.6 
                 3.83 
               
               
                 OR Quartile 3 
                 1.73 
                 1.59 
                 1.88 
                 2.78 
                 2.53 
                 2.37 
                 3.00 
                 3.47 
                 2.93 
               
               
                 p Value 
                 0.24 
                 0.42 
                 0.23 
                 0.051 
                 0.15 
                 0.13 
                 0.045 
                 0.079 
                 0.069 
               
               
                 Lower limit of 95% CI 
                 0.686 
                 0.510 
                 0.672 
                 0.994 
                 0.711 
                 0.784 
                 1.02 
                 0.864 
                 0.919 
               
               
                 Upper limit of 95% CI 
                 4.39 
                 4.98 
                 5.23 
                 7.77 
                 9.02 
                 7.16 
                 8.80 
                 13.9 
                 9.36 
               
               
                 OR Quartile 4 
                 2.46 
                 2.27 
                 3.07 
                 3.86 
                 3.03 
                 4.36 
                 3.55 
                 3.60 
                 5.01 
               
               
                 p Value 
                 0.084 
                 0.18 
                 0.043 
                 0.013 
                 0.078 
                 0.011 
                 0.022 
                 0.048 
                 0.0063 
               
               
                 Lower limit of 95% CI 
                 0.886 
                 0.695 
                 1.03 
                 1.34 
                 0.884 
                 1.41 
                 1.20 
                 1.01 
                 1.58 
               
               
                 Upper limit of 95% CI 
                 6.83 
                 7.40 
                 9.10 
                 11.2 
                 10.4 
                 13.5 
                 10.5 
                 12.8 
                 15.9 
               
               
                   
               
            
           
         
       
     
     Example 17. Use of Tyrosine-Protein Kinase Receptor UFO for Evaluating Renal Status in Patients Admitted to the ICU: Persistent at RIFLE I or F 
     Patients from the intensive care unit (ICU) are enrolled in the following study. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) are collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Tyrosine-protein kinase receptor UFO is measured in the earliest samples collected while the patients were in RIFLE I or F by standard immunoassay methods using commercially available assay reagents. 
     Kidney status is assessed by RIFLE criteria based on serum creatinine, urine output, or both serum creatinine and urine output. Two cohorts are defined to represent a “persistent” and a “non-persistent” population. “Persistent” indicates those patients whose minimum RIFLE stage during a period of 24, 48 or 72 hours is injury (I) or failure (F) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. “Non-persistent” indicates those patients who are not persistent at injury (I) or failure (F) and whose minimum RIFLE stage during a period of 24, 48 or 72 hours is non-injury (RIFLE 0) or risk of injury (R) where the persistence period can start from the time of sample collection to 24, 48, 72, 96 or 168 hours after sample collection. If a patient dies after injury (I) or failure (F) or is placed on renal replacement therapy (RRT) at any time from sample collection to 24, 48, 72, 96 or 168 hours after sample collection, the patient is considered “persistent”. 
     The ability to distinguish the “persistent” and “non-persistent” cohorts is determined using receiver operating characteristic (ROC) analysis. 
     
       
         
           
               
             
               
                 TABLE 17.1 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC)  
               
               
                 in urine samples for the “persistent” and “non-persistent” cohorts where persistence starts within 24 hours 
               
               
                 after sample collection and renal status is assessed by 
               
               
                 serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.79 
                 2.78 
                 5.32 
                 2.16 
                 4.88 
                 1.59 
               
               
                 Average 
                 6.32 
                 3.68 
                 6.03 
                 2.52 
                 5.86 
                 2.34 
               
               
                 Stdev 
                 4.29 
                 3.52 
                 4.37 
                 1.91 
                 4.28 
                 1.92 
               
               
                 p (t-test) 
                   
                 0.0028 
                   
                 1.5E−4 
                   
                 3.0E−4 
               
               
                 Min 
                 0.432 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.6 
                 7.34 
                 20.6 
                 7.34 
               
               
                 n (Patient) 
                 38 
                 45 
                 56 
                 27 
                 60 
                 23 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.16 
                 1.64 
                 4.87 
                 2.19 
                 4.85 
                 1.89 
               
               
                 Average 
                 5.94 
                 2.24 
                 5.66 
                 2.38 
                 5.54 
                 2.24 
               
               
                 Stdev 
                 4.32 
                 1.98 
                 4.32 
                 2.13 
                 4.26 
                 2.20 
               
               
                 p (t-test) 
                   
                 1.7E−4 
                   
                 0.0021 
                   
                 0.0038 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.6 
                 9.11 
                 20.6 
                 9.11 
                 20.6 
                 9.11 
               
               
                 n (Patient) 
                 57 
                 23 
                 61 
                 19 
                 64 
                 16 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 4.84 
                 4.01 
                 4.84 
                 2.78 
                 4.84 
                 2.78 
               
               
                 Average 
                 5.51 
                 4.69 
                 5.39 
                 4.48 
                 5.41 
                 4.39 
               
               
                 Stdev 
                 4.46 
                 3.90 
                 3.96 
                 4.46 
                 3.99 
                 4.43 
               
               
                 p (t-test) 
                   
                 0.39 
                   
                 0.35 
                   
                 0.31 
               
               
                 Min 
                 0.366 
                 0.489 
                 0.366 
                 0.489 
                 0.366 
                 0.489 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 35 
                 43 
                 49 
                 29 
                 51 
                 27 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.28 
                 0.19 
                 0.45 
                 0.22 
                 0.22 
                 0.40 
                 0.21 
                 0.21 
                 0.40 
               
               
                 SE 
                 0.056 
                 0.058 
                 0.065 
                 0.058 
                 0.068 
                 0.068 
                 0.061 
                 0.072 
                 0.069 
               
               
                 p Value 
                 1.1E−4 
                 7.0E−8 
                 0.44 
                 9.9E−7 
                 4.6E−5 
                 0.15 
                 1.5E−6 
                 6.7E−5 
                 0.13 
               
               
                 nCohort Non-persistent 
                 38 
                 57 
                 35 
                 56 
                 61 
                 49 
                 60 
                 64 
                 51 
               
               
                 nCohort Persistent 
                 45 
                 23 
                 43 
                 27 
                 19 
                 29 
                 23 
                 16 
                 27 
               
               
                 Cutoff Quartile 2 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
               
               
                 Sensitivity 
                 67% 
                 48% 
                 74% 
                 52% 
                 53% 
                 62% 
                 48% 
                 50% 
                 63% 
               
               
                 Specificity 
                 16% 
                 14% 
                 26% 
                 14% 
                 18% 
                 18% 
                 15% 
                 19% 
                 20% 
               
               
                 Cutoff Quartile 3 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
               
               
                 Sensitivity 
                 38% 
                 13% 
                 47% 
                 26% 
                 16% 
                 41% 
                 22% 
                 12% 
                 41% 
               
               
                 Specificity 
                 34% 
                 35% 
                 46% 
                 38% 
                 39% 
                 45% 
                 38% 
                 41% 
                 45% 
               
               
                 Cutoff Quartile 4 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
               
               
                 Sensitivity 
                 11% 
                  4% 
                 16% 
                  4% 
                  5% 
                 17% 
                  4% 
                  6% 
                 15% 
               
               
                 Specificity 
                 58% 
                 67% 
                 63% 
                 64% 
                 69% 
                 69% 
                 67% 
                 70% 
                 69% 
               
               
                 OR Quartile 2 
                 0.375 
                 0.150 
                 1.01 
                 0.179 
                 0.244 
                 0.368 
                 0.162 
                 0.231 
                 0.415 
               
               
                 p Value 
                 0.072 
                 7.8E−4 
                 0.99 
                 0.0015 
                 0.013 
                 0.060 
                 9.7E−4 
                 0.014 
                 0.098 
               
               
                 Lower limit of 95% CI 
                 0.129 
                 0.0494 
                 0.362 
                 0.0620 
                 0.0804 
                 0.130 
                 0.0548 
                 0.0721 
                 0.146 
               
               
                 Upper limit of 95% CI 
                 1.09 
                 0.453 
                 2.80 
                 0.520 
                 0.743 
                 1.04 
                 0.477 
                 0.739 
                 1.18 
               
               
                 OR Quartile 3 
                 0.316 
                 0.0811 
                 0.732 
                 0.210 
                 0.122 
                 0.575 
                 0.173 
                 0.0977 
                 0.565 
               
               
                 p Value 
                 0.012 
                 2.1E−4 
                 0.50 
                 0.0026 
                 0.0020 
                 0.24 
                 0.0021 
                 0.0036 
                 0.24 
               
               
                 Lower limit of 95% CI 
                 0.128 
                 0.0214 
                 0.299 
                 0.0760 
                 0.0320 
                 0.227 
                 0.0564 
                 0.0205 
                 0.219 
               
               
                 Upper limit of 95% CI 
                 0.778 
                 0.307 
                 1.79 
                 0.580 
                 0.463 
                 1.46 
                 0.529 
                 0.467 
                 1.45 
               
               
                 OR Quartile 4 
                 0.172 
                 0.0909 
                 0.329 
                 0.0692 
                 0.123 
                 0.472 
                 0.0909 
                 0.158 
                 0.380 
               
               
                 p Value 
                 0.0023 
                 0.024 
                 0.040 
                 0.011 
                 0.049 
                 0.20 
                 0.023 
                 0.084 
                 0.12 
               
               
                 Lower limit of 95% CI 
                 0.0555 
                 0.0114 
                 0.114 
                 0.00873 
                 0.0153 
                 0.151 
                 0.0114 
                 0.0194 
                 0.113 
               
               
                 Upper limit of 95% CI 
                 0.533 
                 0.726 
                 0.951 
                 0.549 
                 0.988 
                 1.48 
                 0.724 
                 1.28 
                 1.28 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.2 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where persistence starts within 48 hours  
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.90 
                 3.03 
                 5.54 
                 2.19 
                 5.02 
                 2.16 
               
               
                 Average 
                 6.86 
                 3.77 
                 6.24 
                 2.83 
                 6.04 
                 2.73 
               
               
                 Stdev 
                 4.39 
                 3.47 
                 4.46 
                 2.25 
                 4.37 
                 2.32 
               
               
                 p (t-test) 
                   
                 6.7E−4 
                   
                 1.1E−4 
                   
                 2.8E−4 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.6 
                 9.11 
                 20.6 
                 9.11 
               
               
                 n (Patient) 
                 30 
                 53 
                 50 
                 33 
                 54 
                 29 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.49 
                 1.64 
                 5.02 
                 2.32 
                 4.87 
                 1.89 
               
               
                 Average 
                 6.21 
                 2.27 
                 5.79 
                 2.47 
                 5.62 
                 2.31 
               
               
                 Stdev 
                 4.35 
                 1.91 
                 4.38 
                 2.04 
                 4.29 
                 2.15 
               
               
                 p (t-test) 
                   
                 2.5E−5 
                   
                 0.0010 
                   
                 0.0023 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.6 
                 9.11 
                 20.6 
                 9.11 
                 20.6 
                 9.11 
               
               
                 n (Patient) 
                 53 
                 27 
                 58 
                 22 
                 62 
                 18 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 4.88 
                 4.01 
                 4.88 
                 3.03 
                 4.88 
                 3.03 
               
               
                 Average 
                 5.74 
                 4.65 
                 5.60 
                 4.35 
                 5.60 
                 4.27 
               
               
                 Stdev 
                 4.61 
                 3.84 
                 3.99 
                 4.31 
                 4.02 
                 4.27 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.19 
                   
                 0.16 
               
               
                 Min 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 29 
                 49 
                 44 
                 34 
                 46 
                 32 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.25 
                 0.17 
                 0.43 
                 0.23 
                 0.23 
                 0.37 
                 0.23 
                 0.22 
                 0.37 
               
               
                 SE 
                 0.053 
                 0.053 
                 0.066 
                 0.055 
                 0.064 
                 0.064 
                 0.058 
                 0.069 
                 0.065 
               
               
                 p Value 
                 4.1E−6 
                 3.6E−10 
                 0.27 
                 1.1E−6 
                 1.9E−5 
                 0.047 
                 3.6E−6 
                 3.9E−5 
                 0.042 
               
               
                 nCohort Non-persistent 
                 30 
                 53 
                 29 
                 50 
                 58 
                 44 
                 54 
                 62 
                 46 
               
               
                 nCohort Persistent 
                 53 
                 27 
                 49 
                 33 
                 22 
                 34 
                 29 
                 18 
                 32 
               
               
                 Cutoff Quartile 2 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
               
               
                 Sensitivity 
                 66% 
                 48% 
                 73% 
                 55% 
                 55% 
                 62% 
                 52% 
                 50% 
                 62% 
               
               
                 Specificity 
                 10% 
                 11% 
                 24% 
                 12% 
                 17% 
                 16% 
                 13% 
                 18% 
                 17% 
               
               
                 Cutoff Quartile 3 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
               
               
                 Sensitivity 
                 40% 
                 15% 
                 47% 
                 30% 
                 18% 
                 41% 
                 28% 
                 17% 
                 41% 
               
               
                 Specificity 
                 30% 
                 32% 
                 45% 
                 36% 
                 38% 
                 43% 
                 37% 
                 40% 
                 43% 
               
               
                 Cutoff Quartile 4 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
               
               
                 Sensitivity 
                 13% 
                  4% 
                 18% 
                  6% 
                  5% 
                 18% 
                  7% 
                  6% 
                 16% 
               
               
                 Specificity 
                 53% 
                 64% 
                 62% 
                 62% 
                 67% 
                 68% 
                 65% 
                 69% 
                 67% 
               
               
                 OR Quartile 2 
                 0.216 
                 0.119 
                 0.881 
                 0.164 
                 0.250 
                 0.306 
                 0.160 
                 0.216 
                 0.351 
               
               
                 p Value 
                 0.023 
                 2.4E−4 
                 0.82 
                 0.0012 
                 0.012 
                 0.029 
                 8.4E−4 
                 0.0078 
                 0.050 
               
               
                 Lower limit of 95% CI 
                 0.0576 
                 0.0380 
                 0.305 
                 0.0548 
                 0.0848 
                 0.106 
                 0.0543 
                 0.0696 
                 0.123 
               
               
                 Upper limit of 95% CI 
                 0.810 
                 0.369 
                 2.55 
                 0.489 
                 0.737 
                 0.885 
                 0.469 
                 0.668 
                 0.998 
               
               
                 OR Quartile 3 
                 0.281 
                 0.0821 
                 0.719 
                 0.245 
                 0.136 
                 0.532 
                 0.224 
                 0.135 
                 0.526 
               
               
                 p Value 
                 0.0093 
                 5.0E−5 
                 0.48 
                 0.0033 
                 0.0012 
                 0.17 
                 0.0029 
                 0.0034 
                 0.17 
               
               
                 Lower limit of 95% CI 
                 0.108 
                 0.0245 
                 0.286 
                 0.0955 
                 0.0406 
                 0.215 
                 0.0838 
                 0.0354 
                 0.211 
               
               
                 Upper limit of 95% CI 
                 0.731 
                 0.275 
                 1.81 
                 0.626 
                 0.454 
                 1.32 
                 0.599 
                 0.516 
                 1.31 
               
               
                 OR Quartile 4 
                 0.174 
                 0.0688 
                 0.368 
                 0.105 
                 0.0977 
                 0.459 
                 0.136 
                 0.133 
                 0.383 
               
               
                 p Value 
                 0.0014 
                 0.011 
                 0.060 
                 0.0042 
                 0.028 
                 0.16 
                 0.011 
                 0.058 
                 0.098 
               
               
                 Lower limit of 95% CI 
                 0.0596 
                 0.00864 
                 0.130 
                 0.0226 
                 0.0122 
                 0.155 
                 0.0292 
                 0.0165 
                 0.123 
               
               
                 Upper limit of 95% CI 
                 0.507 
                 0.548 
                 1.04 
                 0.491 
                 0.782 
                 1.36 
                 0.637 
                 1.07 
                 1.19 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.3 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where persistence starts within 72 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.79 
                 3.15 
                 5.54 
                 2.44 
                 5.02 
                 2.19 
               
               
                 Average 
                 6.74 
                 3.89 
                 6.22 
                 3.05 
                 6.02 
                 2.99 
               
               
                 Stdev 
                 4.42 
                 3.55 
                 4.49 
                 2.52 
                 4.39 
                 2.62 
               
               
                 p (t-test) 
                   
                 0.0020 
                   
                 3.1E−4 
                   
                 8.0E−4 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.6 
                 10.3 
                 20.6 
                 10.3 
               
               
                 n (Patient) 
                 29 
                 54 
                 48 
                 35 
                 52 
                 31 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.42 
                 1.92 
                 4.88 
                 2.44 
                 4.87 
                 2.19 
               
               
                 Average 
                 6.13 
                 2.56 
                 5.71 
                 2.81 
                 5.55 
                 2.74 
               
               
                 Stdev 
                 4.35 
                 2.42 
                 4.37 
                 2.58 
                 4.28 
                 2.78 
               
               
                 p (t-test) 
                   
                 1.4E−4 
                   
                 0.0040 
                   
                 0.0090 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.6 
                 10.3 
                 20.6 
                 10.3 
                 20.6 
                 10.3 
               
               
                 n (Patient) 
                 52 
                 28 
                 57 
                 23 
                 61 
                 19 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 4.88 
                 4.01 
                 4.88 
                 3.03 
                 4.88 
                 3.03 
               
               
                 Average 
                 5.74 
                 4.65 
                 5.66 
                 4.32 
                 5.66 
                 4.23 
               
               
                 Stdev 
                 4.61 
                 3.84 
                 4.01 
                 4.25 
                 4.04 
                 4.21 
               
               
                 p (t-test) 
                   
                 0.26 
                   
                 0.16 
                   
                 0.13 
               
               
                 Min 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 29 
                 49 
                 43 
                 35 
                 45 
                 33 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.27 
                 0.20 
                 0.43 
                 0.25 
                 0.26 
                 0.37 
                 0.26 
                 0.26 
                 0.36 
               
               
                 SE 
                 0.055 
                 0.055 
                 0.066 
                 0.056 
                 0.066 
                 0.064 
                 0.058 
                 0.071 
                 0.064 
               
               
                 p Value 
                 3.9E−5 
                 4.9E−8 
                 0.27 
                 8.7E−6 
                 2.4E−4 
                 0.036 
                 3.0E−5 
                 5.8E−4 
                 0.032 
               
               
                 nCohort Non-persistent 
                 29 
                 52 
                 29 
                 48 
                 57 
                 43 
                 52 
                 61 
                 45 
               
               
                 nCohort Persistent 
                 54 
                 28 
                 49 
                 35 
                 23 
                 35 
                 31 
                 19 
                 33 
               
               
                 Cutoff Quartile 2 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
               
               
                 Sensitivity 
                 67% 
                 50% 
                 73% 
                 57% 
                 57% 
                 63% 
                 55% 
                 53% 
                 64% 
               
               
                 Specificity 
                 10% 
                 12% 
                 24% 
                 12% 
                 18% 
                 16% 
                 13% 
                 18% 
                 18% 
               
               
                 Cutoff Quartile 3 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
               
               
                 Sensitivity 
                 41% 
                 18% 
                 47% 
                 31% 
                 22% 
                 40% 
                 29% 
                 21% 
                 39% 
               
               
                 Specificity 
                 31% 
                 33% 
                 45% 
                 35% 
                 39% 
                 42% 
                 37% 
                 41% 
                 42% 
               
               
                 Cutoff Quartile 4 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
               
               
                 Sensitivity 
                 15% 
                  7% 
                 18% 
                  9% 
                  9% 
                 17% 
                 10% 
                 11% 
                 15% 
               
               
                 Specificity 
                 55% 
                 65% 
                 62% 
                 62% 
                 68% 
                 67% 
                 65% 
                 70% 
                 67% 
               
               
                 OR Quartile 2 
                 0.231 
                 0.130 
                 0.881 
                 0.190 
                 0.277 
                 0.329 
                 0.189 
                 0.244 
                 0.378 
               
               
                 p Value 
                 0.030 
                 4.0E−4 
                 0.82 
                 0.0028 
                 0.019 
                 0.040 
                 0.0022 
                 0.013 
                 0.068 
               
               
                 Lower limit of 95% CI 
                 0.0615 
                 0.0422 
                 0.305 
                 0.0643 
                 0.0948 
                 0.114 
                 0.0651 
                 0.0804 
                 0.133 
               
               
                 Upper limit of 95% CI 
                 0.866 
                 0.403 
                 2.55 
                 0.564 
                 0.807 
                 0.951 
                 0.548 
                 0.743 
                 1.07 
               
               
                 OR Quartile 3 
                 0.309 
                 0.106 
                 0.719 
                 0.251 
                 0.175 
                 0.480 
                 0.236 
                 0.185 
                 0.475 
               
               
                 p Value 
                 0.016 
                 9.3E−5 
                 0.48 
                 0.0035 
                 0.0024 
                 0.11 
                 0.0031 
                 0.0065 
                 0.11 
               
               
                 Lower limit of 95% CI 
                 0.119 
                 0.0342 
                 0.286 
                 0.0995 
                 0.0567 
                 0.194 
                 0.0903 
                 0.0549 
                 0.190 
               
               
                 Upper limit of 95% CI 
                 0.805 
                 0.326 
                 1.81 
                 0.635 
                 0.538 
                 1.19 
                 0.615 
                 0.624 
                 1.19 
               
               
                 OR Quartile 4 
                 0.214 
                 0.145 
                 0.368 
                 0.156 
                 0.206 
                 0.429 
                 0.202 
                 0.281 
                 0.357 
               
               
                 p Value 
                 0.0040 
                 0.015 
                 0.060 
                 0.0058 
                 0.047 
                 0.13 
                 0.018 
                 0.11 
                 0.076 
               
               
                 Lower limit of 95% CI 
                 0.0750 
                 0.0309 
                 0.130 
                 0.0417 
                 0.0436 
                 0.145 
                 0.0540 
                 0.0588 
                 0.115 
               
               
                 Upper limit of 95% CI 
                 0.611 
                 0.683 
                 1.04 
                 0.585 
                 0.976 
                 1.27 
                 0.758 
                 1.34 
                 1.11 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.4 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where persistence starts within 96 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.79 
                 3.36 
                 5.58 
                 2.47 
                 5.32 
                 2.44 
               
               
                 Average 
                 6.66 
                 4.03 
                 6.24 
                 3.29 
                 6.09 
                 3.23 
               
               
                 Stdev 
                 4.46 
                 3.63 
                 4.53 
                 2.79 
                 4.43 
                 2.88 
               
               
                 p (t-test) 
                   
                 0.0053 
                   
                 7.7E−4 
                   
                 0.0012 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 27 
                 56 
                 45 
                 38 
                 48 
                 35 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.32 
                 2.32 
                 4.87 
                 2.51 
                 4.85 
                 2.47 
               
               
                 Average 
                 6.04 
                 2.95 
                 5.61 
                 3.26 
                 5.48 
                 3.30 
               
               
                 Stdev 
                 4.37 
                 2.88 
                 4.38 
                 3.05 
                 4.32 
                 3.22 
               
               
                 p (t-test) 
                   
                 9.4E−4 
                   
                 0.018 
                   
                 0.035 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 50 
                 30 
                 55 
                 25 
                 58 
                 22 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 4.88 
                 4.18 
                 5.16 
                 3.28 
                 5.02 
                 3.44 
               
               
                 Average 
                 5.58 
                 4.78 
                 5.68 
                 4.43 
                 5.60 
                 4.49 
               
               
                 Stdev 
                 4.64 
                 3.88 
                 4.06 
                 4.20 
                 4.04 
                 4.24 
               
               
                 p (t-test) 
                   
                 0.42 
                   
                 0.19 
                   
                 0.24 
               
               
                 Min 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 27 
                 51 
                 39 
                 39 
                 40 
                 38 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.29 
                 0.24 
                 0.45 
                 0.27 
                 0.30 
                 0.38 
                 0.27 
                 0.31 
                 0.39 
               
               
                 SE 
                 0.057 
                 0.058 
                 0.068 
                 0.056 
                 0.067 
                 0.063 
                 0.057 
                 0.070 
                 0.064 
               
               
                 p Value 
                 2.4E−4 
                 6.1E−6 
                 0.45 
                 3.9E−5 
                 0.0033 
                 0.050 
                 5.3E−5 
                 0.0079 
                 0.073 
               
               
                 nCohort Non-persistent 
                 27 
                 50 
                 27 
                 45 
                 55 
                 39 
                 48 
                 58 
                 40 
               
               
                 nCohort Persistent 
                 56 
                 30 
                 51 
                 38 
                 25 
                 39 
                 35 
                 22 
                 38 
               
               
                 Cutoff Quartile 2 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
               
               
                 Sensitivity 
                 68% 
                 53% 
                 75% 
                 61% 
                 60% 
                 67% 
                 57% 
                 59% 
                 66% 
               
               
                 Specificity 
                 11% 
                 12% 
                 26% 
                 13% 
                 18% 
                 18% 
                 12% 
                 19% 
                 18% 
               
               
                 Cutoff Quartile 3 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
               
               
                 Sensitivity 
                 43% 
                 23% 
                 47% 
                 34% 
                 28% 
                 38% 
                 31% 
                 27% 
                 39% 
               
               
                 Specificity 
                 33% 
                 34% 
                 44% 
                 36% 
                 40% 
                 38% 
                 35% 
                 41% 
                 40% 
               
               
                 Cutoff Quartile 4 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
               
               
                 Sensitivity 
                 16% 
                 10% 
                 20% 
                 11% 
                 12% 
                 18% 
                 11% 
                 14% 
                 18% 
               
               
                 Specificity 
                 56% 
                 66% 
                 63% 
                 62% 
                 69% 
                 67% 
                 65% 
                 71% 
                 68% 
               
               
                 OR Quartile 2 
                 0.264 
                 0.156 
                 1.02 
                 0.236 
                 0.333 
                 0.438 
                 0.190 
                 0.338 
                 0.408 
               
               
                 p Value 
                 0.049 
                 0.0011 
                 0.97 
                 0.0086 
                 0.041 
                 0.12 
                 0.0028 
                 0.048 
                 0.096 
               
               
                 Lower limit of 95% CI 
                 0.0702 
                 0.0511 
                 0.352 
                 0.0803 
                 0.116 
                 0.152 
                 0.0643 
                 0.116 
                 0.142 
               
               
                 Upper limit of 95% CI 
                 0.993 
                 0.475 
                 2.97 
                 0.693 
                 0.956 
                 1.26 
                 0.564 
                 0.989 
                 1.17 
               
               
                 OR Quartile 3 
                 0.375 
                 0.157 
                 0.711 
                 0.287 
                 0.259 
                 0.391 
                 0.251 
                 0.265 
                 0.435 
               
               
                 p Value 
                 0.045 
                 4.2E−4 
                 0.48 
                 0.0069 
                 0.0099 
                 0.043 
                 0.0035 
                 0.015 
                 0.072 
               
               
                 Lower limit of 95% CI 
                 0.144 
                 0.0560 
                 0.279 
                 0.116 
                 0.0929 
                 0.157 
                 0.0995 
                 0.0904 
                 0.175 
               
               
                 Upper limit of 95% CI 
                 0.979 
                 0.439 
                 1.82 
                 0.710 
                 0.724 
                 0.973 
                 0.635 
                 0.775 
                 1.08 
               
               
                 OR Quartile 4 
                 0.239 
                 0.216 
                 0.415 
                 0.194 
                 0.305 
                 0.437 
                 0.235 
                 0.381 
                 0.469 
               
               
                 p Value 
                 0.0071 
                 0.024 
                 0.098 
                 0.0073 
                 0.081 
                 0.12 
                 0.018 
                 0.16 
                 0.16 
               
               
                 Lower limit of 95% CI 
                 0.0845 
                 0.0571 
                 0.146 
                 0.0584 
                 0.0802 
                 0.152 
                 0.0710 
                 0.0995 
                 0.163 
               
               
                 Upper limit of 95% CI 
                 0.678 
                 0.814 
                 1.18 
                 0.642 
                 1.16 
                 1.26 
                 0.779 
                 1.46 
                 1.35 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.5 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in urine samples for the “persistent” and “non-persistent” cohorts where persistence starts within 168 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.79 
                 3.36 
                 5.69 
                 2.47 
                 5.54 
                 2.44 
               
               
                 Average 
                 6.78 
                 4.07 
                 6.42 
                 3.24 
                 6.25 
                 3.18 
               
               
                 Stdev 
                 4.50 
                 3.64 
                 4.55 
                 2.73 
                 4.45 
                 2.82 
               
               
                 p (t-test) 
                   
                 0.0048 
                   
                 2.6E−4 
                   
                 4.6E−4 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 25 
                 58 
                 43 
                 40 
                 46 
                 37 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 5.49 
                 2.44 
                 4.88 
                 2.65 
                 4.87 
                 2.47 
               
               
                 Average 
                 6.07 
                 2.99 
                 5.64 
                 3.30 
                 5.58 
                 3.24 
               
               
                 Stdev 
                 4.41 
                 2.84 
                 4.42 
                 3.00 
                 4.35 
                 3.11 
               
               
                 p (t-test) 
                   
                 8.7E−4 
                   
                 0.017 
                   
                 0.020 
               
               
                 Min 
                 0.502 
                 0.276 
                 0.366 
                 0.276 
                 0.366 
                 0.276 
               
               
                 Max 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
                 20.6 
                 11.5 
               
               
                 n (Patient) 
                 49 
                 31 
                 54 
                 26 
                 56 
                 24 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 4.74 
                 4.30 
                 5.16 
                 3.43 
                 5.16 
                 3.43 
               
               
                 Average 
                 5.46 
                 4.85 
                 5.65 
                 4.52 
                 5.65 
                 4.46 
               
               
                 Stdev 
                 4.69 
                 3.89 
                 4.12 
                 4.15 
                 4.08 
                 4.19 
               
               
                 p (t-test) 
                   
                 0.55 
                   
                 0.23 
                   
                 0.21 
               
               
                 Min 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
                 0.366 
                 0.398 
               
               
                 Max 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
                 20.5 
                 20.6 
               
               
                 n (Patient) 
                 26 
                 52 
                 37 
                 41 
                 39 
                 39 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.28 
                 0.24 
                 0.47 
                 0.25 
                 0.31 
                 0.39 
                 0.25 
                 0.30 
                 0.38 
               
               
                 SE 
                 0.057 
                 0.058 
                 0.069 
                 0.054 
                 0.066 
                 0.064 
                 0.055 
                 0.067 
                 0.063 
               
               
                 p Value 
                 1.6E−4 
                 7.9E−6 
                 0.64 
                 4.3E−6 
                 0.0039 
                 0.077 
                 7.0E−6 
                 0.0036 
                 0.059 
               
               
                 nCohort Non-persistent 
                 25 
                 49 
                 26 
                 43 
                 54 
                 37 
                 46 
                 56 
                 39 
               
               
                 nCohort Persistent 
                 58 
                 31 
                 52 
                 40 
                 26 
                 41 
                 37 
                 24 
                 39 
               
               
                 Cutoff Quartile 2 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
                 2.05 
                 1.90 
                 2.02 
               
               
                 Sensitivity 
                 67% 
                 55% 
                 75% 
                 60% 
                 62% 
                 68% 
                 57% 
                 58% 
                 67% 
               
               
                 Specificity 
                  8% 
                 12% 
                 27% 
                 12% 
                 19% 
                 19% 
                 11% 
                 18% 
                 18% 
               
               
                 Cutoff Quartile 3 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
                 4.01 
                 3.91 
                 4.44 
               
               
                 Sensitivity 
                 43% 
                 26% 
                 48% 
                 32% 
                 31% 
                 39% 
                 30% 
                 29% 
                 38% 
               
               
                 Specificity 
                 32% 
                 35% 
                 46% 
                 33% 
                 41% 
                 38% 
                 33% 
                 41% 
                 38% 
               
               
                 Cutoff Quartile 4 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
                 6.30 
                 6.30 
                 6.36 
               
               
                 Sensitivity 
                 17% 
                 10% 
                 21% 
                 10% 
                 12% 
                 20% 
                 11% 
                 12% 
                 18% 
               
               
                 Specificity 
                 56% 
                 65% 
                 65% 
                 60% 
                 69% 
                 68% 
                 63% 
                 70% 
                 67% 
               
               
                 OR Quartile 2 
                 0.178 
                 0.169 
                 1.11 
                 0.197 
                 0.364 
                 0.503 
                 0.160 
                 0.304 
                 0.438 
               
               
                 p Value 
                 0.029 
                 0.0017 
                 0.85 
                 0.0048 
                 0.058 
                 0.20 
                 0.0015 
                 0.028 
                 0.12 
               
               
                 Lower limit of 95% CI 
                 0.0381 
                 0.0559 
                 0.379 
                 0.0640 
                 0.128 
                 0.175 
                 0.0515 
                 0.105 
                 0.152 
               
               
                 Upper limit of 95% CI 
                 0.837 
                 0.514 
                 3.22 
                 0.609 
                 1.04 
                 1.44 
                 0.497 
                 0.880 
                 1.26 
               
               
                 OR Quartile 3 
                 0.357 
                 0.185 
                 0.794 
                 0.232 
                 0.306 
                 0.390 
                 0.205 
                 0.287 
                 0.391 
               
               
                 p Value 
                 0.041 
                 9.0E−4 
                 0.63 
                 0.0019 
                 0.019 
                 0.043 
                 9.0E−4 
                 0.017 
                 0.043 
               
               
                 Lower limit of 95% CI 
                 0.133 
                 0.0682 
                 0.309 
                 0.0927 
                 0.113 
                 0.156 
                 0.0802 
                 0.103 
                 0.157 
               
               
                 Upper limit of 95% CI 
                 0.958 
                 0.501 
                 2.04 
                 0.583 
                 0.826 
                 0.972 
                 0.522 
                 0.803 
                 0.973 
               
               
                 OR Quartile 4 
                 0.265 
                 0.202 
                 0.507 
                 0.170 
                 0.284 
                 0.505 
                 0.207 
                 0.328 
                 0.437 
               
               
                 p Value 
                 0.013 
                 0.018 
                 0.20 
                 0.0038 
                 0.064 
                 0.20 
                 0.0099 
                 0.10 
                 0.12 
               
               
                 Lower limit of 95% CI 
                 0.0934 
                 0.0534 
                 0.178 
                 0.0512 
                 0.0748 
                 0.179 
                 0.0624 
                 0.0861 
                 0.152 
               
               
                 Upper limit of 95% CI 
                 0.752 
                 0.761 
                 1.44 
                 0.564 
                 1.08 
                 1.42 
                 0.685 
                 1.25 
                 1.26 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.6 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 24 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.647 
                 0.505 
                 0.980 
                 0.532 
                 0.791 
               
               
                 Average 
                 0.738 
                 0.974 
                 0.686 
                 1.21 
                 0.783 
                 1.06 
               
               
                 Stdev 
                 0.602 
                 1.01 
                 0.546 
                 1.17 
                 0.768 
                 0.990 
               
               
                 p (t-test) 
                   
                 0.20 
                   
                 0.0066 
                   
                 0.18 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 2.99 
                 4.86 
                 2.99 
                 4.86 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 41 
                 43 
                 56 
                 28 
                 61 
                 23 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.527 
                 1.00 
                 0.522 
                 1.03 
                 0.532 
                 1.03 
               
               
                 Average 
                 0.771 
                 1.14 
                 0.767 
                 1.21 
                 0.835 
                 1.01 
               
               
                 Stdev 
                 0.767 
                 0.996 
                 0.759 
                 1.03 
                 0.908 
                 0.599 
               
               
                 p (t-test) 
                   
                 0.080 
                   
                 0.044 
                   
                 0.43 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 58 
                 23 
                 61 
                 20 
                 63 
                 18 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.669 
                 0.522 
                 0.713 
                 0.532 
                 0.713 
               
               
                 Average 
                 0.830 
                 0.869 
                 0.800 
                 0.937 
                 0.802 
                 0.945 
               
               
                 Stdev 
                 0.899 
                 0.816 
                 0.816 
                 0.918 
                 0.802 
                 0.950 
               
               
                 p (t-test) 
                   
                 0.84 
                   
                 0.50 
                   
                 0.49 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 37 
                 40 
                 49 
                 28 
                 51 
                 26 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.56 
                 0.67 
                 0.54 
                 0.66 
                 0.71 
                 0.56 
                 0.61 
                 0.68 
                 0.55 
               
               
                 SE 
                 0.063 
                 0.070 
                 0.066 
                 0.065 
                 0.071 
                 0.069 
                 0.071 
                 0.076 
                 0.070 
               
               
                 p Value 
                 0.31 
                 0.015 
                 0.50 
                 0.011 
                 0.0030 
                 0.36 
                 0.11 
                 0.019 
                 0.49 
               
               
                 nCohort Non-persistent 
                 41 
                 58 
                 37 
                 56 
                 61 
                 49 
                 61 
                 63 
                 51 
               
               
                 nCohort Persistent 
                 43 
                 23 
                 40 
                 28 
                 20 
                 28 
                 23 
                 18 
                 26 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 77% 
                 87% 
                 75% 
                 82% 
                 95% 
                 75% 
                 83% 
                 94% 
                 73% 
               
               
                 Specificity 
                 27% 
                 29% 
                 24% 
                 29% 
                 31% 
                 24% 
                 28% 
                 30% 
                 24% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 53% 
                 65% 
                 55% 
                 64% 
                 70% 
                 61% 
                 61% 
                 67% 
                 62% 
               
               
                 Specificity 
                 54% 
                 55% 
                 54% 
                 57% 
                 56% 
                 55% 
                 54% 
                 54% 
                 55% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 30% 
                 48% 
                 30% 
                 43% 
                 50% 
                 36% 
                 39% 
                 50% 
                 35% 
               
               
                 Specificity 
                 80% 
                 83% 
                 78% 
                 84% 
                 82% 
                 80% 
                 80% 
                 81% 
                 78% 
               
               
                 OR Quartile 2 
                 1.21 
                 2.76 
                 0.964 
                 1.84 
                 8.60 
                 0.973 
                 1.84 
                 7.34 
                 0.835 
               
               
                 p Value 
                 0.71 
                 0.14 
                 0.95 
                 0.29 
                 0.043 
                 0.96 
                 0.33 
                 0.061 
                 0.74 
               
               
                 Lower limit of 95% CI 
                 0.450 
                 0.725 
                 0.342 
                 0.596 
                 1.07 
                 0.332 
                 0.545 
                 0.910 
                 0.283 
               
               
                 Upper limit of 95% CI 
                 3.25 
                 10.5 
                 2.72 
                 5.68 
                 69.0 
                 2.85 
                 6.18 
                 59.2 
                 2.46 
               
               
                 OR Quartile 3 
                 1.33 
                 2.31 
                 1.44 
                 2.40 
                 2.94 
                 1.90 
                 1.83 
                 2.34 
                 1.95 
               
               
                 p Value 
                 0.51 
                 0.10 
                 0.43 
                 0.067 
                 0.051 
                 0.18 
                 0.22 
                 0.13 
                 0.18 
               
               
                 Lower limit of 95% CI 
                 0.565 
                 0.847 
                 0.586 
                 0.940 
                 0.996 
                 0.738 
                 0.690 
                 0.782 
                 0.743 
               
               
                 Upper limit of 95% CI 
                 3.14 
                 6.29 
                 3.53 
                 6.12 
                 8.67 
                 4.88 
                 4.87 
                 7.03 
                 5.11 
               
               
                 OR Quartile 4 
                 1.79 
                 4.40 
                 1.55 
                 3.92 
                 4.55 
                 2.17 
                 2.62 
                 4.25 
                 1.93 
               
               
                 p Value 
                 0.26 
                 0.0064 
                 0.40 
                 0.0096 
                 0.0066 
                 0.14 
                 0.071 
                 0.011 
                 0.22 
               
               
                 Lower limit of 95% CI 
                 0.651 
                 1.52 
                 0.552 
                 1.39 
                 1.52 
                 0.766 
                 0.920 
                 1.39 
                 0.675 
               
               
                 Upper limit of 95% CI 
                 4.91 
                 12.8 
                 4.37 
                 11.0 
                 13.6 
                 6.13 
                 7.49 
                 13.0 
                 5.49 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.7 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 48 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.561 
                 0.645 
                 0.479 
                 0.980 
                 0.522 
                 0.791 
               
               
                 Average 
                 0.759 
                 0.920 
                 0.669 
                 1.14 
                 0.778 
                 1.01 
               
               
                 Stdev 
                 0.649 
                 0.936 
                 0.561 
                 1.08 
                 0.800 
                 0.901 
               
               
                 p (t-test) 
                   
                 0.40 
                   
                 0.011 
                   
                 0.23 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 2.99 
                 4.86 
                 2.99 
                 4.86 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 32 
                 52 
                 50 
                 34 
                 55 
                 29 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.527 
                 1.00 
                 0.503 
                 1.04 
                 0.522 
                 1.05 
               
               
                 Average 
                 0.769 
                 1.09 
                 0.758 
                 1.17 
                 0.825 
                 1.03 
               
               
                 Stdev 
                 0.789 
                 0.936 
                 0.774 
                 0.970 
                 0.920 
                 0.569 
               
               
                 p (t-test) 
                   
                 0.11 
                   
                 0.048 
                   
                 0.35 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 54 
                 27 
                 58 
                 23 
                 61 
                 20 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.561 
                 0.644 
                 0.507 
                 0.691 
                 0.527 
                 0.691 
               
               
                 Average 
                 0.840 
                 0.857 
                 0.780 
                 0.944 
                 0.782 
                 0.951 
               
               
                 Stdev 
                 0.938 
                 0.802 
                 0.821 
                 0.895 
                 0.805 
                 0.921 
               
               
                 p (t-test) 
                   
                 0.93 
                   
                 0.41 
                   
                 0.40 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 30 
                 47 
                 44 
                 33 
                 46 
                 31 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.55 
                 0.67 
                 0.53 
                 0.68 
                 0.72 
                 0.57 
                 0.63 
                 0.70 
                 0.56 
               
               
                 SE 
                 0.064 
                 0.066 
                 0.068 
                 0.061 
                 0.067 
                 0.066 
                 0.066 
                 0.072 
                 0.067 
               
               
                 p Value 
                 0.43 
                 0.0093 
                 0.70 
                 0.0035 
                 8.2E−4 
                 0.27 
                 0.052 
                 0.0043 
                 0.37 
               
               
                 nCohort Non-persistent 
                 32 
                 54 
                 30 
                 50 
                 58 
                 44 
                 55 
                 61 
                 46 
               
               
                 nCohort Persistent 
                 52 
                 27 
                 47 
                 34 
                 23 
                 33 
                 29 
                 20 
                 31 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 77% 
                 89% 
                 74% 
                 82% 
                 96% 
                 76% 
                 83% 
                 95% 
                 74% 
               
               
                 Specificity 
                 28% 
                 31% 
                 23% 
                 30% 
                 33% 
                 25% 
                 29% 
                 31% 
                 24% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 52% 
                 63% 
                 53% 
                 65% 
                 70% 
                 61% 
                 62% 
                 70% 
                 61% 
               
               
                 Specificity 
                 53% 
                 56% 
                 53% 
                 60% 
                 57% 
                 57% 
                 56% 
                 56% 
                 57% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 29% 
                 44% 
                 30% 
                 41% 
                 48% 
                 36% 
                 38% 
                 50% 
                 35% 
               
               
                 Specificity 
                 81% 
                 83% 
                 80% 
                 86% 
                 83% 
                 82% 
                 82% 
                 82% 
                 80% 
               
               
                 OR Quartile 2 
                 1.30 
                 3.68 
                 0.888 
                 2.00 
                 10.7 
                 1.04 
                 1.97 
                 8.60 
                 0.904 
               
               
                 p Value 
                 0.60 
                 0.055 
                 0.83 
                 0.20 
                 0.025 
                 0.94 
                 0.24 
                 0.043 
                 0.85 
               
               
                 Lower limit of 95% CI 
                 0.477 
                 0.972 
                 0.304 
                 0.687 
                 1.34 
                 0.365 
                 0.639 
                 1.07 
                 0.316 
               
               
                 Upper limit of 95% CI 
                 3.56 
                 13.9 
                 2.59 
                 5.83 
                 85.6 
                 2.97 
                 6.07 
                 69.0 
                 2.59 
               
               
                 OR Quartile 3 
                 1.22 
                 2.13 
                 1.30 
                 2.75 
                 3.02 
                 2.02 
                 2.11 
                 2.94 
                 2.06 
               
               
                 p Value 
                 0.65 
                 0.12 
                 0.58 
                 0.028 
                 0.035 
                 0.13 
                 0.11 
                 0.051 
                 0.13 
               
               
                 Lower limit of 95% CI 
                 0.507 
                 0.824 
                 0.519 
                 1.12 
                 1.08 
                 0.808 
                 0.842 
                 0.996 
                 0.813 
               
               
                 Upper limit of 95% CI 
                 2.96 
                 5.48 
                 3.25 
                 6.78 
                 8.44 
                 5.07 
                 5.30 
                 8.67 
                 5.21 
               
               
                 OR Quartile 4 
                 1.76 
                 4.00 
                 1.70 
                 4.30 
                 4.40 
                 2.57 
                 2.75 
                 4.55 
                 2.26 
               
               
                 p Value 
                 0.30 
                 0.0092 
                 0.34 
                 0.0065 
                 0.0064 
                 0.076 
                 0.051 
                 0.0066 
                 0.12 
               
               
                 Lower limit of 95% CI 
                 0.602 
                 1.41 
                 0.570 
                 1.50 
                 1.52 
                 0.905 
                 0.996 
                 1.52 
                 0.803 
               
               
                 Upper limit of 95% CI 
                 5.13 
                 11.4 
                 5.05 
                 12.3 
                 12.8 
                 7.30 
                 7.60 
                 13.6 
                 6.37 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.8 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 72 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.567 
                 0.643 
                 0.474 
                 0.979 
                 0.484 
                 0.791 
               
               
                 Average 
                 0.767 
                 0.913 
                 0.672 
                 1.12 
                 0.760 
                 1.03 
               
               
                 Stdev 
                 0.658 
                 0.929 
                 0.566 
                 1.07 
                 0.796 
                 0.893 
               
               
                 p (t-test) 
                   
                 0.44 
                   
                 0.015 
                   
                 0.16 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 2.99 
                 4.86 
                 2.99 
                 4.86 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 31 
                 53 
                 49 
                 35 
                 53 
                 31 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.522 
                 0.991 
                 0.484 
                 1.02 
                 0.505 
                 1.04 
               
               
                 Average 
                 0.774 
                 1.07 
                 0.762 
                 1.14 
                 0.830 
                 1.01 
               
               
                 Stdev 
                 0.796 
                 0.924 
                 0.780 
                 0.957 
                 0.927 
                 0.565 
               
               
                 p (t-test) 
                   
                 0.14 
                   
                 0.065 
                   
                 0.42 
               
               
                 Min 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
                 0.108 
                 0.217 
               
               
                 Max 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 53 
                 28 
                 57 
                 24 
                 60 
                 21 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.561 
                 0.644 
                 0.492 
                 0.713 
                 0.522 
                 0.713 
               
               
                 Average 
                 0.840 
                 0.857 
                 0.751 
                 0.975 
                 0.755 
                 0.984 
               
               
                 Stdev 
                 0.938 
                 0.802 
                 0.808 
                 0.900 
                 0.792 
                 0.925 
               
               
                 p (t-test) 
                   
                 0.93 
                   
                 0.26 
                   
                 0.25 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 30 
                 47 
                 43 
                 34 
                 45 
                 32 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.55 
                 0.67 
                 0.53 
                 0.67 
                 0.71 
                 0.60 
                 0.64 
                 0.69 
                 0.58 
               
               
                 SE 
                 0.065 
                 0.065 
                 0.068 
                 0.061 
                 0.066 
                 0.066 
                 0.064 
                 0.071 
                 0.067 
               
               
                 p Value 
                 0.45 
                 0.012 
                 0.70 
                 0.0042 
                 0.0012 
                 0.15 
                 0.026 
                 0.0061 
                 0.22 
               
               
                 nCohort Non-persistent 
                 31 
                 53 
                 30 
                 49 
                 57 
                 43 
                 53 
                 60 
                 45 
               
               
                 nCohort Persistent 
                 53 
                 28 
                 47 
                 35 
                 24 
                 34 
                 31 
                 21 
                 32 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 77% 
                 89% 
                 74% 
                 83% 
                 96% 
                 76% 
                 84% 
                 95% 
                 75% 
               
               
                 Specificity 
                 29% 
                 32% 
                 23% 
                 31% 
                 33% 
                 26% 
                 30% 
                 32% 
                 24% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 51% 
                 61% 
                 53% 
                 63% 
                 67% 
                 62% 
                 61% 
                 67% 
                 62% 
               
               
                 Specificity 
                 52% 
                 55% 
                 53% 
                 59% 
                 56% 
                 58% 
                 57% 
                 55% 
                 58% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 28% 
                 43% 
                 30% 
                 40% 
                 46% 
                 38% 
                 39% 
                 48% 
                 38% 
               
               
                 Specificity 
                 81% 
                 83% 
                 80% 
                 86% 
                 82% 
                 84% 
                 83% 
                 82% 
                 82% 
               
               
                 OR Quartile 2 
                 1.40 
                 3.94 
                 0.888 
                 2.13 
                 11.5 
                 1.12 
                 2.25 
                 9.27 
                 0.971 
               
               
                 p Value 
                 0.51 
                 0.043 
                 0.83 
                 0.16 
                 0.021 
                 0.84 
                 0.16 
                 0.036 
                 0.96 
               
               
                 Lower limit of 95% CI 
                 0.510 
                 1.04 
                 0.304 
                 0.732 
                 1.44 
                 0.392 
                 0.732 
                 1.16 
                 0.340 
               
               
                 Upper limit of 95% CI 
                 3.83 
                 14.9 
                 2.59 
                 6.21 
                 91.7 
                 3.18 
                 6.91 
                 74.2 
                 2.77 
               
               
                 OR Quartile 3 
                 1.11 
                 1.87 
                 1.30 
                 2.45 
                 2.56 
                 2.24 
                 2.07 
                 2.44 
                 2.28 
               
               
                 p Value 
                 0.82 
                 0.19 
                 0.58 
                 0.048 
                 0.065 
                 0.085 
                 0.12 
                 0.092 
                 0.082 
               
               
                 Lower limit of 95% CI 
                 0.456 
                 0.736 
                 0.519 
                 1.01 
                 0.945 
                 0.895 
                 0.836 
                 0.864 
                 0.901 
               
               
                 Upper limit of 95% CI 
                 2.69 
                 4.74 
                 3.25 
                 5.98 
                 6.94 
                 5.63 
                 5.10 
                 6.92 
                 5.77 
               
               
                 OR Quartile 4 
                 1.64 
                 3.67 
                 1.70 
                 4.00 
                 3.98 
                 3.18 
                 3.09 
                 4.05 
                 2.78 
               
               
                 p Value 
                 0.36 
                 0.014 
                 0.34 
                 0.0095 
                 0.010 
                 0.033 
                 0.030 
                 0.011 
                 0.056 
               
               
                 Lower limit of 95% CI 
                 0.563 
                 1.30 
                 0.570 
                 1.40 
                 1.39 
                 1.10 
                 1.12 
                 1.38 
                 0.974 
               
               
                 Upper limit of 95% CI 
                 4.81 
                 10.3 
                 5.05 
                 11.4 
                 11.4 
                 9.23 
                 8.55 
                 11.9 
                 7.91 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.9 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in  
               
               
                 EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 96 hours after sample collection 
               
               
                 and renal status is assessed by serum creatinine (sCr) only, . 
               
               
                 urine output (UO) only, or serum creatinine or urine output RIFLE criteria 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.602 
                 0.618 
                 0.484 
                 0.791 
                 0.479 
                 0.885 
               
               
                 Average 
                 0.781 
                 0.902 
                 0.689 
                 1.07 
                 0.757 
                 1.01 
               
               
                 Stdev 
                 0.664 
                 0.924 
                 0.572 
                 1.06 
                 0.815 
                 0.861 
               
               
                 p (t-test) 
                   
                 0.53 
                   
                 0.036 
                   
                 0.18 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 2.99 
                 4.86 
                 2.99 
                 4.86 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 30 
                 54 
                 47 
                 37 
                 50 
                 34 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.980 
                 0.522 
                 0.991 
                 0.522 
                 0.991 
               
               
                 Average 
                 0.794 
                 1.01 
                 0.781 
                 1.07 
                 0.848 
                 0.941 
               
               
                 Stdev 
                 0.805 
                 0.916 
                 0.788 
                 0.950 
                 0.945 
                 0.569 
               
               
                 p (t-test) 
                   
                 0.27 
                   
                 0.15 
                   
                 0.65 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 51 
                 30 
                 55 
                 26 
                 57 
                 24 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.567 
                 0.644 
                 0.507 
                 0.691 
                 0.492 
                 0.713 
               
               
                 Average 
                 0.858 
                 0.846 
                 0.770 
                 0.936 
                 0.756 
                 0.957 
               
               
                 Stdev 
                 0.950 
                 0.797 
                 0.830 
                 0.877 
                 0.824 
                 0.881 
               
               
                 p (t-test) 
                   
                 0.95 
                   
                 0.40 
                   
                 0.31 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 29 
                 48 
                 40 
                 37 
                 41 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.53 
                 0.62 
                 0.51 
                 0.63 
                 0.66 
                 0.56 
                 0.65 
                 0.64 
                 0.59 
               
               
                 SE 
                 0.066 
                 0.066 
                 0.068 
                 0.062 
                 0.067 
                 0.066 
                 0.062 
                 0.070 
                 0.065 
               
               
                 p Value 
                 0.62 
                 0.078 
                 0.92 
                 0.031 
                 0.019 
                 0.32 
                 0.019 
                 0.042 
                 0.18 
               
               
                 nCohort Non-persistent 
                 30 
                 51 
                 29 
                 47 
                 55 
                 40 
                 50 
                 57 
                 41 
               
               
                 nCohort Persistent 
                 54 
                 30 
                 48 
                 37 
                 26 
                 37 
                 34 
                 24 
                 36 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 76% 
                 83% 
                 73% 
                 78% 
                 88% 
                 73% 
                 82% 
                 88% 
                 75% 
               
               
                 Specificity 
                 27% 
                 29% 
                 21% 
                 28% 
                 31% 
                 22% 
                 30% 
                 30% 
                 24% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 50% 
                 57% 
                 52% 
                 59% 
                 62% 
                 59% 
                 62% 
                 62% 
                 61% 
               
               
                 Specificity 
                 50% 
                 53% 
                 52% 
                 57% 
                 55% 
                 57% 
                 58% 
                 54% 
                 59% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 28% 
                 40% 
                 29% 
                 38% 
                 42% 
                 35% 
                 38% 
                 42% 
                 36% 
               
               
                 Specificity 
                 80% 
                 82% 
                 79% 
                 85% 
                 82% 
                 82% 
                 84% 
                 81% 
                 83% 
               
               
                 OR Quartile 2 
                 1.15 
                 2.08 
                 0.702 
                 1.39 
                 3.43 
                 0.784 
                 2.00 
                 2.98 
                 0.968 
               
               
                 p Value 
                 0.79 
                 0.20 
                 0.53 
                 0.53 
                 0.070 
                 0.65 
                 0.20 
                 0.11 
                 0.95 
               
               
                 Lower limit of 95% CI 
                 0.413 
                 0.671 
                 0.234 
                 0.505 
                 0.905 
                 0.278 
                 0.687 
                 0.782 
                 0.343 
               
               
                 Upper limit of 95% CI 
                 3.19 
                 6.47 
                 2.11 
                 3.81 
                 13.0 
                 2.21 
                 5.83 
                 11.3 
                 2.73 
               
               
                 OR Quartile 3 
                 1.00 
                 1.47 
                 1.16 
                 1.98 
                 1.92 
                 1.98 
                 2.23 
                 1.99 
                 2.22 
               
               
                 p Value 
                 1.0 
                 0.40 
                 0.75 
                 0.13 
                 0.18 
                 0.14 
                 0.078 
                 0.17 
                 0.087 
               
               
                 Lower limit of 95% CI 
                 0.410 
                 0.594 
                 0.463 
                 0.826 
                 0.741 
                 0.801 
                 0.915 
                 0.748 
                 0.890 
               
               
                 Upper limit of 95% CI 
                 2.44 
                 3.65 
                 2.93 
                 4.75 
                 4.97 
                 4.92 
                 5.44 
                 5.28 
                 5.53 
               
               
                 OR Quartile 4 
                 1.54 
                 3.11 
                 1.58 
                 3.48 
                 3.30 
                 2.55 
                 3.25 
                 2.99 
                 2.75 
               
               
                 p Value 
                 0.43 
                 0.030 
                 0.41 
                 0.019 
                 0.024 
                 0.083 
                 0.024 
                 0.040 
                 0.062 
               
               
                 Lower limit of 95% CI 
                 0.525 
                 1.12 
                 0.529 
                 1.23 
                 1.17 
                 0.886 
                 1.17 
                 1.05 
                 0.951 
               
               
                 Upper limit of 95% CI 
                 4.51 
                 8.68 
                 4.71 
                 9.86 
                 9.31 
                 7.36 
                 9.06 
                 8.49 
                 7.93 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17.10 
               
               
                   
               
               
                 Comparison of marker levels and the area under the ROC curve (AUC) in EDTA samples for the “persistent” and “non-persistent” cohorts where persistence starts within 168 hours 
               
               
                 after sample collection and renal status is assessed by serum creatinine (sCr) only, urine output (UO) only, or serum creatinine or urine output RIFLE criteria. 
               
               
                   
               
             
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.602 
                 0.618 
                 0.484 
                 0.738 
                 0.479 
                 0.765 
               
               
                 Average 
                 0.802 
                 0.887 
                 0.698 
                 1.04 
                 0.768 
                 0.980 
               
               
                 Stdev 
                 0.682 
                 0.910 
                 0.582 
                 1.04 
                 0.830 
                 0.845 
               
               
                 p (t-test) 
                   
                 0.66 
                   
                 0.059 
                   
                 0.25 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 2.99 
                 4.86 
                 2.99 
                 4.86 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 28 
                 56 
                 45 
                 39 
                 48 
                 36 
               
               
                   
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.555 
                 0.980 
                 0.522 
                 0.991 
                 0.522 
                 0.991 
               
               
                 Average 
                 0.794 
                 1.01 
                 0.781 
                 1.07 
                 0.848 
                 0.941 
               
               
                 Stdev 
                 0.805 
                 0.916 
                 0.788 
                 0.950 
                 0.945 
                 0.569 
               
               
                 p (t-test) 
                   
                 0.27 
                   
                 0.15 
                   
                 0.65 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.86 
                 2.58 
               
               
                 n (Patient) 
                 51 
                 30 
                 55 
                 26 
                 57 
                 24 
               
               
                   
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
            
               
                   
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Persistence Period 
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
                 Non-persistent 
                 Persistent  
               
               
                 Duration (hr) 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
                 Cohort 
               
               
                   
               
               
                 Median 
                 0.580 
                 0.643 
                 0.539 
                 0.647 
                 0.507 
                 0.691 
               
               
                 Average 
                 0.876 
                 0.835 
                 0.793 
                 0.905 
                 0.767 
                 0.940 
               
               
                 Stdev 
                 0.962 
                 0.792 
                 0.845 
                 0.865 
                 0.832 
                 0.875 
               
               
                 p (t-test) 
                   
                 0.84 
                   
                 0.57 
                   
                 0.38 
               
               
                 Min 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
                 0.108 
                 0.172 
               
               
                 Max 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
                 4.86 
                 4.60 
               
               
                 n (Patient) 
                 28 
                 49 
                 38 
                 39 
                 40 
                 37 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Persistence Period 
                 24 
                 48 
                 72 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Duration (hr) 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.52 
                 0.62 
                 0.49 
                 0.62 
                 0.66 
                 0.53 
                 0.63 
                 0.64 
                 0.57 
               
               
                 SE 
                 0.067 
                 0.066 
                 0.069 
                 0.062 
                 0.067 
                 0.066 
                 0.062 
                 0.070 
                 0.066 
               
               
                 p Value 
                 0.79 
                 0.078 
                 0.87 
                 0.057 
                 0.019 
                 0.65 
                 0.037 
                 0.042 
                 0.28 
               
               
                 nCohort Non-persistent 
                 28 
                 51 
                 28 
                 45 
                 55 
                 38 
                 48 
                 57 
                 40 
               
               
                 nCohort Persistent 
                 56 
                 30 
                 49 
                 39 
                 26 
                 39 
                 36 
                 24 
                 37 
               
               
                 Cutoff Quartile 2 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
                 0.372 
                 0.374 
                 0.374 
               
               
                 Sensitivity 
                 75% 
                 83% 
                 71% 
                 77% 
                 88% 
                 69% 
                 81% 
                 88% 
                 73% 
               
               
                 Specificity 
                 25% 
                 29% 
                 18% 
                 27% 
                 31% 
                 18% 
                 29% 
                 30% 
                 22% 
               
               
                 Cutoff Quartile 3 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
                 0.614 
                 0.636 
                 0.593 
               
               
                 Sensitivity 
                 50% 
                 57% 
                 51% 
                 59% 
                 62% 
                 56% 
                 61% 
                 62% 
                 59% 
               
               
                 Specificity 
                 50% 
                 53% 
                 50% 
                 58% 
                 55% 
                 55% 
                 58% 
                 54% 
                 57% 
               
               
                 Cutoff Quartile 4 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
                 1.04 
                 1.04 
                 1.00 
               
               
                 Sensitivity 
                 27% 
                 40% 
                 29% 
                 36% 
                 42% 
                 33% 
                 36% 
                 42% 
                 35% 
               
               
                 Specificity 
                 79% 
                 82% 
                 79% 
                 84% 
                 82% 
                 82% 
                 83% 
                 81% 
                 82% 
               
               
                 OR Quartile 2 
                 1.00 
                 2.08 
                 0.543 
                 1.21 
                 3.43 
                 0.508 
                 1.71 
                 2.98 
                 0.784 
               
               
                 p Value 
                 1.0 
                 0.20 
                 0.30 
                 0.70 
                 0.070 
                 0.21 
                 0.31 
                 0.11 
                 0.65 
               
               
                 Lower limit of 95% CI 
                 0.351 
                 0.671 
                 0.172 
                 0.448 
                 0.905 
                 0.175 
                 0.607 
                 0.782 
                 0.278 
               
               
                 Upper limit of 95% CI 
                 2.85 
                 6.47 
                 1.71 
                 3.28 
                 13.0 
                 1.47 
                 4.80 
                 11.3 
                 2.21 
               
               
                 OR Quartile 3 
                 1.00 
                 1.47 
                 1.04 
                 1.97 
                 1.92 
                 1.60 
                 2.20 
                 1.99 
                 1.98 
               
               
                 p Value 
                 1.0 
                 0.40 
                 0.93 
                 0.13 
                 0.18 
                 0.31 
                 0.080 
                 0.17 
                 0.14 
               
               
                 Lower limit of 95% CI 
                 0.404 
                 0.594 
                 0.412 
                 0.824 
                 0.741 
                 0.650 
                 0.911 
                 0.748 
                 0.801 
               
               
                 Upper limit of 95% CI 
                 2.48 
                 3.65 
                 2.64 
                 4.70 
                 4.97 
                 3.93 
                 5.32 
                 5.28 
                 4.92 
               
               
                 OR Quartile 4 
                 1.34 
                 3.11 
                 1.47 
                 3.04 
                 3.30 
                 2.21 
                 2.83 
                 2.99 
                 2.55 
               
               
                 p Value 
                 0.59 
                 0.030 
                 0.49 
                 0.036 
                 0.024 
                 0.14 
                 0.046 
                 0.040 
                 0.083 
               
               
                 Lower limit of 95% CI 
                 0.456 
                 1.12 
                 0.491 
                 1.08 
                 1.17 
                 0.770 
                 1.02 
                 1.05 
                 0.886 
               
               
                 Upper limit of 95% CI 
                 3.95 
                 8.68 
                 4.38 
                 8.59 
                 9.31 
                 6.37 
                 7.83 
                 8.49 
                 7.36 
               
               
                   
               
            
           
         
       
     
     Example 18. AKI Biomarkers in ICU Patients 
     Patients from the intensive care unit (ICU) are enrolled in the following study. Each patient is classified by kidney status as non-injury (0), risk of injury (R), injury (I), and failure (F) according to the maximum stage reached within 7 days of enrollment as determined by the RIFLE criteria. EDTA anti-coagulated blood samples (10 mL) and urine samples (50 mL) are collected from each patient at enrollment, at 12 (±1), 24 (±2), 36 (±2), 48 (±2), 60 (±2), 72 (±2), and 84 (±2) hours after enrollment, and thereafter daily up to day 7 while the subject is hospitalized. C-C motif chemokine 14, C-C motif chemokine 16, and Tyrosine-protein kinase receptor UFO are measured by standard immunoassay methods using commercially available assay reagents in the urine samples and the plasma component of the blood samples collected. 
     Two cohorts are defined to represent a “diseased” and a “normal” population. While these terms are used for convenience, “diseased” and “normal” simply represent two cohorts for comparison (say RIFLE 0 vs RIFLE R, I and F; RIFLE 0 vs RIFLE R; RIFLE 0 and R vs RIFLE I and F; etc.). The time “prior max stage” represents the time at which a sample is collected, relative to the time a particular patient reaches the lowest disease stage as defined for that cohort, binned into three groups which are +/−12 hours. For example, “24 hr prior” which uses 0 vs R, I, F as the two cohorts would mean 24 hr (+/−12 hours) prior to reaching stage R (or I if no sample at R, or F if no sample at R or I). 
     A receiver operating characteristic (ROC) curve is generated for each biomarker and the area under the ROC curve (AUC) is determined. Patients in Cohort 2 are also separated according to the reason for adjudication to cohort 2 as being based on serum creatinine measurements (sCr), being based on urine output (UO), or being based on either serum creatinine measurements or urine output. Using the same example discussed above (0 vs R, I, F), for those patients adjudicated to stage R, I, or F on the basis of serum creatinine measurements alone, the stage 0 cohort may include patients adjudicated to stage R, I, or F on the basis of urine output; for those patients adjudicated to stage R, I, or F on the basis of urine output alone, the stage 0 cohort may include patients adjudicated to stage R, I, or F on the basis of serum creatinine measurements; and for those patients adjudicated to stage R, I, or F on the basis of serum creatinine measurements or urine output, the stage 0 cohort contains only patients in stage 0 for both serum creatinine measurements and urine output. Also, in the data for patients adjudicated on the basis of serum creatinine measurements or urine output, the adjudication method which yielded the most severe RIFLE stage is used. 
     The ability to distinguish cohort 1 from Cohort 2 is determined using ROC analysis. SE is the standard error of the AUC, n is the number of sample or individual patients (“pts,” as indicated). Standard errors are calculated as described in Hanley, J. A., and McNeil, B. J., The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology (1982) 143: 29-36; p values are calculated with a two-tailed Z-test. An AUC &lt;0.5 is indicative of a negative going marker for the comparison, and an AUC &gt;0.5 is indicative of a positive going marker for the comparison. 
     Various biomarker threshold (or “cutoff”) concentrations are selected, and the associated sensitivity and specificity for distinguishing cohort 1 from cohort 2 are determined. OR is the odds ratio calculated for the particular cutoff concentration, and 95% CI is the confidence interval for the odds ratio. 
     
       
         
           
               
             
               
                 TABLE 18.1 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 1 
               
               
                 (patients that did not progress beyond RIFLE stage 0) and in urine samples collected from 
               
               
                 subjects at 0, 24 hours, and 48 hours prior to reaching stage R, I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 C-C motif chemokine 14 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage  
                 24 hr prior to AKI stage  
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.368 
                 0.472 
                 0.368 
                 0.381 
                 0.368 
                 0.387 
               
               
                 Average 
                 0.696 
                 1.03 
                 0.696 
                 0.784 
                 0.696 
                 0.959 
               
               
                 Stdev 
                 1.07 
                 1.45 
                 1.07 
                 1.46 
                 1.07 
                 1.72 
               
               
                 p(t-test) 
                   
                 1.7E−4 
                   
                 0.41 
                   
                 0.082 
               
               
                 Min 
                 0.00865 
                 2.08E−6 
                 0.00865 
                 0.000797 
                 0.00865 
                 0.0465 
               
               
                 Max 
                 8.80 
                 8.57 
                 8.80 
                 10.4 
                 8.80 
                 9.42 
               
               
                 n (Samp) 
                 528 
                 287 
                 528 
                 152 
                 528 
                 67 
               
               
                 n (Patient) 
                 137 
                 287 
                 137 
                 152 
                 137 
                 67 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage  
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.414 
                 0.781 
                 0.414 
                 0.481 
                 0.414 
                 0.519 
               
               
                 Average 
                 0.758 
                 1.68 
                 0.758 
                 1.40 
                 0.758 
                 1.43 
               
               
                 Stdev 
                 1.07 
                 2.15 
                 1.07 
                 2.10 
                 1.07 
                 2.40 
               
               
                 p(t-test) 
                   
                 2.8E−14 
                   
                 4.3E−6 
                   
                 1.1E−4 
               
               
                 Min 
                 0.00229 
                 2.08E−6 
                 0.00229 
                 0.000797 
                 0.00229 
                 0.0516 
               
               
                 Max 
                 8.80 
                 8.78 
                 8.80 
                 10.4 
                 8.80 
                 9.42 
               
               
                 n (Samp) 
                 1187 
                 109 
                 1187 
                 74 
                 1187 
                 45 
               
               
                 n (Patient) 
                 315 
                 109 
                 315 
                 74 
                 315 
                 45 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.403 
                 0.461 
                 0.403 
                 0.372 
                 0.403 
                 0.387 
               
               
                 Average 
                 0.880 
                 1.09 
                 0.880 
                 0.778 
                 0.880 
                 1.13 
               
               
                 Stdev 
                 1.42 
                 1.54 
                 1.42 
                 1.32 
                 1.42 
                 2.03 
               
               
                 p(t-test) 
                   
                 0.046 
                   
                 0.43 
                   
                 0.18 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Min 
                 2.08E−6 
                 0.0157 
                 2.08E−6 
                 0.0404 
                 2.08E−6 
                 0.00229 
               
               
                 Max 
                 10.4 
                 7.28 
                 10.4 
                 9.26 
                 10.4 
                 9.39 
               
               
                 n (Samp) 
                 685 
                 261 
                 685 
                 147 
                 685 
                 69 
               
               
                 n (Patient) 
                 172 
                 261 
                 172 
                 147 
                 172 
                 69 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.59 
                 0.65 
                 0.56 
                 0.51 
                 0.59 
                 0.48 
                 0.53 
                 0.58 
                 0.50 
               
               
                 SE 
                 0.021 
                 0.030 
                 0.021 
                 0.027 
                 0.036 
                 0.026 
                 0.038 
                 0.045 
                 0.037 
               
               
                 P 
                 2.8E−5 
                 7.6E−7 
                 0.0061 
                 0.63 
                 0.010 
                 0.56 
                 0.42 
                 0.087 
                 0.89 
               
               
                 nCohort 1 
                 528 
                 1187 
                 685 
                 528 
                 1187 
                 685 
                 528 
                 1187 
                 685 
               
               
                 nCohort 2 
                 287 
                 109 
                 261 
                 152 
                 74 
                 147 
                 67 
                 45 
                 69 
               
               
                 Cutoff 1 
                 0.302 
                 0.375 
                 0.300 
                 0.256 
                 0.355 
                 0.253 
                 0.272 
                 0.334 
                 0.272 
               
               
                 Sens 1 
                 70% 
                 71% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 71% 
                 71% 
               
               
                 Spec 1 
                 41% 
                 45% 
                 38% 
                 35% 
                 43% 
                 32% 
                 38% 
                 40% 
                 35% 
               
               
                 Cutoff 2 
                 0.241 
                 0.297 
                 0.239 
                 0.196 
                 0.268 
                 0.179 
                 0.222 
                 0.234 
                 0.172 
               
               
                 Sens 2 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
                 80% 
                 81% 
                 80% 
                 81% 
               
               
                 Spec 2 
                 31% 
                 35% 
                 29% 
                 23% 
                 31% 
                 20% 
                 28% 
                 25% 
                 18% 
               
               
                 Cutoff 3 
                 0.146 
                 0.163 
                 0.151 
                 0.143 
                 0.199 
                 0.119 
                 0.104 
                 0.168 
                 0.0781 
               
               
                 Sens 3 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 91% 
                 91% 
                 91% 
               
               
                 Spec 3 
                 15% 
                 15% 
                 15% 
                 15% 
                 20% 
                 11% 
                 9% 
                 16% 
                 6% 
               
               
                 Cutoff 4 
                 0.592 
                 0.668 
                 0.648 
                 0.592 
                 0.668 
                 0.648 
                 0.592 
                 0.668 
                 0.648 
               
               
                 Sens 4 
                 41% 
                 51% 
                 37% 
                 29% 
                 38% 
                 31% 
                 34% 
                 36% 
                 29% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 0.869 
                 0.983 
                 0.977 
                 0.869 
                 0.983 
                 0.977 
                 0.869 
                 0.983 
                 0.977 
               
               
                 Sens 5 
                 31% 
                 40% 
                 28% 
                 18% 
                 32% 
                 16% 
                 22% 
                 27% 
                 23% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 1.32 
                 1.60 
                 1.97 
                 1.32 
                 1.60 
                 1.97 
                 1.32 
                 1.60 
                 1.97 
               
               
                 Sens 6 
                 21% 
                 31% 
                 15% 
                 10% 
                 20% 
                 7% 
                 16% 
                 22% 
                 16% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 1.5 
                 1.4 
                 1.5 
                 1.1 
                 1.3 
                 1.1 
                 1.5 
                 0.59 
                 1.6 
               
               
                 p Value 
                 0.055 
                 0.39 
                 0.048 
                 0.60 
                 0.56 
                 0.80 
                 0.27 
                 0.32 
                 0.17 
               
               
                 95% CI of 
                 0.99 
                 0.68 
                 1.0 
                 0.69 
                 0.58 
                 0.64 
                 0.72 
                 0.21 
                 0.81 
               
               
                 OR Quart2 
                 2.3 
                 2.7 
                 2.3 
                 1.9 
                 2.7 
                 1.8 
                 3.2 
                 1.6 
                 3.3 
               
               
                 OR Quart 3 
                 1.7 
                 1.6 
                 1.4 
                 1.1 
                 1.8 
                 1.1 
                 1.5 
                 1.5 
                 1.2 
               
               
                 p Value 
                 0.015 
                 0.18 
                 0.16 
                 0.79 
                 0.11 
                 0.70 
                 0.27 
                 0.31 
                 0.70 
               
               
                 95% CI of 
                 1.1 
                 0.81 
                 0.89 
                 0.64 
                 0.87 
                 0.67 
                 0.72 
                 0.67 
                 0.55 
               
               
                 OR Quart3 
                 2.6 
                 3.1 
                 2.1 
                 1.8 
                 3.7 
                 1.8 
                 3.2 
                 3.5 
                 2.4 
               
               
                 OR Quart 4 
                 2.5 
                 3.8 
                 1.9 
                 1.2 
                 2.3 
                 1.1 
                 1.2 
                 1.4 
                 1.2 
               
               
                 p Value 
                 2.0E−5 
                 1.0E−5 
                 0.0032 
                 0.44 
                 0.023 
                 0.80 
                 0.57 
                 0.41 
                 0.58 
               
               
                 95% CI of 
                 1.6 
                 2.1 
                 1.2 
                 0.74 
                 1.1 
                 0.64 
                 0.58 
                 0.62 
                 0.59 
               
               
                 OR Quart4 
                 3.8 
                 7.0 
                 2.8 
                 2.0 
                 4.6 
                 1.8 
                 2.7 
                 3.2 
                 2.6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.2 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0 or R) and in urine samples collected from subjects at  
               
               
                 0, 24 hours, and 48 hours prior to reaching stage I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 C-C motif chemokine 14 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.397 
                 0.741 
                 0.397 
                 0.475 
                 0.397 
                 0.374 
               
               
                 Average 
                 0.777 
                 1.57 
                 0.777 
                 1.04 
                 0.777 
                 1.03 
               
               
                 Stdev 
                 1.22 
                 1.99 
                 1.22 
                 1.60 
                 1.22 
                 1.76 
               
               
                 p(t-test) 
                   
                 1.4E−12 
                   
                 0.026 
                   
                 0.098 
               
               
                 Min 
                 2.08E−6 
                 0.0110 
                 2.08E−6 
                 0.0184 
                 2.08E−6 
                 0.00229 
               
               
                 Max 
                 10.4 
                 9.06 
                 10.4 
                 9.26 
                 10.4 
                 9.39 
               
               
                 n (Samp) 
                 970 
                 183 
                 970 
                 133 
                 970 
                 76 
               
               
                 n (Patient) 
                 249 
                 183 
                 249 
                 133 
                 249 
                 76 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.441 
                 1.19 
                 0.441 
                 0.673 
                 0.441 
                 0.565 
               
               
                 Average 
                 0.837 
                 2.39 
                 0.837 
                 1.94 
                 0.837 
                 1.51 
               
               
                 Stdev 
                 1.22 
                 2.49 
                 1.22 
                 2.48 
                 1.22 
                 2.26 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 p(t-test) 
                   
                 5.3E−19 
                   
                 3.9E−9 
                   
                 0.0019 
               
               
                 Min 
                 2.08E−6 
                 0.000562 
                 2.08E−6 
                 0.0926 
                 2.08E−6 
                 0.0516 
               
               
                 Max 
                 10.4 
                 8.81 
                 10.4 
                 9.07 
                 10.4 
                 9.06 
               
               
                 n (Samp) 
                 1464 
                 59 
                 1464 
                 49 
                 1464 
                 34 
               
               
                 n (Patient) 
                 380 
                 59 
                 380 
                 49 
                 380 
                 34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.428 
                 0.657 
                 0.428 
                 0.464 
                 0.428 
                 0.411 
               
               
                 Average 
                 0.992 
                 1.38 
                 0.992 
                 1.01 
                 0.992 
                 1.00 
               
               
                 Stdev 
                 1.59 
                 1.78 
                 1.59 
                 1.51 
                 1.59 
                 1.69 
               
               
                 p(t-test) 
                   
                 0.0057 
                   
                 0.91 
                   
                 0.96 
               
               
                 Min 
                 2.08E−6 
                 0.0110 
                 2.08E−6 
                 0.0184 
                 2.08E−6 
                 0.00229 
               
               
                 Max 
                 10.4 
                 9.06 
                 10.4 
                 9.26 
                 10.4 
                 9.39 
               
               
                 n (Samp) 
                 1113 
                 156 
                 1113 
                 118 
                 1113 
                 67 
               
               
                 n (Patient) 
                 274 
                 156 
                 274 
                 118 
                 274 
                 67 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.67 
                 0.73 
                 0.62 
                 0.55 
                 0.69 
                 0.52 
                 0.50 
                 0.58 
                 0.49 
               
               
                 SE 
                 0.023 
                 0.038 
                 0.025 
                 0.027 
                 0.043 
                 0.028 
                 0.034 
                 0.052 
                 0.037 
               
               
                 P 
                 2.6E−13 
                 7.5E−10 
                 1.8E−6 
                 0.062 
                 1.4E−5 
                 0.52 
                 0.92 
                 0.13 
                 0.72 
               
               
                 nCohort 1 
                 970 
                 1464 
                 1113 
                 970 
                 1464 
                 1113 
                 970 
                 1464 
                 1113 
               
               
                 nCohort 2 
                 183 
                 59 
                 156 
                 133 
                 49 
                 118 
                 76 
                 34 
                 67 
               
               
                 Cutoff 1 
                 0.434 
                 0.512 
                 0.415 
                 0.280 
                 0.558 
                 0.280 
                 0.251 
                 0.372 
                 0.275 
               
               
                 Sens 1 
                 70% 
                 71% 
                 71% 
                 71% 
                 71% 
                 70% 
                 71% 
                 71% 
                 70% 
               
               
                 Spec 1 
                 54% 
                 57% 
                 49% 
                 36% 
                 61% 
                 33% 
                 30% 
                 43% 
                 32% 
               
               
                 Cutoff 2 
                 0.326 
                 0.386 
                 0.315 
                 0.219 
                 0.401 
                 0.216 
                 0.196 
                 0.253 
                 0.211 
               
               
                 Sens 2 
                 80% 
                 81% 
                 80% 
                 80% 
                 82% 
                 81% 
                 80% 
                 82% 
                 81% 
               
               
                 Spec 2 
                 41% 
                 45% 
                 37% 
                 25% 
                 46% 
                 22% 
                 22% 
                 27% 
                 21% 
               
               
                 Cutoff 3 
                 0.230 
                 0.307 
                 0.216 
                 0.140 
                 0.220 
                 0.134 
                 0.170 
                 0.185 
                 0.170 
               
               
                 Sens 3 
                 90% 
                 92% 
                 90% 
                 90% 
                 92% 
                 91% 
                 91% 
                 91% 
                 91% 
               
               
                 Spec 3 
                 26% 
                 35% 
                 22% 
                 13% 
                 21% 
                 11% 
                 18% 
                 17% 
                 16% 
               
               
                 Cutoff 4 
                 0.639 
                 0.742 
                 0.754 
                 0.639 
                 0.742 
                 0.754 
                 0.639 
                 0.742 
                 0.754 
               
               
                 Sens 4 
                 54% 
                 66% 
                 46% 
                 34% 
                 47% 
                 33% 
                 29% 
                 38% 
                 25% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 0.927 
                 1.08 
                 1.13 
                 0.927 
                 1.08 
                 1.13 
                 0.927 
                 1.08 
                 1.13 
               
               
                 Sens 5 
                 41% 
                 54% 
                 35% 
                 25% 
                 41% 
                 21% 
                 22% 
                 26% 
                 21% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 1.59 
                 1.82 
                 2.64 
                 1.59 
                 1.82 
                 2.64 
                 1.59 
                 1.82 
                 2.64 
               
               
                 Sens 6 
                 27% 
                 41% 
                 16% 
                 18% 
                 27% 
                  9% 
                 16% 
                 21% 
                  9% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 1.6 
                 2.8 
                 1.2 
                 1.00 
                 1.4 
                 1.1 
                 1.3 
                 2.0 
                 0.93 
               
               
                 p Value 
                 0.089 
                 0.081 
                 0.47 
                 0.99 
                 0.56 
                 0.69 
                 0.42 
                 0.20 
                 0.85 
               
               
                 95% CI of 
                 0.93 
                 0.88 
                 0.70 
                 0.58 
                 0.44 
                 0.65 
                 0.68 
                 0.68 
                 0.45 
               
               
                 OR Quart2 
                 2.9 
                 8.9 
                 2.2 
                 1.7 
                 4.5 
                 1.9 
                 2.5 
                 6.0 
                 1.9 
               
               
                 OR Quart 3 
                 2.6 
                 2.0 
                 2.2 
                 1.3 
                 2.9 
                 1.0 
                 0.88 
                 1.6 
                 1.3 
               
               
                 p Value 
                 5.1E−4 
                 0.26 
                 0.0040 
                 0.30 
                 0.045 
                 0.90 
                 0.72 
                 0.41 
                 0.49 
               
               
                 95% CI of 
                 1.5 
                 0.60 
                 1.3 
                 0.78 
                 1.0 
                 0.60 
                 0.44 
                 0.52 
                 0.64 
               
               
                 OR Quart3 
                 4.5 
                 6.8 
                 3.7 
                 2.2 
                 8.0 
                 1.8 
                 1.8 
                 5.0 
                 2.5 
               
               
                 OR Quart 4 
                 4.9 
                 9.8 
                 2.9 
                 1.4 
                 4.8 
                 1.2 
                 1.1 
                 2.2 
                 1.0 
               
               
                 p Value 
                 1.5E−9 
                 1.8E−5 
                 4.0E−5 
                 0.25 
                 0.0016 
                 0.42 
                 0.87 
                 0.14 
                 1.0 
               
               
                 95% CI of 
                 2.9 
                 3.5 
                 1.7 
                 0.81 
                 1.8 
                 0.73 
                 0.54 
                 0.77 
                 0.49 
               
               
                 OR Quart4 
                 8.1 
                 28 
                 4.8 
                 2.3 
                 13 
                 2.1 
                 2.1 
                 6.5 
                 2.0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.3 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected within 12 hours of 
               
               
                 reaching stage R from Cohort 1 (patients that reached, but did not progress beyond, 
               
               
                 RIFLE stage R) and from Cohort 2 (patients that reached RIFLE stage I or F). 
               
               
                   
               
             
            
               
                 C-C motif chemokine 14 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.462 
                 0.657 
                 0.795 
                 1.45 
                 0.461 
                 0.664 
               
               
                 Average 
                 0.689 
                 1.43 
                 0.801 
                 2.27 
                 0.890 
                 1.42 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Stdev 
                 0.724 
                 1.84 
                 0.595 
                 2.38 
                 1.33 
                 1.82 
               
               
                 p(t-test) 
                   
                 0.0085 
                   
                 0.0064 
                   
                 0.066 
               
               
                 Min 
                 2.08E−6 
                 0.0157 
                 2.08E−6 
                 0.110 
                 0.0313 
                 0.0157 
               
               
                 Max 
                 3.38 
                 8.57 
                 2.51 
                 8.78 
                 7.84 
                 8.08 
               
               
                 n (Samp) 
                 46 
                 126 
                 22 
                 38 
                 49 
                 115 
               
               
                 n (Patient) 
                 46 
                 126 
                 22 
                 38 
                 49 
                 115 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.63 
                 0.69 
                 0.61 
               
               
                 SE 
                 0.046 
                 0.068 
                 0.046 
               
               
                 P 
                 0.0046 
                 0.0042 
                 0.017 
               
               
                 nCohort 1 
                 46 
                 22 
                 49 
               
               
                 nCohort 2 
                 126 
                 38 
                 115 
               
               
                 Cutoff 1 
                 0.384 
                 0.518 
                 0.370 
               
               
                 Sens 1 
                 71% 
                 71% 
                 70% 
               
               
                 Spec 1 
                 43% 
                 32% 
                 39% 
               
               
                 Cutoff 2 
                 0.309 
                 0.435 
                 0.291 
               
               
                 Sens 2 
                 80% 
                 82% 
                 80% 
               
               
                 Spec 2 
                 35% 
                 32% 
                 33% 
               
               
                 Cutoff 3 
                 0.224 
                 0.302 
                 0.214 
               
               
                 Sens 3 
                 90% 
                 92% 
                 90% 
               
               
                 Spec 3 
                 22% 
                 27% 
                 20% 
               
               
                 Cutoff 4 
                 0.754 
                 0.977 
                 0.708 
               
               
                 Sens 4 
                 45% 
                 61% 
                 49% 
               
               
                 Spec 4 
                 72% 
                 73% 
                 71% 
               
               
                 Cutoff 5 
                 0.977 
                 1.10 
                 1.09 
               
               
                 Sens 5 
                 38% 
                 58% 
                 35% 
               
               
                 Spec 5 
                 80% 
                 82% 
                 82% 
               
               
                 Cutoff 6 
                 1.42 
                 1.42 
                 2.81 
               
               
                 Sens 6 
                 27% 
                 50% 
                 16% 
               
               
                 Spec 6 
                 91% 
                 91% 
                 92% 
               
               
                 OR Quart 2 
                 1.7 
                 0.77 
                 1.1 
               
               
                 p Value 
                 0.25 
                 0.72 
                 0.82 
               
               
                 95% CI of 
                 0.69 
                 0.18 
                 0.45 
               
               
                 OR Quart2 
                 4.3 
                 3.2 
                 2.7 
               
               
                 OR Quart 3 
                 1.2 
                 1.3 
                 2.0 
               
               
                 p Value 
                 0.65 
                 0.71 
                 0.16 
               
               
                 95% CI of 
                 0.50 
                 0.31 
                 0.77 
               
               
                 OR Quart3 
                 3.0 
                 5.6 
                 5.1 
               
               
                 OR Quart 4 
                 4.5 
                 12 
                 2.6 
               
               
                 p Value 
                 0.0084 
                 0.030 
                 0.056 
               
               
                 95% CI of 
                 1.5 
                 1.3 
                 0.98 
               
               
                 OR Quart4 
                 14 
                 120 
                 7.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.4 
               
               
                   
               
               
                 Comparison of the maximum marker levels in urine samples collected from 
               
               
                 Cohort 1 (patients that did not progress beyond RIFLE stage 0) and the maximum values 
               
               
                 in urine samples collected from subjects between enrollment and 0, 24 hours, and 48 
               
               
                 hours prior to reaching stage F in Cohort 2. 
               
               
                   
               
             
            
               
                 C-C motif chemokine 14 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.616 
                 3.05 
                 0.616 
                 1.84 
                 0.616 
                 0.853 
               
               
                 Average 
                 1.09 
                 3.78 
                 1.09 
                 3.30 
                 1.09 
                 2.63 
               
               
                 Stdev 
                 1.41 
                 2.90 
                 1.41 
                 2.99 
                 1.41 
                 3.10 
               
               
                 p(t-test) 
                   
                 1.7E−14 
                   
                 8.0E−10 
                   
                 1.5E−4 
               
               
                 Min 
                 0.0409 
                 0.110 
                 0.0409 
                 0.110 
                 0.0409 
                 0.185 
               
               
                 Max 
                 8.80 
                 9.39 
                 8.80 
                 9.39 
                 8.80 
                 9.39 
               
               
                 n (Samp) 
                 137 
                 47 
                 137 
                 39 
                 137 
                 23 
               
               
                 n (Patient) 
                 137 
                 47 
                 137 
                 39 
                 137 
                 23 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.670 
                 4.44 
                 0.670 
                 2.70 
                 0.670 
                 1.35 
               
               
                 Average 
                 1.21 
                 4.51 
                 1.21 
                 4.06 
                 1.21 
                 3.05 
               
               
                 Stdev 
                 1.43 
                 3.20 
                 1.43 
                 3.21 
                 1.43 
                 3.35 
               
               
                 p(t-test) 
                   
                 1.8E−21 
                   
                 7.8E−16 
                   
                 2.6E−6 
               
               
                 Min 
                 0.0409 
                 0.284 
                 0.0409 
                 0.240 
                 0.0409 
                 0.185 
               
               
                 Max 
                 8.80 
                 9.39 
                 8.80 
                 9.39 
                 8.80 
                 9.39 
               
               
                 n (Samp) 
                 315 
                 28 
                 315 
                 25 
                 315 
                 18 
               
               
                 n (Patient) 
                 315 
                 28 
                 315 
                 25 
                 315 
                 18 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.619 
                 2.57 
                 0.619 
                 1.67 
                 0.619 
                 0.686 
               
               
                 Average 
                 1.32 
                 3.21 
                 1.32 
                 2.75 
                 1.32 
                 1.79 
               
               
                 Stdev 
                 1.84 
                 2.50 
                 1.84 
                 2.71 
                 1.84 
                 2.17 
               
               
                 p(t-test) 
                   
                 1.2E−6 
                   
                 5.8E−4 
                   
                 0.37 
               
               
                 Min 
                 0.000797 
                 0.110 
                 0.000797 
                 0.110 
                 0.000797 
                 0.221 
               
               
                 Max 
                 10.4 
                 8.88 
                 10.4 
                 8.88 
                 10.4 
                 6.68 
               
               
                 n (Samp) 
                 172 
                 32 
                 172 
                 27 
                 172 
                 14 
               
               
                 n (Patient) 
                 172 
                 32 
                 172 
                 27 
                 172 
                 14 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.82 
                 0.82 
                 0.77 
                 0.77 
                 0.79 
                 0.70 
                 0.62 
                 0.61 
                 0.57 
               
               
                 SE 
                 0.040 
                 0.050 
                 0.051 
                 0.047 
                 0.055 
                 0.059 
                 0.066 
                 0.072 
                 0.083 
               
               
                 P 
                 2.4E−15 
                 1.3E−10 
                 1.1E−7 
                 1.9E−8 
                 7.9E−8 
                 9.4E−4 
                 0.067 
                 0.13 
                 0.42 
               
               
                 nCohort 1 
                 137 
                 315 
                 172 
                 137 
                 315 
                 172 
                 137 
                 315 
                 172 
               
               
                 nCohort 2 
                 47 
                 28 
                 32 
                 39 
                 25 
                 27 
                 23 
                 18 
                 14 
               
               
                 Cutoff 1 
                 1.79 
                 1.92 
                 1.33 
                 0.937 
                 1.66 
                 0.677 
                 0.606 
                 0.590 
                 0.606 
               
               
                 Sens 1 
                 70% 
                 71% 
                 72% 
                 72% 
                 72% 
                 70% 
                 74% 
                 72% 
                 71% 
               
               
                 Spec 1 
                 87% 
                 85% 
                 77% 
                 69% 
                 81% 
                 55% 
                 50% 
                 44% 
                 49% 
               
               
                 Cutoff 2 
                 0.891 
                 0.851 
                 0.891 
                 0.590 
                 0.851 
                 0.556 
                 0.350 
                 0.350 
                 0.352 
               
               
                 Sens 2 
                 81% 
                 82% 
                 81% 
                 82% 
                 80% 
                 81% 
                 83% 
                 83% 
                 86% 
               
               
                 Spec 2 
                 66% 
                 59% 
                 62% 
                 49% 
                 59% 
                 44% 
                 21% 
                 19% 
                 20% 
               
               
                 Cutoff 3 
                 0.495 
                 0.502 
                 0.456 
                 0.495 
                 0.506 
                 0.398 
                 0.216 
                 0.211 
                 0.270 
               
               
                 Sens 3 
                 91% 
                 93% 
                 91% 
                 92% 
                 92% 
                 93% 
                 91% 
                 94% 
                 93% 
               
               
                 Spec 3 
                 39% 
                 35% 
                 34% 
                 39% 
                 35% 
                 27% 
                 9% 
                 6% 
                 14% 
               
               
                 Cutoff 4 
                 0.971 
                 1.20 
                 1.13 
                 0.971 
                 1.20 
                 1.13 
                 0.971 
                 1.20 
                 1.13 
               
               
                 Sens 4 
                 77% 
                 79% 
                 72% 
                 69% 
                 72% 
                 59% 
                 43% 
                 50% 
                 36% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 1.38 
                 1.62 
                 1.58 
                 1.38 
                 1.62 
                 1.58 
                 1.38 
                 1.62 
                 1.58 
               
               
                 Sens 5 
                 72% 
                 79% 
                 69% 
                 62% 
                 72% 
                 52% 
                 43% 
                 50% 
                 36% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 2.31 
                 2.86 
                 3.08 
                 2.31 
                 2.86 
                 3.08 
                 2.31 
                 2.86 
                 3.08 
               
               
                 Sens 6 
                 60% 
                 54% 
                 44% 
                 44% 
                 44% 
                 33% 
                 30% 
                 33% 
                 21% 
               
               
                 Spec 6 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 1.7 
                 1.5 
                 1.0 
                 2.2 
                 4.1 
                 3.2 
                 0.30 
                 0.59 
                 0.98 
               
               
                 p Value 
                 0.46 
                 0.66 
                 1.0 
                 0.30 
                 0.21 
                 0.17 
                 0.15 
                 0.47 
                 0.98 
               
               
                 95% CI of 
                 0.39 
                 0.24 
                 0.19 
                 0.50 
                 0.45 
                 0.61 
                 0.056 
                 0.14 
                 0.19 
               
               
                 OR Quart2 
                 7.8 
                 9.2 
                 5.2 
                 9.2 
                 38 
                 17 
                 1.6 
                 2.5 
                 5.1 
               
               
                 OR Quart 3 
                 3.5 
                 0.49 
                 1.7 
                 2.6 
                 2.0 
                 2.0 
                 0.81 
                 0.19 
                 1.0 
               
               
                 p Value 
                 0.076 
                 0.56 
                 0.47 
                 0.19 
                 0.57 
                 0.42 
                 0.75 
                 0.13 
                 1.0 
               
               
                 95% CI of 
                 0.88 
                 0.043 
                 0.39 
                 0.62 
                 0.18 
                 0.36 
                 0.23 
                 0.022 
                 0.19 
               
               
                 OR Quart3 
                 14 
                 5.5 
                 7.7 
                 11 
                 23 
                 12 
                 2.9 
                 1.7 
                 5.2 
               
               
                 OR Quart 4 
                 27 
                 14 
                 11 
                 15 
                 23 
                 10 
                 1.9 
                 1.9 
                 1.7 
               
               
                 p Value 
                 9.9E−7 
                 4.5E−4 
                 2.5E−4 
                 5.4E−5 
                 0.0027 
                 0.0033 
                 0.27 
                 0.28 
                 0.48 
               
               
                 95% CI of 
                 7.2 
                 3.2 
                 3.1 
                 4.0 
                 2.9 
                 2.2 
                 0.61 
                 0.60 
                 0.38 
               
               
                 OR Quart4 
                 100 
                 63 
                 41 
                 56 
                 170 
                 47 
                 5.8 
                 5.8 
                 7.6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.5 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0) and in urine samples collected from 
               
               
                 subjects at 0, 24 hours, and 48 hours prior to reaching stage R, I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 C-C motif chemokine 16 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 8.17E−6 
                 0.000221 
                 8.17E−6 
                 9.29E−6 
                 8.17E−6 
                 7.11E−6 
               
               
                 Average 
                 0.00491 
                 0.0120 
                 0.00491 
                 0.00833 
                 0.00491 
                 0.0161 
               
               
                 Stdev 
                 0.0138 
                 0.0577 
                 0.0138 
                 0.0354 
                 0.0138 
                 0.0894 
               
               
                 p(t-test) 
                   
                 0.0071 
                   
                 0.073 
                   
                 0.0082 
               
               
                 Min 
                 2.10E−6 
                 1.99E−6 
                 2.10E−6 
                 2.10E−6 
                 2.10E−6 
                 2.10E−6 
               
               
                 Max 
                 0.158 
                 0.692 
                 0.158 
                 0.372 
                 0.158 
                 0.718 
               
               
                 n (Samp) 
                 528 
                 287 
                 528 
                 152 
                 528 
                 67 
               
               
                 n (Patient) 
                 137 
                 287 
                 137 
                 152 
                 137 
                 67 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 8.61E−6 
                 0.00158 
                 8.61E−6 
                 1.41E−5 
                 8.61E−6 
                 8.17E−6 
               
               
                 Average 
                 0.00464 
                 0.0263 
                 0.00464 
                 0.0143 
                 0.00464 
                 0.0311 
               
               
                 Stdev 
                 0.0130 
                 0.0954 
                 0.0130 
                 0.0315 
                 0.0130 
                 0.115 
               
               
                 p(t-test) 
                   
                 1.3E−12 
                   
                 5.7E−8 
                   
                 7.3E−12 
               
               
                 Min 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 2.10E−6 
                 1.99E−6 
                 2.10E−6 
               
               
                 Max 
                 0.187 
                 0.692 
                 0.187 
                 0.156 
                 0.187 
                 0.718 
               
               
                 n (Samp) 
                 1187 
                 109 
                 1187 
                 74 
                 1187 
                 45 
               
               
                 n (Patient) 
                 315 
                 109 
                 315 
                 74 
                 315 
                 45 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 8.52E−6 
                 0.000224 
                 8.52E−6 
                 9.29E−6 
                 8.52E−6 
                 7.11E−6 
               
               
                 Average 
                 0.0100 
                 0.0260 
                 0.0100 
                 0.0602 
                 0.0100 
                 0.0843 
               
               
                 Stdev 
                 0.0547 
                 0.286 
                 0.0547 
                 0.631 
                 0.0547 
                 0.501 
               
               
                 p(t-test) 
                   
                 0.16 
                   
                 0.041 
                   
                 2.4E−4 
               
               
                 Min 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 2.10E−6 
               
               
                 Max 
                 0.819 
                 4.61 
                 0.819 
                 7.64 
                 0.819 
                 4.05 
               
               
                 n (Samp) 
                 685 
                 261 
                 685 
                 147 
                 685 
                 69 
               
               
                 n (Patient) 
                 172 
                 261 
                 172 
                 147 
                 172 
                 69 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.58 
                 0.61 
                 0.57 
                 0.51 
                 0.58 
                 0.50 
                 0.45 
                 0.52 
                 0.47 
               
               
                 SE 
                 0.021 
                 0.030 
                 0.021 
                 0.027 
                 0.036 
                 0.026 
                 0.038 
                 0.044 
                 0.037 
               
               
                 P 
                 4.0E−4 
                 3.9E−4 
                 0.0018 
                 0.61 
                 0.017 
                 0.95 
                 0.20 
                 0.72 
                 0.45 
               
               
                 nCohort 1 
                 528 
                 1187 
                 685 
                 528 
                 1187 
                 685 
                 528 
                 1187 
                 685 
               
               
                 nCohort 2 
                 287 
                 109 
                 261 
                 152 
                 74 
                 147 
                 67 
                 45 
                 69 
               
               
                 Cutoff 1 
                 7.11E−6 
                 7.11E−6 
                 7.11E−6 
                 5.32E−6 
                 7.11E−6 
                 5.28E−6 
                 4.12E−6 
                 5.28E−6 
                 4.50E−6 
               
               
                 Sens 1 
                 70% 
                 72% 
                 70% 
                 71% 
                 72% 
                 73% 
                 72% 
                 71% 
                 72% 
               
               
                 Spec 1 
                 42% 
                 39% 
                 40% 
                 34% 
                 39% 
                 29% 
                 22% 
                 28% 
                 24% 
               
               
                 Cutoff 2 
                 4.27E−6 
                 4.98E−6 
                 4.27E−6 
                 3.90E−6 
                 4.98E−6 
                 3.90E−6 
                 3.61E−6 
                 3.61E−6 
                 3.90E−6 
               
               
                 Sens 2 
                 81% 
                 81% 
                 80% 
                 83% 
                 81% 
                 81% 
                 81% 
                 80% 
                 83% 
               
               
                 Spec 2 
                 22% 
                 25% 
                 22% 
                 19% 
                 25% 
                 19% 
                 16% 
                 16% 
                 19% 
               
               
                 Cutoff 3 
                 2.97E−6 
                 3.45E−6 
                 2.97E−6 
                 2.55E−6 
                 3.59E−6 
                 2.35E−6 
                 2.35E−6 
                 2.55E−6 
                 2.55E−6 
               
               
                 Sens 3 
                 91% 
                 91% 
                 91% 
                 91% 
                 92% 
                 93% 
                 93% 
                 93% 
                 91% 
               
               
                 Spec 3 
                 12% 
                 13% 
                 12% 
                  9% 
                 13% 
                  5% 
                  6% 
                  9% 
                  9% 
               
               
                 Cutoff 4 
                 0.000773 
                 0.00151 
                 0.00176 
                 0.000773 
                 0.00151 
                 0.00176 
                 0.000773 
                 0.00151 
                 0.00176 
               
               
                 Sens 4 
                 43% 
                 50% 
                 40% 
                 33% 
                 41% 
                 33% 
                 25% 
                 33% 
                 28% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 0.00616 
                 0.00593 
                 0.00690 
                 0.00616 
                 0.00593 
                 0.00690 
                 0.00616 
                 0.00593 
                 0.00690 
               
               
                 Sens 5 
                 25% 
                 34% 
                 26% 
                 18% 
                 27% 
                 20% 
                 16% 
                 29% 
                 20% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 0.0149 
                 0.0144 
                 0.0169 
                 0.0149 
                 0.0144 
                 0.0169 
                 0.0149 
                 0.0144 
                 0.0169 
               
               
                 Sens 6 
                 16% 
                 23% 
                 16% 
                  9% 
                 20% 
                  8% 
                 10% 
                 20% 
                  9% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 1.0 
                 0.90 
                 0.90 
                 1.1 
                 1.1 
                 0.97 
                 0.84 
                 1.1 
                 0.94 
               
               
                 p Value 
                 0.85 
                 0.74 
                 0.65 
                 0.69 
                 0.85 
                 0.90 
                 0.68 
                 0.83 
                 0.86 
               
               
                 95% CI of 
                 0.68 
                 0.47 
                 0.59 
                 0.66 
                 0.51 
                 0.58 
                 0.38 
                 0.48 
                 0.45 
               
               
                 OR Quart2 
                 1.6 
                 1.7 
                 1.4 
                 1.9 
                 2.3 
                 1.6 
                 1.9 
                 2.5 
                 2.0 
               
               
                 OR Quart 3 
                 1.5 
                 1.3 
                 1.4 
                 1.2 
                 1.5 
                 1.1 
                 1.4 
                 0.63 
                 1.2 
               
               
                 p Value 
                 0.065 
                 0.45 
                 0.100 
                 0.51 
                 0.29 
                 0.61 
                 0.36 
                 0.34 
                 0.59 
               
               
                 95% CI of 
                 0.98 
                 0.69 
                 0.94 
                 0.71 
                 0.72 
                 0.69 
                 0.68 
                 0.24 
                 0.60 
               
               
                 OR Quart3 
                 2.2 
                 2.3 
                 2.1 
                 2.0 
                 2.9 
                 1.9 
                 2.9 
                 1.6 
                 2.4 
               
               
                 OR Quart 4 
                 1.8 
                 2.2 
                 1.5 
                 1.1 
                 1.8 
                 1.0 
                 1.7 
                 1.4 
                 1.2 
               
               
                 p Value 
                 0.0062 
                 0.0045 
                 0.035 
                 0.60 
                 0.074 
                 1.0 
                 0.15 
                 0.42 
                 0.58 
               
               
                 95% CI of 
                 1.2 
                 1.3 
                 1.0 
                 0.69 
                 0.94 
                 0.60 
                 0.83 
                 0.62 
                 0.60 
               
               
                 OR Quart4 
                 2.7 
                 3.8 
                 2.3 
                 1.9 
                 3.6 
                 1.7 
                 3.4 
                 3.1 
                 2.4 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.6 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0 or R) and in urine samples collected from subjects at 0, 24 hours, 
               
               
                 and 48 hours prior to reaching stage I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 C-C motif chemokine 16 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 8.17E−6 
                 0.000773 
                 8.17E−6 
                 1.41E−5 
                 8.17E−6 
                 1.31E−5 
               
               
                 Average 
                 0.00545 
                 0.0233 
                 0.00545 
                 0.0173 
                 0.00545 
                 0.0149 
               
               
                 Stdev 
                 0.0252 
                 0.0828 
                 0.0252 
                 0.0629 
                 0.0252 
                 0.0828 
               
               
                 p(t-test) 
                   
                 4.3E−8 
                   
                 6.5E−5 
                   
                 0.016 
               
               
                 Min 
                 2.10E−6 
                 1.99E−6 
                 2.10E−6 
                 2.10E−6 
                 2.10E−6 
                 2.10E−6 
               
               
                 Max 
                 0.649 
                 0.692 
                 0.649 
                 0.568 
                 0.649 
                 0.718 
               
               
                 n (Samp) 
                 971 
                 183 
                 971 
                 133 
                 971 
                 76 
               
               
                 n (Patient) 
                 249 
                 183 
                 249 
                 133 
                 249 
                 76 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 8.61E−6 
                 0.00462 
                 8.61E−6 
                 0.00430 
                 8.61E−6 
                 0.00293 
               
               
                 Average 
                 0.00567 
                 0.0566 
                 0.00567 
                 0.0292 
                 0.00567 
                 0.0157 
               
               
                 Stdev 
                 0.0227 
                 0.137 
                 0.0227 
                 0.0838 
                 0.0227 
                 0.0483 
               
               
                 p(t-test) 
                   
                 2.9E−27 
                   
                 2.0E−9 
                   
                 0.014 
               
               
                 Min 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 2.10E−6 
               
               
                 Max 
                 0.649 
                 0.692 
                 0.649 
                 0.568 
                 0.649 
                 0.278 
               
               
                 n (Samp) 
                 1465 
                 59 
                 1465 
                 49 
                 1465 
                 34 
               
               
                 n (Patient) 
                 380 
                 59 
                 380 
                 49 
                 380 
                 34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 8.61E−6 
                 0.000636 
                 8.61E−6 
                 1.36E−5 
                 8.61E−6 
                 1.31E−5 
               
               
                 Average 
                 0.0532 
                 0.0122 
                 0.0532 
                 0.0124 
                 0.0532 
                 0.0179 
               
               
                 Stdev 
                 0.513 
                 0.0322 
                 0.513 
                 0.0418 
                 0.513 
                 0.0913 
               
               
                 p(t-test) 
                   
                 0.32 
                   
                 0.39 
                   
                 0.57 
               
               
                 Min 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 1.99E−6 
                 2.10E−6 
               
               
                 Max 
                 8.98 
                 0.278 
                 8.98 
                 0.372 
                 8.98 
                 0.718 
               
               
                 n (Samp) 
                 1113 
                 156 
                 1113 
                 118 
                 1113 
                 67 
               
               
                 n (Patient) 
                 274 
                 156 
                 274 
                 118 
                 274 
                 67 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.62 
                 0.66 
                 0.60 
                 0.58 
                 0.66 
                 0.54 
                 0.53 
                 0.60 
                 0.51 
               
               
                 SE 
                 0.024 
                 0.039 
                 0.025 
                 0.027 
                 0.043 
                 0.028 
                 0.035 
                 0.052 
                 0.037 
               
               
                 P 
                 1.5E−7 
                 6.8E−5 
                 1.7E−4 
                 0.0024 
                 3.3E−4 
                 0.12 
                 0.37 
                 0.066 
                 0.71 
               
               
                 nCohort 1 
                 971 
                 1465 
                 1113 
                 971 
                 1465 
                 1113 
                 971 
                 1465 
                 1113 
               
               
                 nCohort 2 
                 183 
                 59 
                 156 
                 133 
                 49 
                 118 
                 76 
                 34 
                 67 
               
               
                 Cutoff 1 
                 8.17E−6 
                 8.61E−6 
                 8.17E−6 
                 7.08E−6 
                 8.61E−6 
                 7.08E−6 
                 4.50E−6 
                 6.48E−6 
                 5.28E−6 
               
               
                 Sens 1 
                 71% 
                 73% 
                 71% 
                 71% 
                 73% 
                 70% 
                 72% 
                 71% 
                 72% 
               
               
                 Spec 1 
                 50% 
                 51% 
                 48% 
                 37% 
                 51% 
                 36% 
                 24% 
                 34% 
                 29% 
               
               
                 Cutoff 2 
                 5.28E−6 
                 4.12E−6 
                 5.32E−6 
                 4.27E−6 
                 5.28E−6 
                 4.27E−6 
                 3.90E−6 
                 3.90E−6 
                 3.90E−6 
               
               
                 Sens 2 
                 81% 
                 85% 
                 81% 
                 82% 
                 82% 
                 81% 
                 82% 
                 82% 
                 82% 
               
               
                 Spec 2 
                 30% 
                 20% 
                 32% 
                 22% 
                 27% 
                 22% 
                 19% 
                 18% 
                 19% 
               
               
                 Cutoff 3 
                 3.45E−6 
                 3.45E−6 
                 3.45E−6 
                 2.35E−6 
                 2.35E−6 
                 2.35E−6 
                 2.55E−6 
                 2.55E−6 
                 2.97E−6 
               
               
                 Sens 3 
                 95% 
                 93% 
                 96% 
                 95% 
                 94% 
                 94% 
                 91% 
                 91% 
                 91% 
               
               
                 Spec 3 
                 14% 
                 12% 
                 13% 
                  6% 
                  6% 
                  6% 
                 10% 
                  9% 
                 12% 
               
               
                 Cutoff 4 
                 0.000688 
                 0.00170 
                 0.00215 
                 0.000688 
                 0.00170 
                 0.00215 
                 0.000688 
                 0.00170 
                 0.00215 
               
               
                 Sens 4 
                 51% 
                 59% 
                 42% 
                 43% 
                 55% 
                 37% 
                 39% 
                 59% 
                 31% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 0.00482 
                 0.00610 
                 0.00746 
                 0.00482 
                 0.00610 
                 0.00746 
                 0.00482 
                 0.00610 
                 0.00746 
               
               
                 Sens 5 
                 37% 
                 44% 
                 30% 
                 33% 
                 43% 
                 26% 
                 26% 
                 35% 
                 19% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 0.0142 
                 0.0154 
                 0.0187 
                 0.0142 
                 0.0154 
                 0.0187 
                 0.0142 
                 0.0154 
                 0.0187 
               
               
                 Sens 6 
                 25% 
                 34% 
                 16% 
                 20% 
                 33% 
                 13% 
                  9% 
                 15% 
                  7% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.71 
                 0.33 
                 1.2 
                 0.96 
                 0.62 
                 1.1 
                 0.48 
                 0.49 
                 0.69 
               
               
                 p Value 
                 0.21 
                 0.054 
                 0.49 
                 0.89 
                 0.40 
                 0.79 
                 0.051 
                 0.25 
                 0.34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 95% CI of 
                 0.41 
                 0.10 
                 0.70 
                 0.54 
                 0.20 
                 0.62 
                 0.23 
                 0.15 
                 0.33 
               
               
                 OR Quart2 
                 1.2 
                 1.0 
                 2.1 
                 1.7 
                 1.9 
                 1.9 
                 1.0 
                 1.7 
                 1.5 
               
               
                 OR Quart 3 
                 1.5 
                 0.91 
                 1.7 
                 1.2 
                 1.4 
                 0.91 
                 0.85 
                 0.87 
                 1.2 
               
               
                 p Value 
                 0.077 
                 0.83 
                 0.044 
                 0.58 
                 0.49 
                 0.76 
                 0.62 
                 0.79 
                 0.61 
               
               
                 95% CI of 
                 0.96 
                 0.40 
                 1.0 
                 0.68 
                 0.55 
                 0.51 
                 0.45 
                 0.31 
                 0.61 
               
               
                 OR Quart3 
                 2.5 
                 2.1 
                 2.8 
                 2.0 
                 3.5 
                 1.6 
                 1.6 
                 2.4 
                 2.3 
               
               
                 OR Quart 4 
                 2.6 
                 2.8 
                 2.2 
                 2.0 
                 3.3 
                 1.6 
                 1.1 
                 1.9 
                 1.1 
               
               
                 p Value 
                 2.2E-5 
                 0.0028 
                 0.0017 
                 0.0073 
                 0.0042 
                 0.072 
                 0.77 
                 0.15 
                 0.86 
               
               
                 95% CI of 
                 1.7 
                 1.4 
                 1.3 
                 1.2 
                 1.5 
                 0.96 
                 0.60 
                 0.80 
                 0.54 
               
               
                 OR Quart4 
                 4.1 
                 5.6 
                 3.6 
                 3.3 
                 7.3 
                 2.7 
                 2.0 
                 4.6 
                 2.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.7 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected within 12 hours of 
               
               
                 reaching stage R from Cohort 1 (patients that reached, but did not progress beyond, 
               
               
                 RIFLE stage R) and from Cohort 2 (patients that reached RIFLE stage 1 or F). 
               
               
                   
               
             
            
               
                 C-C motif chemokine 16 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 1.12E−5 
                 0.00172 
                 1.12E−5 
                 0.00400 
                 8.61E−6 
                 0.00209 
               
               
                 Average 
                 0.00367 
                 0.0217 
                 0.00331 
                 0.0527 
                 0.190 
                 0.0113 
               
               
                 Stdev 
                 0.00820 
                 0.0855 
                 0.00546 
                 0.150 
                 1.28 
                 0.0224 
               
               
                 p(t-test) 
                   
                 0.15 
                   
                 0.13 
                   
                 0.14 
               
               
                 Min 
                 2.10E−6 
                 1.99E−6 
                 2.10E−6 
                 1.99E−6 
                 2.10E−6 
                 1.99E−6 
               
               
                 Max 
                 0.0462 
                 0.692 
                 0.0177 
                 0.692 
                 8.98 
                 0.139 
               
               
                 n (Samp) 
                 46 
                 126 
                 22 
                 38 
                 49 
                 115 
               
               
                 n (Patient) 
                 46 
                 126 
                 22 
                 38 
                 49 
                 115 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.61 
                 0.64 
                 0.62 
               
               
                 SE 
                 0.047 
                 0.072 
                 0.046 
               
               
                 P 
                 0.016 
                 0.057 
                 0.0092 
               
               
                 nCohort 1 
                 46 
                 22 
                 49 
               
               
                 nCohort 2 
                 126 
                 38 
                 115 
               
               
                 Cutoff 1 
                 8.52E−6 
                 8.61E−6 
                 8.52E−6 
               
               
                 Sens 1 
                 71% 
                 74% 
                 72% 
               
               
                 Spec 1 
                 46% 
                 45% 
                 45% 
               
               
                 Cutoff 2 
                 5.32E−6 
                 3.61E−6 
                 6.48E−6 
               
               
                 Sens 2 
                 80% 
                 82% 
                 81% 
               
               
                 Spec 2 
                 26% 
                 14% 
                 31% 
               
               
                 Cutoff 3 
                 3.45E−6 
                 2.35E−6 
                 3.45E−6 
               
               
                 Sens 3 
                 92% 
                 92% 
                 93% 
               
               
                 Spec 3 
                 20% 
                  9% 
                 16% 
               
               
                 Cutoff 4 
                 0.00307 
                 0.00307 
                 0.00264 
               
               
                 Sens 4 
                 42% 
                 50% 
                 46% 
               
               
                 Spec 4 
                 72% 
                 73% 
                 71% 
               
               
                 Cutoff 5 
                 0.00473 
                 0.00603 
                 0.00473 
               
               
                 Sens 5 
                 36% 
                 42% 
                 36% 
               
               
                 Spec 5 
                 80% 
                 82% 
                 82% 
               
               
                 Cutoff 6 
                 0.00979 
                 0.0130 
                 0.0232 
               
               
                 Sens 6 
                 27% 
                 32% 
                 14% 
               
               
                 Spec 6 
                 91% 
                 91% 
                 92% 
               
               
                 OR Quart 2 
                 0.65 
                 1.0 
                 0.90 
               
               
                 p Value 
                 0.36 
                 1.0 
                 0.82 
               
               
                 95% CI of 
                 0.26 
                 0.24 
                 0.37 
               
               
                 OR Quart2 
                 1.6 
                 4.2 
                 2.2 
               
               
                 OR Quart 3 
                 1.1 
                 1.8 
                 1.6 
               
               
                 p Value 
                 0.81 
                 0.46 
                 0.34 
               
               
                 95% CI of 
                 0.43 
                 0.40 
                 0.62 
               
               
                 OR Quart3 
                 2.9 
                 7.7 
                 4.0 
               
               
                 OR Quart 4 
                 2.0 
                 3.5 
                 2.8 
               
               
                 p Value 
                 0.20 
                 0.13 
                 0.050 
               
               
                 95% CI of 
                 0.70 
                 0.69 
                 1.00 
               
               
                 OR Quart4 
                 5.7 
                 18 
                 7.9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.8 
               
               
                   
               
               
                 Comparison of the maximum marker levels in urine samples collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0) and the maximum values in urine samples collected from  
               
               
                 subjects between enrollment and 0, 24 hours, and 48 hours prior to reaching stage F in Cohort 2. 
               
               
                   
               
             
            
               
                 C-C motif chemokine 16 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.00380 
                 0.0234 
                 0.00380 
                 0.0177 
                 0.00380 
                 0.0116 
               
               
                 Average 
                 0.0110 
                 0.185 
                 0.0110 
                 0.112 
                 0.0110 
                 0.100 
               
               
                 Stdev 
                 0.0202 
                 0.611 
                 0.0202 
                 0.220 
                 0.0202 
                 0.204 
               
               
                 p(t-test) 
                   
                 9.7E−4 
                   
                 2.8E−7 
                   
                 1.2E−6 
               
               
                 Min 
                 3.61E−6 
                 1.99E−6 
                 3.61E−6 
                 2.10E−6 
                 3.61E−6 
                 5.32E−6 
               
               
                 Max 
                 0.158 
                 4.05 
                 0.158 
                 0.819 
                 0.158 
                 0.718 
               
               
                 n (Samp) 
                 137 
                 47 
                 137 
                 39 
                 137 
                 23 
               
               
                 n (Patient) 
                 137 
                 47 
                 137 
                 39 
                 137 
                 23 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.00380 
                 0.0324 
                 0.00380 
                 0.0235 
                 0.00380 
                 0.0186 
               
               
                 Average 
                 0.0104 
                 0.293 
                 0.0104 
                 0.164 
                 0.0104 
                 0.131 
               
               
                 Stdev 
                 0.0198 
                 0.778 
                 0.0198 
                 0.262 
                 0.0198 
                 0.225 
               
               
                 p(t-test) 
                   
                 2.6E−10 
                   
                 1.5E−21 
                   
                 7.0E−18 
               
               
                 Min 
                 2.35E−6 
                 1.99E−6 
                 2.35E−6 
                 3.61E−6 
                 2.35E−6 
                 5.32E−6 
               
               
                 Max 
                 0.187 
                 4.05 
                 0.187 
                 0.819 
                 0.187 
                 0.718 
               
               
                 n (Samp) 
                 315 
                 28 
                 315 
                 25 
                 315 
                 18 
               
               
                 n (Patient) 
                 315 
                 28 
                 315 
                 25 
                 315 
                 18 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.00373 
                 0.0167 
                 0.00373 
                 0.00910 
                 0.00373 
                 0.00519 
               
               
                 Average 
                 0.0174 
                 0.0349 
                 0.0174 
                 0.0310 
                 0.0174 
                 0.0149 
               
               
                 Stdev 
                 0.0667 
                 0.0446 
                 0.0667 
                 0.0465 
                 0.0667 
                 0.0208 
               
               
                 p(t-test) 
                   
                 0.16 
                   
                 0.31 
                   
                 0.89 
               
               
                 Min 
                 2.10E−6 
                 8.74E−6 
                 2.10E−6 
                 2.10E−6 
                 2.10E−6 
                 7.08E−6 
               
               
                 Max 
                 0.819 
                 0.197 
                 0.819 
                 0.197 
                 0.819 
                 0.0703 
               
               
                 n (Samp) 
                 172 
                 32 
                 172 
                 27 
                 172 
                 14 
               
               
                 n (Patient) 
                 172 
                 32 
                 172 
                 27 
                 172 
                 14 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.74 
                 0.76 
                 0.73 
                 0.72 
                 0.79 
                 0.65 
                 0.67 
                 0.75 
                 0.58 
               
               
                 SE 
                 0.045 
                 0.054 
                 0.053 
                 0.050 
                 0.055 
                 0.061 
                 0.065 
                 0.068 
                 0.083 
               
               
                 P 
                 1.4E−7 
                 1.4E−6 
                 1.9E−5 
                 1.3E−5 
                 1.5E−7 
                 0.011 
                 0.0092 
                 1.7E−4 
                 0.34 
               
               
                 nCohort 1 
                 137 
                 315 
                 172 
                 137 
                 315 
                 172 
                 137 
                 315 
                 172 
               
               
                 nCohort 2 
                 47 
                 28 
                 32 
                 39 
                 25 
                 27 
                 23 
                 18 
                 14 
               
               
                 Cutoff 1 
                 0.00712 
                 0.0100 
                 0.00589 
                 0.00589 
                 0.0100 
                 0.00406 
                 0.00473 
                 0.00746 
                 0.00214 
               
               
                 Sens 1 
                 70% 
                 71% 
                 72% 
                 72% 
                 72% 
                 70% 
                 74% 
                 72% 
                 71% 
               
               
                 Spec 1 
                 57% 
                 69% 
                 56% 
                 54% 
                 69% 
                 52% 
                 53% 
                 59% 
                 42% 
               
               
                 Cutoff 2 
                 0.00422 
                 0.00593 
                 0.00417 
                 0.00260 
                 0.00746 
                 0.00171 
                 0.00214 
                 0.00523 
                 0.000619 
               
               
                 Sens 2 
                 81% 
                 82% 
                 81% 
                 82% 
                 80% 
                 81% 
                 83% 
                 83% 
                 86% 
               
               
                 Spec 2 
                 52% 
                 57% 
                 52% 
                 43% 
                 59% 
                 41% 
                 42% 
                 55% 
                 38% 
               
               
                 Cutoff 3 
                 0.000619 
                 3.59E−6 
                 0.00214 
                 0.000519 
                 0.00260 
                 0.000519 
                 1.36E−5 
                 0.00260 
                 1.36E−5 
               
               
                 Sens 3 
                 91% 
                 93% 
                 91% 
                 92% 
                 92% 
                 93% 
                 91% 
                 94% 
                 93% 
               
               
                 Spec 3 
                 38% 
                  1% 
                 42% 
                 37% 
                 44% 
                 37% 
                 28% 
                 44% 
                 29% 
               
               
                 Cutoff 4 
                 0.0119 
                 0.0115 
                 0.0120 
                 0.0119 
                 0.0115 
                 0.0120 
                 0.0119 
                 0.0115 
                 0.0120 
               
               
                 Sens 4 
                 60% 
                 68% 
                 56% 
                 54% 
                 64% 
                 44% 
                 48% 
                 61% 
                 36% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 0.0167 
                 0.0162 
                 0.0162 
                 0.0167 
                 0.0162 
                 0.0162 
                 0.0167 
                 0.0162 
                 0.0162 
               
               
                 Sens 5 
                 55% 
                 57% 
                 50% 
                 51% 
                 56% 
                 41% 
                 43% 
                 50% 
                 29% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 0.0267 
                 0.0235 
                 0.0282 
                 0.0267 
                 0.0235 
                 0.0282 
                 0.0267 
                 0.0235 
                 0.0282 
               
               
                 Sens 6 
                 43% 
                 50% 
                 34% 
                 41% 
                 48% 
                 30% 
                 30% 
                 44% 
                 14% 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 Spec 6 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 2.9 
                 0.65 
                 9.3 
                 4.0 
                 3.1 
                 3.8 
                 2.7 
                 1.0 
                 5.4 
               
               
                 p Value 
                 0.091 
                 0.64 
                 0.039 
                 0.046 
                 0.34 
                 0.11 
                 0.25 
                 1.0 
                 0.13 
               
               
                 95% CI of 
                 0.84 
                 0.11 
                 1.1 
                 1.0 
                 0.31 
                 0.75 
                 0.49 
                 0.062 
                 0.60 
               
               
                 OR Quart2 
                 10 
                 4.0 
                 77 
                 16 
                 30 
                 19 
                 15 
                 16 
                 48 
               
               
                 OR Quart 3 
                 2.2 
                 2.4 
                 8.0 
                 2.2 
                 6.4 
                 3.2 
                 3.4 
                 6.4 
                 3.1 
               
               
                 p Value 
                 0.22 
                 0.21 
                 0.057 
                 0.30 
                 0.090 
                 0.17 
                 0.15 
                 0.089 
                 0.33 
               
               
                 95% CI of 
                 0.62 
                 0.60 
                 0.94 
                 0.50 
                 0.75 
                 0.61 
                 0.63 
                 0.75 
                 0.31 
               
               
                 OR Quart3 
                 7.9 
                 9.7 
                 67 
                 9.2 
                 54 
                 17 
                 18 
                 54 
                 31 
               
               
                 OR Quart 4 
                 12 
                 6.2 
                 23 
                 11 
                 18 
                 7.4 
                 6.3 
                 11 
                 5.4 
               
               
                 p Value 
                 2.7E−5 
                 0.0048 
                 0.0030 
                 2.8E−4 
                 0.0057 
                 0.012 
                 0.023 
                 0.023 
                 0.13 
               
               
                 95% CI of 
                 3.8 
                 1.7 
                 2.9 
                 3.1 
                 2.3 
                 1.6 
                 1.3 
                 1.4 
                 0.60 
               
               
                 OR Quart4 
                 41 
                 22 
                 180 
                 42 
                 140 
                 35 
                 31 
                 89 
                 48 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.9 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0) and in urine samples collected from subjects at 0, 24 hours, 
               
               
                 and 48 hours prior to reaching stage R, I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 Tyrosine-protein kinase receptor UFO 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 4.93 
                 4.61 
                 4.93 
                 4.08 
                 4.93 
                 3.89 
               
               
                 Average 
                 5.64 
                 5.61 
                 5.64 
                 5.03 
                 5.64 
                 4.88 
               
               
                 Stdev 
                 4.24 
                 4.64 
                 4.24 
                 4.13 
                 4.24 
                 4.05 
               
               
                 p(t-test) 
                   
                 0.93 
                   
                 0.11 
                   
                 0.16 
               
               
                 Min 
                 0.0189 
                 0.00291 
                 0.0189 
                 0.00439 
                 0.0189 
                 0.133 
               
               
                 Max 
                 31.0 
                 28.6 
                 31.0 
                 24.8 
                 31.0 
                 17.0 
               
               
                 n (Samp) 
                 528 
                 287 
                 528 
                 152 
                 528 
                 67 
               
               
                 n (Patient) 
                 137 
                 287 
                 137 
                 152 
                 137 
                 67 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 5.51 
                 2.52 
                 5.51 
                 3.54 
                 5.51 
                 4.09 
               
               
                 Average 
                 6.27 
                 3.44 
                 6.27 
                 5.29 
                 6.27 
                 5.23 
               
               
                 Stdev 
                 4.55 
                 3.26 
                 4.55 
                 5.23 
                 4.55 
                 4.50 
               
               
                 p(t-test) 
                   
                 3.1E−10 
                   
                 0.077 
                   
                 0.13 
               
               
                 Min 
                 0.00291 
                 0.00597 
                 0.00291 
                 0.00439 
                 0.00291 
                 0.133 
               
               
                 Max 
                 31.0 
                 16.8 
                 31.0 
                 28.6 
                 31.0 
                 17.8 
               
               
                 n (Samp) 
                 1187 
                 109 
                 1187 
                 74 
                 1187 
                 45 
               
               
                 n (Patient) 
                 315 
                 109 
                 315 
                 74 
                 315 
                 45 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 4.14 
                 5.16 
                 4.14 
                 4.36 
                 4.14 
                 4.01 
               
               
                 Average 
                 5.01 
                 5.93 
                 5.01 
                 5.28 
                 5.01 
                 4.89 
               
               
                 Stdev 
                 4.12 
                 4.64 
                 4.12 
                 4.10 
                 4.12 
                 4.23 
               
               
                 p(t-test) 
                   
                 0.0031 
                   
                 0.48 
                   
                 0.82 
               
               
                 Min 
                 0.00439 
                 0.00291 
                 0.00439 
                 0.111 
                 0.00439 
                 0.0794 
               
               
                 Max 
                 31.0 
                 28.6 
                 31.0 
                 24.8 
                 31.0 
                 17.0 
               
               
                 n (Samp) 
                 685 
                 261 
                 685 
                 147 
                 685 
                 69 
               
               
                 n (Patient) 
                 172 
                 261 
                 172 
                 147 
                 172 
                 69 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.48 
                 0.29 
                 0.56 
                 0.45 
                 0.40 
                 0.52 
                 0.43 
                 0.42 
                 0.48 
               
               
                 SE 
                 0.021 
                 0.029 
                 0.021 
                 0.027 
                 0.036 
                 0.026 
                 0.038 
                 0.045 
                 0.037 
               
               
                 P 
                 0.43 
                 2.7E−13 
                 0.0055 
                 0.042 
                 0.0043 
                 0.36 
                 0.077 
                 0.072 
                 0.58 
               
               
                 nCohort 1 
                 528 
                 1187 
                 685 
                 528 
                 1187 
                 685 
                 528 
                 1187 
                 685 
               
               
                 nCohort 2 
                 287 
                 109 
                 261 
                 152 
                 74 
                 147 
                 67 
                 45 
                 69 
               
               
                 Cutoff 1 
                 2.65 
                 1.32 
                 2.82 
                 2.54 
                 2.57 
                 2.83 
                 2.44 
                 1.83 
                 2.21 
               
               
                 Sens 1 
                 70% 
                 71% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 71% 
                 71% 
               
               
                 Spec 1 
                 24% 
                 10% 
                 36% 
                 23% 
                 21% 
                 36% 
                 22% 
                 15% 
                 27% 
               
               
                 Cutoff 2 
                 1.71 
                 0.689 
                 1.96 
                 1.85 
                 2.08 
                 1.81 
                 1.71 
                 1.53 
                 1.40 
               
               
                 Sens 2 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
                 80% 
                 81% 
                 80% 
                 81% 
               
               
                 Spec 2 
                 16% 
                  5% 
                 25% 
                 17% 
                 17% 
                 23% 
                 16% 
                 12% 
                 18% 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 Cutoff 3 
                 0.673 
                 0.418 
                 1.14 
                 0.955 
                 0.905 
                 1.18 
                 0.706 
                 0.374 
                 0.396 
               
               
                 Sens 3 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 91% 
                 91% 
                 91% 
               
               
                 Spec 3 
                  6% 
                  4% 
                 15% 
                  9% 
                  7% 
                 16% 
                  7% 
                  3% 
                  7% 
               
               
                 Cutoff 4 
                 6.86 
                 7.65 
                 6.28 
                 6.86 
                 7.65 
                 6.28 
                 6.86 
                 7.65 
                 6.28 
               
               
                 Sens 4 
                 30% 
                 12% 
                 37% 
                 23% 
                 19% 
                 33% 
                 22% 
                 24% 
                 25% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 8.46 
                 9.56 
                 7.65 
                 8.46 
                 9.56 
                 7.65 
                 8.46 
                 9.56 
                 7.65 
               
               
                 Sens 5 
                 21% 
                  6% 
                 28% 
                 15% 
                 16% 
                 19% 
                 12% 
                 16% 
                 17% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 10.7 
                 12.3 
                 10.1 
                 10.7 
                 12.3 
                 10.1 
                 10.7 
                 12.3 
                 10.1 
               
               
                 Sens 6 
                 15% 
                  2% 
                 17% 
                 10% 
                 12% 
                 12% 
                  9% 
                 13% 
                 12% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.84 
                 2.5 
                 0.93 
                 1.0 
                 0.63 
                 1.2 
                 1.4 
                 1.0 
                 1.3 
               
               
                 p Value 
                 0.40 
                 0.044 
                 0.73 
                 0.89 
                 0.30 
                 0.60 
                 0.43 
                 1.0 
                 0.46 
               
               
                 95% CI of 
                 0.56 
                 1.0 
                 0.61 
                 0.60 
                 0.27 
                 0.68 
                 0.63 
                 0.39 
                 0.64 
               
               
                 OR Quart2 
                 1.3 
                 6.1 
                 1.4 
                 1.8 
                 1.5 
                 1.9 
                 3.0 
                 2.6 
                 2.7 
               
               
                 OR Quart 3 
                 0.82 
                 4.0 
                 1.2 
                 1.5 
                 1.6 
                 1.3 
                 1.5 
                 1.1 
                 1.1 
               
               
                 p Value 
                 0.35 
                 0.0015 
                 0.47 
                 0.15 
                 0.17 
                 0.30 
                 0.33 
                 0.82 
                 0.71 
               
               
                 95% CI of 
                 0.55 
                 1.7 
                 0.77 
                 0.87 
                 0.81 
                 0.79 
                 0.68 
                 0.45 
                 0.55 
               
               
                 OR Quart3 
                 1.2 
                 9.2 
                 1.8 
                 2.5 
                 3.2 
                 2.2 
                 3.2 
                 2.8 
                 2.4 
               
               
                 OR Quart 4 
                 1.2 
                 10 
                 1.5 
                 1.7 
                 2.2 
                 1.3 
                 2.0 
                 1.9 
                 1.2 
               
               
                 p Value 
                 0.39 
                 1.5E−8 
                 0.037 
                 0.040 
                 0.020 
                 0.36 
                 0.069 
                 0.11 
                 0.57 
               
               
                 95% CI of 
                 0.80 
                 4.5 
                 1.0 
                 1.0 
                 1.1 
                 0.76 
                 0.95 
                 0.85 
                 0.60 
               
               
                 OR Quart4 
                 1.8 
                 22 
                 2.3 
                 2.9 
                 4.2 
                 2.1 
                 4.2 
                 4.4 
                 2.5 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.10 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0 or R) and in urine samples collected from subjects at  
               
               
                 0, 24 hours, and 48 hours prior to reaching stage I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 Tyrosine-protein kinase receptor UFO 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 4.56 
                 4.92 
                 4.56 
                 4.61 
                 4.56 
                 4.72 
               
               
                 Average 
                 5.46 
                 5.96 
                 5.46 
                 5.44 
                 5.46 
                 5.81 
               
               
                 Stdev 
                 4.29 
                 5.18 
                 4.29 
                 4.04 
                 4.29 
                 4.51 
               
               
                 p(t-test) 
                   
                 0.16 
                   
                 0.97 
                   
                 0.50 
               
               
                 Min 
                 0.00439 
                 0.00597 
                 0.00439 
                 0.00291 
                 0.00439 
                 0.0794 
               
               
                 Max 
                 31.0 
                 28.6 
                 31.0 
                 24.1 
                 31.0 
                 20.8 
               
               
                 n (Samp) 
                 971 
                 183 
                 971 
                 133 
                 971 
                 76 
               
               
                 n (Patient) 
                 249 
                 183 
                 249 
                 133 
                 249 
                 76 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 5.16 
                 1.80 
                 5.16 
                 2.64 
                 5.16 
                 3.62 
               
               
                 Average 
                 5.98 
                 2.79 
                 5.98 
                 4.17 
                 5.98 
                 4.45 
               
               
                 Stdev 
                 4.54 
                 3.12 
                 4.54 
                 4.09 
                 4.54 
                 3.90 
               
               
                 p(t-test) 
                   
                 1.0E−7 
                   
                 0.0058 
                   
                 0.052 
               
               
                 Min 
                 0.00291 
                 4.21E−6 
                 0.00291 
                 0.00597 
                 0.00291 
                 0.0794 
               
               
                 Max 
                 31.0 
                 16.8 
                 31.0 
                 17.2 
                 31.0 
                 19.1 
               
               
                 n (Samp) 
                 1465 
                 59 
                 1465 
                 49 
                 1465 
                 34 
               
               
                 n (Patient) 
                 380 
                 59 
                 380 
                 49 
                 380 
                 34 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 4.12 
                 5.64 
                 4.12 
                 5.06 
                 4.12 
                 4.95 
               
               
                 Average 
                 5.14 
                 6.50 
                 5.14 
                 5.82 
                 5.14 
                 5.80 
               
               
                 Stdev 
                 4.28 
                 5.32 
                 4.28 
                 4.15 
                 4.28 
                 4.36 
               
               
                 p(t-test) 
                   
                 3.4E−4 
                   
                 0.10 
                   
                 0.22 
               
               
                 Min 
                 0.00439 
                 0.00597 
                 0.00439 
                 0.00291 
                 0.00439 
                 0.133 
               
               
                 Max 
                 31.0 
                 28.6 
                 31.0 
                 24.1 
                 31.0 
                 20.8 
               
               
                 n (Samp) 
                 1113 
                 156 
                 1113 
                 118 
                 1113 
                 67 
               
               
                 n (Patient) 
                 274 
                 156 
                 274 
                 118 
                 274 
                 67 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.51 
                 0.25 
                 0.57 
                 0.51 
                 0.36 
                 0.56 
                 0.52 
                 0.39 
                 0.55 
               
               
                 SE 
                 0.023 
                 0.037 
                 0.025 
                 0.027 
                 0.043 
                 0.029 
                 0.035 
                 0.052 
                 0.037 
               
               
                 P 
                 0.78 
                 3.0E−11 
                 0.0082 
                 0.82 
                 8.1E−4 
                 0.028 
                 0.61 
                 0.034 
                 0.18 
               
               
                 nCohort 1 
                 971 
                 1465 
                 1113 
                 971 
                 1465 
                 1113 
                 971 
                 1465 
                 1113 
               
               
                 nCohort 2 
                 183 
                 59 
                 156 
                 133 
                 49 
                 118 
                 76 
                 34 
                 67 
               
               
                 Cutoff 1 
                 2.08 
                 0.889 
                 2.72 
                 2.84 
                 1.47 
                 3.25 
                 2.71 
                 2.02 
                 2.71 
               
               
                 Sens 1 
                 70% 
                 71% 
                 71% 
                 71% 
                 71% 
                 70% 
                 71% 
                 71% 
                 70% 
               
               
                 Spec 1 
                 22% 
                  8% 
                 34% 
                 31% 
                 14% 
                 40% 
                 29% 
                 19% 
                 34% 
               
               
                 Cutoff 2 
                 1.46 
                 0.464 
                 1.74 
                 2.38 
                 0.745 
                 2.53 
                 2.18 
                 1.53 
                 1.90 
               
               
                 Sens 2 
                 80% 
                 81% 
                 80% 
                 80% 
                 82% 
                 81% 
                 80% 
                 82% 
                 81% 
               
               
                 Spec 2 
                 16% 
                  5% 
                 22% 
                 25% 
                  7% 
                 31% 
                 23% 
                 14% 
                 24% 
               
               
                 Cutoff 3 
                 0.773 
                 0.258 
                 0.800 
                 1.19 
                 0.374 
                 1.37 
                 1.40 
                 0.776 
                 1.34 
               
               
                 Sens 3 
                 90% 
                 92% 
                 90% 
                 90% 
                 92% 
                 91% 
                 91% 
                 91% 
                 91% 
               
               
                 Spec 3 
                  8% 
                  3% 
                 11% 
                 13% 
                  4% 
                 18% 
                 15% 
                  7% 
                 17% 
               
               
                 Cutoff 4 
                 6.78 
                 7.40 
                 6.47 
                 6.78 
                 7.40 
                 6.47 
                 6.78 
                 7.40 
                 6.47 
               
               
                 Sens 4 
                 33% 
                  8% 
                 39% 
                 30% 
                 24% 
                 33% 
                 29% 
                 15% 
                 31% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 8.40 
                 9.18 
                 7.95 
                 8.40 
                 9.18 
                 7.95 
                 8.40 
                 9.18 
                 7.95 
               
               
                 Sens 5 
                 27% 
                  3% 
                 33% 
                 20% 
                 14% 
                 25% 
                 21% 
                  6% 
                 22% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 10.7 
                 12.1 
                 10.5 
                 10.7 
                 12.1 
                 10.5 
                 10.7 
                 12.1 
                 10.5 
               
               
                 Sens 6 
                 19% 
                  2% 
                 22% 
                 10% 
                  8% 
                 13% 
                 14% 
                  6% 
                 16% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.49 
                 2.7 
                 0.78 
                 1.5 
                 0.30 
                 1.3 
                 0.94 
                 2.4 
                 1.0 
               
               
                 p Value 
                 0.0028 
                 0.14 
                 0.35 
                 0.15 
                 0.065 
                 0.36 
                 0.86 
                 0.22 
                 1.0 
               
               
                 95% CI of 
                 0.30 
                 0.71 
                 0.46 
                 0.87 
                 0.081 
                 0.72 
                 0.48 
                 0.61 
                 0.47 
               
               
                 OR Quart2 
                 0.78 
                 10 
                 1.3 
                 2.5 
                 1.1 
                 2.4 
                 1.8 
                 9.2 
                 2.1 
               
               
                 OR Quart 3 
                 0.65 
                 3.0 
                 1.1 
                 1.3 
                 1.3 
                 1.9 
                 1.00 
                 3.7 
                 1.5 
               
               
                 p Value 
                 0.059 
                 0.097 
                 0.80 
                 0.34 
                 0.53 
                 0.028 
                 0.99 
                 0.044 
                 0.23 
               
               
                 95% CI of 
                 0.42 
                 0.82 
                 0.65 
                 0.76 
                 0.57 
                 1.1 
                 0.51 
                 1.0 
                 0.77 
               
               
                 OR Quart3 
                 1.0 
                 11 
                 1.7 
                 2.2 
                 3.0 
                 3.4 
                 1.9 
                 14 
                 3.1 
               
               
                 OR Quart 4 
                 0.95 
                 14 
                 1.7 
                 1.3 
                 2.4 
                 1.9 
                 1.1 
                 4.5 
                 1.3 
               
               
                 p Value 
                 0.82 
                 1.0E−5 
                 0.019 
                 0.34 
                 0.024 
                 0.028 
                 0.88 
                 0.020 
                 0.47 
               
               
                 95% CI of 
                 0.63 
                 4.4 
                 1.1 
                 0.76 
                 1.1 
                 1.1 
                 0.55 
                 1.3 
                 0.64 
               
               
                 OR Quart4 
                 1.4 
                 47 
                 2.7 
                 2.2 
                 5.1 
                 3.4 
                 2.0 
                 16 
                 2.7 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.11 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected within 12 hours of 
               
               
                 reaching stage R from Cohort 1 (patients that reached, but did not progress beyond, 
               
               
                 RIFLE stage R) and from Cohort 2 (patients that reached RIFLE stage I or F). 
               
               
                   
               
             
            
               
                 Tyrosine-protein kinase receptor UFO 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 4.17 
                 5.43 
                 3.72 
                 2.10 
                 3.89 
                 5.61 
               
               
                 Average 
                 5.53 
                 6.10 
                 3.89 
                 3.74 
                 5.94 
                 6.18 
               
               
                 Stdev 
                 5.31 
                 4.95 
                 2.93 
                 3.82 
                 5.68 
                 4.75 
               
               
                 p(t-test) 
                   
                 0.52 
                   
                 0.88 
                   
                 0.78 
               
               
                 Min 
                 0.296 
                 0.00597 
                 0.296 
                 0.00597 
                 0.476 
                 0.00597 
               
               
                 Max 
                 28.2 
                 28.6 
                 10.4 
                 16.8 
                 28.2 
                 28.6 
               
               
                 n (Samp) 
                 46 
                 126 
                 22 
                 38 
                 49 
                 115 
               
               
                 n (Patient) 
                 46 
                 126 
                 22 
                 38 
                 49 
                 115 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.55 
                 0.45 
                 0.54 
               
               
                 SE 
                 0.049 
                 0.077 
                 0.049 
               
               
                 P 
                 0.34 
                 0.53 
                 0.40 
               
               
                 nCohort 1 
                 46 
                 22 
                 49 
               
               
                 nCohort 2 
                 126 
                 38 
                 115 
               
               
                 Cutoff 1 
                 2.74 
                 1.22 
                 2.78 
               
               
                 Sens 1 
                 71% 
                 71% 
                 70% 
               
               
                 Spec 1 
                 41% 
                 32% 
                 39% 
               
               
                 Cutoff 2 
                 1.90 
                 0.679 
                 2.13 
               
               
                 Sens 2 
                 80% 
                 82% 
                 80% 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 Spec 2 
                 35% 
                 23% 
                 33% 
               
               
                 Cutoff 3 
                 0.762 
                 0.367 
                 0.925 
               
               
                 Sens 3 
                 90% 
                 92% 
                 90% 
               
               
                 Spec 3 
                 17% 
                  5% 
                 12% 
               
               
                 Cutoff 4 
                 7.39 
                 5.55 
                 7.88 
               
               
                 Sens 4 
                 31% 
                 29% 
                 31% 
               
               
                 Spec 4 
                 72% 
                 73% 
                 71% 
               
               
                 Cutoff 5 
                 8.90 
                 7.20 
                 9.59 
               
               
                 Sens 5 
                 25% 
                 21% 
                 23% 
               
               
                 Spec 5 
                 80% 
                 82% 
                 82% 
               
               
                 Cutoff 6 
                 12.3 
                 7.39 
                 12.3 
               
               
                 Sens 6 
                 11% 
                 18% 
                 10% 
               
               
                 Spec 6 
                 91% 
                 91% 
                 92% 
               
               
                 OR Quart 2 
                 2.2 
                 0.44 
                 1.5 
               
               
                 p Value 
                 0.10 
                 0.28 
                 0.35 
               
               
                 95% CI of 
                 0.86 
                 0.10 
                 0.62 
               
               
                 OR Quart2 
                 5.8 
                 1.9 
                 3.9 
               
               
                 OR Quart 3 
                 1.7 
                 9.3 
                 2.0 
               
               
                 p Value 
                 0.25 
                 0.054 
                 0.16 
               
               
                 95% CI of 
                 0.69 
                 0.96 
                 0.77 
               
               
                 OR Quart3 
                 4.3 
                 91 
                 5.1 
               
               
                 OR Quart 4 
                 2.0 
                 1.0 
                 1.7 
               
               
                 p Value 
                 0.16 
                 1.0 
                 0.24 
               
               
                 95% CI of 
                 0.76 
                 0.23 
                 0.69 
               
               
                 OR Quart4 
                 5.0 
                 4.3 
                 4.4 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18.12 
               
               
                   
               
               
                 Comparison of the maximum marker levels in urine samples collected from 
               
               
                 Cohort 1 (patients that did not progress beyond RIFLE stage 0) and the maximum values 
               
               
                 in urine samples collected from subjects between enrollment and 0, 24 hours, and 48 
               
               
                 hours prior to reaching stage F in Cohort 2. 
               
               
                   
               
             
            
               
                 Tyrosine-protein kinase receptor UFO 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr or UO 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 7.82 
                 4.27 
                 7.82 
                 3.85 
                 7.82 
                 4.27 
               
               
                 Average 
                 8.83 
                 6.59 
                 8.83 
                 5.68 
                 8.83 
                 6.05 
               
               
                 Stdev 
                 4.43 
                 6.52 
                 4.43 
                 6.12 
                 4.43 
                 5.32 
               
               
                 p(t-test) 
                   
                 0.0093 
                   
                 4.5E−4 
                   
                 0.0077 
               
               
                 Min 
                 2.71 
                 0.341 
                 2.71 
                 0.142 
                 2.71 
                 0.157 
               
               
                 Max 
                 31.0 
                 28.6 
                 31.0 
                 28.6 
                 31.0 
                 22.1 
               
               
                 n (Samp) 
                 137 
                 47 
                 137 
                 39 
                 137 
                 23 
               
               
                 n (Patient) 
                 137 
                 47 
                 137 
                 39 
                 137 
                 23 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 sCr only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 7.87 
                 4.98 
                 7.87 
                 4.27 
                 7.87 
                 4.98 
               
               
                 Average 
                 9.08 
                 5.84 
                 9.08 
                 5.51 
                 9.08 
                 5.95 
               
               
                 Stdev 
                 4.98 
                 5.09 
                 4.98 
                 4.85 
                 4.98 
                 4.98 
               
               
                 p(t-test) 
                   
                 0.0011 
                   
                 6.1E−4 
                   
                 0.0099 
               
               
                 Min 
                 0.794 
                 0.367 
                 0.794 
                 0.367 
                 0.794 
                 0.367 
               
               
                 Max 
                 31.0 
                 22.1 
                 31.0 
                 22.1 
                 31.0 
                 22.1 
               
               
                 n (Samp) 
                 315 
                 28 
                 315 
                 25 
                 315 
                 18 
               
               
                 n (Patient) 
                 315 
                 28 
                 315 
                 25 
                 315 
                 18 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 7.10 
                 3.79 
                 7.10 
                 3.50 
                 7.10 
                 4.84 
               
               
                 Average 
                 8.03 
                 7.10 
                 8.03 
                 6.11 
                 8.03 
                 7.25 
               
               
                 Stdev 
                 4.59 
                 7.62 
                 4.59 
                 7.40 
                 4.59 
                 7.14 
               
               
                 p(t-test) 
                   
                 0.35 
                   
                 0.067 
                   
                 0.56 
               
               
                 Min 
                 0.611 
                 0.341 
                 0.611 
                 0.142 
                 0.611 
                 0.157 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 UO only 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Max 
                 31.0 
                 28.6 
                 31.0 
                 28.6 
                 31.0 
                 25.5 
               
               
                 n (Samp) 
                 172 
                 32 
                 172 
                 27 
                 172 
                 14 
               
               
                 n (Patient) 
                 172 
                 32 
                 172 
                 27 
                 172 
                 14 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                 AUC 
                 0.31 
                 0.28 
                 0.36 
                 0.25 
                 0.27 
                 0.30 
                 0.27 
                 0.28 
                 0.37 
               
               
                 SE 
                 0.047 
                 0.056 
                 0.056 
                 0.049 
                 0.059 
                 0.059 
                 0.063 
                 0.070 
                 0.083 
               
               
                 P 
                 4.3E−5 
                 1.3E−4 
                 0.016 
                 3.0E−7 
                 6.2E−5 
                 1.0E−3 
                 1.9E−4 
                 0.0016 
                 0.13 
               
               
                 nCohort 1 
                 137 
                 315 
                 172 
                 137 
                 315 
                 172 
                 137 
                 315 
                 172 
               
               
                 nCohort 2 
                 47 
                 28 
                 32 
                 39 
                 25 
                 27 
                 23 
                 18 
                 14 
               
               
                 Cutoff 1 
                 2.03 
                 2.99 
                 1.90 
                 1.96 
                 2.27 
                 1.63 
                 3.13 
                 3.62 
                 3.18 
               
               
                 Sens 1 
                 70% 
                 71% 
                 72% 
                 72% 
                 72% 
                 70% 
                 74% 
                 72% 
                 71% 
               
               
                 Spec 1 
                  0% 
                  7% 
                  5% 
                  0% 
                  3% 
                  3% 
                  3% 
                 11% 
                 12% 
               
               
                 Cutoff 2 
                 1.22 
                 1.03 
                 1.19 
                 1.13 
                 1.96 
                 1.02 
                 1.96 
                 3.10 
                 1.90 
               
               
                 Sens 2 
                 81% 
                 82% 
                 81% 
                 82% 
                 80% 
                 81% 
                 83% 
                 83% 
                 86% 
               
               
                 Spec 2 
                  0% 
                  0% 
                  2% 
                  0% 
                  3% 
                  1% 
                  0% 
                  7% 
                  5% 
               
               
                 Cutoff 3 
                 0.585 
                 0.794 
                 0.370 
                 0.367 
                 0.401 
                 0.341 
                 0.472 
                 0.367 
                 1.63 
               
               
                 Sens 3 
                 91% 
                 93% 
                 91% 
                 92% 
                 92% 
                 93% 
                 91% 
                 94% 
                 93% 
               
               
                 Spec 3 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  3% 
               
               
                 Cutoff 4 
                 10.4 
                 11.1 
                 9.35 
                 10.4 
                 11.1 
                 9.35 
                 10.4 
                 11.1 
                 9.35 
               
               
                 Sens 4 
                 21% 
                 14% 
                 25% 
                 13% 
                 12% 
                 15% 
                 13% 
                 11% 
                 21% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 11.8 
                 12.9 
                 11.4 
                 11.8 
                 12.9 
                 11.4 
                 11.8 
                 12.9 
                 11.4 
               
               
                 Sens 5 
                 19% 
                  7% 
                 25% 
                 13% 
                  4% 
                 15% 
                 13% 
                  6% 
                 21% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 14.4 
                 15.8 
                 14.0 
                 14.4 
                 15.8 
                 14.0 
                 14.4 
                 15.8 
                 14.0 
               
               
                 Sens 6 
                 15% 
                  7% 
                 19% 
                  8% 
                  4% 
                 11% 
                  9% 
                  6% 
                 14% 
               
               
                 Spec 6 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.44 
                 0.49 
                 0.34 
                 1.2 
                 0.66 
                 1.0 
                 0.65 
                 0.50 
                 0.33 
               
               
                 p Value 
                 0.17 
                 0.41 
                 0.12 
                 0.75 
                 0.65 
                 1.0 
                 0.65 
                 0.57 
                 0.34 
               
               
                 95% CI of 
                 0.14 
                 0.087 
                 0.084 
                 0.35 
                 0.11 
                 0.24 
                 0.10 
                 0.044 
                 0.033 
               
               
                 OR Quart2 
                 1.4 
                 2.7 
                 1.3 
                 4.4 
                 4.0 
                 4.2 
                 4.1 
                 5.6 
                 3.3 
               
               
                 OR Quart 3 
                 0.76 
                 2.1 
                 0.46 
                 1.2 
                 2.5 
                 0.73 
                 2.2 
                 3.2 
                 1.0 
               
               
                 p Value 
                 0.60 
                 0.24 
                 0.23 
                 0.75 
                 0.20 
                 0.70 
                 0.30 
                 0.16 
                 1.0 
               
               
                 95% CI of 
                 0.27 
                 0.61 
                 0.13 
                 0.35 
                 0.61 
                 0.16 
                 0.50 
                 0.63 
                 0.19 
               
               
                 OR Quart3 
                 2.1 
                 7.3 
                 1.6 
                 4.4 
                 9.8 
                 3.5 
                 9.4 
                 16 
                 5.2 
               
               
                 OR Quart 4 
                 3.9 
                 4.0 
                 2.7 
                 7.8 
                 4.9 
                 5.6 
                 5.3 
                 5.0 
                 2.6 
               
               
                 p Value 
                 0.0032 
                 0.018 
                 0.042 
                 2.6E−4 
                 0.016 
                 0.0044 
                 0.016 
                 0.044 
                 0.18 
               
               
                 95% CI of 
                 1.6 
                 1.3 
                 1.0 
                 2.6 
                 1.4 
                 1.7 
                 1.4 
                 1.0 
                 0.64 
               
               
                 OR Quart4 
                 9.7 
                 13 
                 7.0 
                 23 
                 18 
                 18 
                 21 
                 24 
                 11 
               
               
                   
               
            
           
         
       
     
     While the invention has been described and exemplified in sufficient detail for those skilled in this art to make and use it, various alternatives, modifications, and improvements should be apparent without departing from the spirit and scope of the invention. The examples provided herein are representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention. Modifications therein and other uses will occur to those skilled in the art. These modifications are encompassed within the spirit of the invention and are defined by the scope of the claims. 
     It will be readily apparent to a person skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. 
     All patents and publications mentioned in the specification are indicative of the levels of those of ordinary skill in the art to which the invention pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. 
     The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims. 
     Other embodiments are set forth within the following claims.