Patent Publication Number: US-10324093-B2

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

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present invention is filed under 35 U.S.C. § 371 as the U.S. national phase of International Application No. PCT/US2010/055730, filed Nov. 5, 2010, which designated the U.S. and claims the benefit of priority to U.S. Provisional Patent Application No. 61/259,163 filed Nov. 7, 2009; U.S. Provisional Patent Application No. 61/259,540filed Nov. 9, 2009; U.S. Provisional Patent Application No. 61/259,140 filed Nov. 7, 2009; U.S. Provisional Patent Application No. 61/259,142 filed Nov. 7, 2009; U.S. Provisional Patent Application No. 61/259,143 filed Nov. 7, 2009; U.S. Provisional Patent Application No. 61/259,141 filed Nov. 7, 2009; and U.S. Provisional Patent Application No. 61/259,511 filed Nov. 9, 2009, each of which is hereby incorporated in its entirety including all tables, figures, and claims. 
    
    
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 5, 2012, is named AST1250US_SequenceListing_txt and is 26,063 bytes in size. 
     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 biomarkers selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 (each referred to herein 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). 
     The kidney injury markers of the present invention 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 biomarkers selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 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) 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) 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) 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) 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) 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), for example measured concentration(s) of one or more biomarkers selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 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) 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) 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) 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) 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(s0 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 measured concentration(s) of one or more biomarkers selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 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) 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) 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) 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) 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 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 measured concentration(s) of one or more biomarkers selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 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) 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 creatnine 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 biomarkers selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 or one or more markers related thereto, 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.” 
     As used herein, the term “Cathepsin B” refers to one or more polypeptides present in a biological sample that are derived from the Cathepsin B precursor (Swiss-Prot P07858 (SEQ ID NO: 1)) 
     
       
         
           
               
               
            
               
                         10         20         30         40         50         60 
                   
               
               
                 MWQLWASLCC LLVLANARSR PSFHPLSDEL VNYVNKRNTT WQAGHNFYNV DMSYLKRLCG 
               
               
                   
               
               
                         70         80         90        100        110        120 
               
               
                 TFLGGPKPPQ RVMFTEDLKL PASFDAREQW PQCPTIKEIR DQGSCGSCWA FGAVEAISDR 
               
               
                   
               
               
                        130        140        150        160        170        180 
               
               
                 ICIHTNAHVS VEVSAEDLLT CCGSMCGDGC NGGYPAEAWN FWTRKGLVSG GLYESHVGCR 
               
               
                   
               
               
                        190        200        210        220        230        240 
               
               
                 PYSIPPCEHH VNGSRPPCTG EGDTPKCSKI CEPGYSPTYK QDKHYGYNSY SVSNSEKDIM 
               
               
                   
               
               
                        250        260        270        280        290        300 
               
               
                 AEIYKNGPVE GAFSVYSDFL LYKSGVYQHV TGEMMGGHAI RILGWGVENG TPYWLVANSW 
               
               
                   
               
               
                        310        320        330 
               
               
                 NTDWGDNGFF KILRGQDHCG IESEVVAGIP RTDQYWEKI 
               
            
           
         
       
     
     The following domains have been identified in Cathepsin B: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  1-17 
                 17 
                 signal peptide 
               
               
                   
                 18-79 
                 62 
                 activation peptide 
               
               
                   
                 334-339 
                 6 
                 propeptide 
               
               
                   
                  80-333 
                 254 
                 Cathepsin B 
               
               
                   
                  80-126 
                 47 
                 Cathepsin B light chain 
               
               
                   
                 129-333 
                 205 
                 Cathepsin B heavy chain 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “Renin” refers to one or more polypeptides present in a biological sample that are derived from the Renin precursor (Swiss-Prot P00797 (SEQ ID NO: 2)). 
     
       
         
           
               
               
            
               
                         10         20         30         40         50         60 
                   
               
               
                 MDGWRRMPRW GLLLLLWGSC TFGLPTDTTT FKRIFLKRMP SIRESLKERG VDMARLGPEW 
               
               
                   
               
               
                         70         80         90        100        110        120 
               
               
                 SQPMKRLTLG NTTSSVILTN YMDTQYYGEI GIGTPPQTFK VVFDTGSSNV WVPSSKCSRL 
               
               
                   
               
               
                        130        140        150        160        170        180 
               
               
                 YTACVYHKLF DASDSSSYKH NGTELTLRYS TGTVSGFLSQ DIITVGGITV TQMFGEVTEM 
               
               
                   
               
               
                        190        200        210        220        230        240 
               
               
                 PALPFMLAEF DGVVGMGFIE QAIGRVTPIF DNIISQGVLK EDVFSFYYNR DSENSQSLGG 
               
               
                   
               
               
                        250        260        270        280        290        300 
               
               
                 QIVLGGSDPQ HYEGNFHYIN LIKTGVWQIQ MKGVSVGSST LLCEDGCLAL VDTGASYISG 
               
               
                   
               
               
                        310        320        330        340        350        360 
               
               
                 STSSIEKLME ALGAKKRLFD YVVKCNEGPT LPDISFHLGG KEYTLTSADY VFQESYSSKK 
               
               
                   
               
               
                        370        380        390        400 
               
               
                 LCTLAIHAMD IPPPTGPTWA LGATFIRKFY TEFDRRNNRI GFALAR 
               
            
           
         
       
     
     The following domains have been identified in Renin: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  1-23 
                 23 
                 Propeptide 
               
               
                   
                 24-66 
                 43 
                 Activation peptide 
               
               
                   
                  67-406 
                 340 
                 Renin 
               
               
                   
                 231-233 
                 3 
                 Missing in isoform 2 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “Dipeptidyl peptidase 4” refers to one or more polypeptides present in a biological sample that are derived from the Dipeptidyl peptidase 4 precursor (Swiss-Prot P27487 (SEQ ID NO: 3)) 
     
       
         
           
               
               
            
               
                         10         20         30         40         50         60 
                   
               
               
                 MKTPWKVLLG LLGAAALVTI ITVPVVLLNK GTDDATADSR KTYTLTDYLK NTYRLKLYSL 
               
               
                   
               
               
                         70         80         90        100        110        120 
               
               
                 RWISDHEYLY KQENNILVFN AEYGNSSVFL ENSTFDEFGH SINDYSISPD GQFILLEYNY 
               
               
                   
               
               
                        130        140        150        160        170        180 
               
               
                 VKQWRHSYTA SYDIYDLNKR QLITEERIPN NTQWVTWSPV GHKLAYVWNN DIYVKIEPNL 
               
               
                   
               
               
                        190        200        210        220        230        240 
               
               
                 PSYRITWTGK EDIIYNGITD WVYEEEVFSA YSALWWSPNG TFLAYAQFND TEVPLIEYSF 
               
               
                   
               
               
                        250        260        270        280        290        300 
               
               
                 YSDESLQYPK TVRVPYPKAG AVNPTVKFFV VNTDSLSSVT NATSIQITAP ASMLIGDHYL 
               
               
                   
               
               
                        310        320        330        340        350        360 
               
               
                 CDVTWATQER ISLQWLRRIQ NYSVMDICDY DESSGRWNCL VARQHIEMST TGWVGRFRPS 
               
               
                   
               
               
                        370        380        390        400        410        420 
               
               
                 EPHFTLDGNS FYKIISNEEG YRHICYFQID KKDCTFITKG TWEVIGIEAL TSDYLYYISN 
               
               
                   
               
               
                        430        440        450        460        470        480 
               
               
                 EYKGMPGGRN LYKIQLSDYT KVTCLSCELN PERCQYYSVS FSKEAKYYQL RCSGPGLPLY 
               
               
                   
               
               
                        490        500        510        520        530        540 
               
               
                 TLHSSVNDKG LRVLEDNSAL DKMLQNVQMP SKKLDFIILN ETKFWYQMIL PPHFDKSKKY 
               
               
                   
               
               
                        550        560        570        580        590        600 
               
               
                 PLLLDVYAGP CSQKADTVFR LNWATYLAST ENIIVASFDG RGSGYQGDKI MHAINRRLGT 
               
               
                   
               
               
                        610        620        630        640        650        660 
               
               
                 FEVEDQIEAA RQFSKMGFVD NKRIAIWGWS YGGYVTSMVL GSGSGVFKCG IAVAPVSRWE 
               
               
                   
               
               
                        670        680        690        700        710        720 
               
               
                 YYDSVYTERY MGLPTPEDNL DHYRNSTVMS RAENFKQVEY LLIHGTADDN VHFQQSAQIS 
               
               
                   
               
               
                        730        740        750        760 
               
               
                 KALVDVGVDF QAMWYTDEDH GIASSTAHQH IYTHMSHFIK QCFSLP 
               
            
           
         
       
     
     Most preferably, the Dipeptidyl peptidase 4 assay detects one or more soluble forms of Dipeptidyl peptidase 4. Dipeptidyl peptidase 4 is a type II membrane protein having a large extracellular domain, most or all of which is present in soluble forms of Dipeptidyl peptidase 4 generated either through alternative splicing event which deletes all or a portion of the transmembrane domain, or by proteolysis of the membrane-bound form. In the case of an immunoassay, one or more antibodies that bind to epitopes within this extracellular domain may be used to detect these soluble form(s). The following domains have been identified in Dipeptidyl peptidase 4: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  1-766 
                 766 
                 Dipeptidyl peptidase 4 
               
               
                   
                 39-766 
                 728 
                 Dipeptidyl peptidase 4, soluble form 
               
               
                   
                 1-6  
                 6 
                 Cytoplasmic 
               
               
                   
                 7-28 
                 22 
                 Anchor signal 
               
               
                   
                 29-766 
                 738 
                 Extracellular 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “Neprilysin” refers to one or more polypeptides present in a biological sample that are derived from the Neprilysin precursor (Swiss-Prot P08473 (SEQ ID NO: 4)) 
     
       
         
           
               
               
            
               
                        10          20         30         40         50         60 
                   
               
               
                 MGKSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 
               
               
                   
               
               
                         70         80         90        100        110        120 
               
               
                 DCIKSAARLI QNMDATTEPC TDFFKYACGG WLKRNVIPET SSRYGNFDIL RDELEVVLKD 
               
               
                   
               
               
                        130        140        150        160        170        180 
               
               
                 VLQEPKTEDI VAVQKAKALY RSCINESAID SRGGEPLLKL LPDIYGWPVA TENWEQKYGA 
               
               
                   
               
               
                        190        200        210        220        230        240 
               
               
                 SWTAEKAIAQ LNSKYGKKVL INLFVGTDDK NSVNHVIHID QPRLGLPSRD YYECTGIYKE 
               
               
                   
               
               
                        250        260        270        280        290        300 
               
               
                 ACTAYVDFMI SVARLIRQEE RLPIDENQLA LEMNKVMELE KEIANATAKP EDRNDPMLLY 
               
               
                   
               
               
                        310        320        330        340        350        360 
               
               
                 NKMTLAQIQN NFSLEINGKP FSWLNFTNEI MSTVNISITN EEDVVVYAPE YLTKLKPILT 
               
               
                   
               
               
                        370        380        390        400        410        420 
               
               
                 KYSARDLQNL MSWRFIMDLV SSLSRTYKES RNAFRKALYG TTSETATWRR CANYVNGNME 
               
               
                   
               
               
                        430        440        450        460        470        480 
               
               
                 NAVGRLYVEA AFAGESKHVV EDLIAQIREV FIQTLDDLTW MDAETKKRAE EKALAIKERI 
               
               
                   
               
               
                        490        500        510        520        530        540 
               
               
                 GYPDDIVSND NKLNNEYLEL NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 
               
               
                   
               
               
                        550        560        570        580        590        600 
               
               
                 VVNAFYSSGR NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 
               
               
                   
               
               
                        610        620        630        640        650        660 
               
               
                 GDLVDWWTQQ SASNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA DNGGLGQAYR 
               
               
                   
               
               
                        670        680        690        700        710        720 
               
               
                 AYQNYIKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP EYAVNSIKTD VHSPGNFRII 
               
               
                   
               
               
                        730        740        750 
               
               
                 GTLQNSAEFS EAFHCRKNSY MNPEKKCRVW 
               
            
           
         
       
     
     Most preferably, the Neprilysin assay detects one or more soluble forms of Neprilysin. Neprilysin is a type II membrane protein having a large extracellular domain, most or all of which is present in soluble forms of Neprilysin generated either through alternative splicing event which deletes all or a portion of the transmembrane domain, or by proteolysis of the membrane-bound form. In the case of an immunoassay, one or more antibodies that bind to epitopes within this extracellular domain may be used to detect these soluble form(s). The following domains have been identified in Neprilysin: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 1 
                 1 
                 initiator methionine 
               
               
                   
                  2-750 
                 749 
                 Neprilysin 
               
               
                   
                 2-28 
                 27 
                 Cytoplasmic 
               
               
                   
                 29-51  
                 23 
                 Anchor signal 
               
               
                   
                 52-750 
                 699 
                 Extracellular 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “Beta-2-microglobulin” refers to one or more polypeptides present in a biological sample that are derived from the Beta-2-microglobulin precursor (Swiss-Prot P61769 (SEQ ID NO: 5)) 
     
       
         
           
               
               
            
               
                         10         20         30         40         50         60 
                   
               
               
                 MSRSVALAVL ALLSLSGLEA IQRTPKIQVY SRHPAENGKS NFLNCYVSGF HPSDIEVDLL 
               
               
                   
               
               
                         70         80         90        100        110 
               
               
                 KNGERIEKVE HSDLSFSKDW SFYLLYYTEF TPTEKDEYAC RVNHVTLSQP KIVKWDRDM 
               
            
           
         
       
     
     The following domains have been identified in Beta-2-microglobulin: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 1-20 
                 20 
                 signal peptide 
               
               
                   
                 21-119 
                 99 
                 Beta-2-microglobulin 
               
               
                   
                 22-119 
                 21 
                 Beta-2-microglobulin form pI 5.3 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “Carbonic anhydrase IX” refers to one or more polypeptides present in a biological sample that are derived from the Carbonic anhydrase IX precursor (Swiss-Prot Q16790 (SEQ ID NO: 6)) 
     
       
         
           
               
               
            
               
                         10         20         30         40         50         60 
                   
               
               
                 MAPLCPSPWL PLLIPAPAPG LTVQLLLSLL LLVPVHPQRL PRMQEDSPLG GGSSGEDDPL 
               
               
                   
               
               
                         70         80         90        100        110        120 
               
               
                 GEEDLPSEED SPREEDPPGE EDLPGEEDLP GEEDLPEVKP KSEEEGSLKL EDLPTVEAPG 
               
               
                   
               
               
                        130        140        150        160        170        180 
               
               
                 DPQEPQNNAH RDKEGDDQSH WRYGGDPPWP RVSPACAGRF QSPVDIRPQL AAFCPALRPL 
               
               
                   
               
               
                        190        200        210        220        230        240 
               
               
                 ELLGFQLPPL PELRLRNNGH SVQLTLPPGL EMALGPGREY RALQLHLHWG AAGRPGSEHT 
               
               
                   
               
               
                        250        260        270        280        290        300 
               
               
                 VEGHRFPAEI HVVHLSTAFA RVDEALGRPG GLAVLAAFLE EGPEENSAYE QLLSRLEEIA 
               
               
                   
               
               
                        310        320        330        340        350        360 
               
               
                 EEGSETQVPG LDISALLPSD FSRYFQYEGS LTTPPCAQGV IWTVFNQTVM LSAKQLHTLS 
               
               
                   
               
               
                        370        380        390        400        410        420 
               
               
                 DTLWGPGDSR LQLNFRATQP LNGRVIEASF PAGVDSSPRA AEPVQLNSCL AAGDILALVF 
               
               
                   
               
               
                        430        440        450 
               
               
                 GLLFAVTSVA FLVQMRRQHR RGTKGGVSYR PAEVAETGA 
               
            
           
         
       
     
     Most preferably, the Carbonic anhydrase IX assay detects one or more soluble forms of Carbonic anhydrase IX. Carbonic anhydrase IX is a type I membrane protein having a large extracellular domain, most or all of which is present in soluble forms of Carbonic anhydrase IX generated either through alternative splicing event which deletes all or a portion of the transmembrane domain, or by proteolysis of the membrane-bound form. In the case of an immunoassay, one or more antibodies that bind to epitopes within this extracellular domain may be used to detect these soluble form(s). The following domains have been identified in Carbonic anhydrase IX: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 1-37 
                 37 
                 Signal peptide 
               
               
                   
                 38-459 
                 422 
                 Carbonic anhydrase IX 
               
               
                   
                 38-414 
                 377 
                 Extracellular 
               
               
                   
                 415-435  
                 21 
                 Transmembrane domain 
               
               
                   
                 436-459  
                 699 
                 Cytoplasmic 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “C-X-C motif chemokine 2” refers to one or more polypeptides present in a biological sample that are derived from the C-X-C motif chemokine 2 precursor (Swiss-Prot P19875 (SEQ ID NO: 7)). 
     
       
         
           
               
               
            
               
                         10         20         30         40         50         60 
                   
               
               
                 MARATLSAAP SNPRLLRVAL LLLLLVAASR RAAGAPLATE LRCQCLQTLQ GIHLKNIQSV 
               
               
                   
               
               
                         70         80         90        100 
               
               
                 KVKSPGPHCA QTEVIATLKN GQKACLNPAS PMVKKIIEKM LKNGKSN 
               
            
           
         
       
     
     The following domains have been identified in C-X-C motif chemokine 2: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Residues 
                 Length 
                 Domain ID 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 1-34 
                 34 
                 Signal peptide 
               
               
                   
                 35-107 
                 73 
                 C-X-C motif chemokine 2 
               
               
                   
                 39-107 
                 69 
                 GRO-beta 
               
               
                   
                   
               
            
           
         
       
     
     As used herein, the term “relating a signal to the presence or amount” of an analyte reflects the following 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. 
     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. 
     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 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, TentaGel™ resins (Rapp Polymere GmbH), AgroGel™ resins (I.L.S.A. Industria Lavorazione Sottoprodotti Animali S.P.A.), polyethylene glycol and acrylamide (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 CHl 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 CHl 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. 
     While the present application describes antibody-based binding assays in detail, alternatives to antibodies as binding species in assays are well known in the art. These include receptors for a particular target, aptamers, etc. Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist. High-affinity aptamers containing modified nucleotides conferring improved characteristics on the ligand, such as improved in vivo stability or improved delivery characteristics. Examples of such modifications include chemical substitutions at the ribose and/or phosphate and/or base positions, and may include amino acid side chain functionalities. 
     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 97.5th 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 detection 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 (P61679); Beta-galactosidase (P16278); BMP-7 (P18075); Brain natriuretic peptide (proBNP, BNP-32, NTproBNP; P16860); Calcium-binding protein Beta (S100-beta, P04271); Carbonic anhydrase (Q16790); Casein Kinase 2 (P68400); Ceruloplasmin (P00450); 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, P02793; heavy chain P02794); Fructose-1,6-biphosphatase (P09467); GRO-alpha (CXCL1, (P09341); Growth Hormone (P01241); Hepatocyte growth factor (P14210); Insulin-like growth factor I (P01343); Immunoglobulin G; Immunoglobulin Light Chains (Kappa and Lambda); Interferon gamma (P01308); Lysozyme (P61626); Interleukin-1alpha (P01583); Interleukin-2 (P60568); Interleukin-4 (P60568); 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 (P10451); 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-Beta1 (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 (Itm 1, 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, O43656); L-arginine:glycine amidinotransferase (P50440); Leptin (P41159); Lipocalin2 (NGAL, P80188); MCP-1 (P13500); MIG (Gamma-interferon-induced monokine Q07325); MIP-1a (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 (Q86U61); 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: 
     
       
         
           
             
               G 
               ⁢ 
               
                   
               
               ⁢ 
               F 
               ⁢ 
               
                   
               
               ⁢ 
               R 
             
             = 
             
               
                 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 
               
               
                 B 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 S 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 A 
               
             
           
         
       
     
     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. Concentrations reported below are as follows: Cathepsin B ng/mL; Renin pg/mL; Dipeptidyl Peptidase IV (soluble form) ng/mL; Neprilysin (soluble form) ng/mL; Beta-2-microglobulin μg/mL; Carbonic anhydrase IX (soluble form) ng/mL; and C-X-C motif chemokine 2 pg/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 Kidney Injury Markers for Evaluating Renal Status in Patients 
     Patients from the intensive care unit (ICU) were enrolled in the following study. Each patient was 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 a urine samples (25-30 mL) were 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. Markers were each 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 were 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 was generated for each biomarker measured and the area under each ROC curve (AUC) is determined. Patients in Cohort 2 were 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 was 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 threshold (or “cutoff”) concentrations were 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 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. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.44 
                 4.76 
                 1.44 
                 2.61 
                 1.44 
                 4.70 
               
               
                 Average 
                 2.57 
                 3.52 
                 2.57 
                 2.83 
                 2.57 
                 3.36 
               
               
                 Stdev 
                 2.43 
                 2.58 
                 2.43 
                 2.53 
                 2.43 
                 2.39 
               
               
                 p(t-test) 
                   
                 0.014 
                   
                 0.48 
                   
                 0.11 
               
               
                 Min 
                 0.00152 
                 0.00403 
                 0.00152 
                 0.00212 
                 0.00152 
                 0.0378 
               
               
                 Max 
                 6.10 
                 6.10 
                 6.10 
                 6.07 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 255 
                 48 
                 255 
                 57 
                 255 
                 27 
               
               
                 n (Patient) 
                 103 
                 48 
                 103 
                 57 
                 103 
                 27 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.43 
                 0.462 
                 1.43 
                 0.763 
                 1.43 
                 1.24 
               
               
                 Average 
                 2.59 
                 2.48 
                 2.59 
                 2.51 
                 2.59 
                 2.07 
               
               
                 Stdev 
                 2.45 
                 2.78 
                 2.45 
                 2.68 
                 2.45 
                 2.33 
               
               
                 p(t-test) 
                   
                 0.86 
                   
                 0.89 
                   
                 0.45 
               
               
                 Min 
                 0.00152 
                 0.00925 
                 0.00152 
                 0.0114 
                 0.00152 
                 0.0324 
               
               
                 Max 
                 6.10 
                 6.10 
                 6.10 
                 5.80 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 447 
                 16 
                 447 
                 21 
                 447 
                 13 
               
               
                 n (Patient) 
                 170 
                 16 
                 170 
                 21 
                 170 
                 13 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.39 
                 4.57 
                 1.39 
                 2.61 
                 1.39 
                 4.82 
               
               
                 Average 
                 2.56 
                 3.58 
                 2.56 
                 2.90 
                 2.56 
                 3.51 
               
               
                 Stdev 
                 2.44 
                 2.45 
                 2.44 
                 2.50 
                 2.44 
                 2.41 
               
               
                 p(t-test) 
                   
                 0.010 
                   
                 0.37 
                   
                 0.064 
               
               
                 Min 
                 0.00152 
                 0.00403 
                 0.00152 
                 0.00212 
                 0.00152 
                 0.0378 
               
               
                 Max 
                 6.10 
                 6.10 
                 6.10 
                 6.07 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 218 
                 46 
                 218 
                 51 
                 218 
                 25 
               
               
                 n (Patient) 
                 87 
                 46 
                 87 
                 51 
                 87 
                 25 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.45 
                 0.60 
                 0.51 
                 0.46 
                 0.51 
                 0.57 
                 0.45 
                 0.58 
               
               
                 SE 
                 0.046 
                 0.075 
                 0.048 
                 0.043 
                 0.066 
                 0.045 
                 0.060 
                 0.083 
                 0.063 
               
               
                 p 
                 0.044 
                 0.53 
                 0.031 
                 0.83 
                 0.59 
                 0.79 
                 0.25 
                 0.55 
                 0.19 
               
               
                 nCohort 1 
                 255 
                 447 
                 218 
                 255 
                 447 
                 218 
                 255 
                 447 
                 218 
               
               
                 nCohort 2 
                 48 
                 16 
                 46 
                 57 
                 21 
                 51 
                 27 
                 13 
                 25 
               
               
                 Cutoff 1 
                 0.734 
                 0.0999 
                 1.48 
                 0.278 
                 0.153 
                 0.278 
                 1.22 
                 0.171 
                 1.02 
               
               
                 Sens 1 
                 71% 
                 75% 
                 72% 
                 70% 
                 71% 
                 71% 
                 70% 
                 77% 
                 72% 
               
               
                 Spec 1 
                 40% 
                 17% 
                 51% 
                 27% 
                 21% 
                 27% 
                 48% 
                 23% 
                 46% 
               
               
                 Cutoff 2 
                 0.0999 
                 0.0513 
                 0.278 
                 0.0999 
                 0.0851 
                 0.152 
                 0.213 
                 0.0743 
                 0.354 
               
               
                 Sens 2 
                 81% 
                 81% 
                 80% 
                 81% 
                 81% 
                 80% 
                 81% 
                 85% 
                 80% 
               
               
                 Spec 2 
                 14% 
                 11% 
                 27% 
                 14% 
                 15% 
                 19% 
                 24% 
                 14% 
                 31% 
               
               
                 Cutoff 3 
                 0.0273 
                 0.0197 
                 0.0298 
                 0.0246 
                 0.0372 
                 0.0168 
                 0.0683 
                 0.0683 
                 0.141 
               
               
                 Sens 3 
                 92% 
                 94% 
                 91% 
                 91% 
                 90% 
                 90% 
                 93% 
                 92% 
                 92% 
               
               
                 Spec 3 
                  4% 
                  4% 
                  5% 
                  3% 
                  8% 
                  2% 
                 10% 
                 13% 
                 18% 
               
               
                 Cutoff 4 
                 5.08 
                 5.13 
                 5.16 
                 5.08 
                 5.13 
                 5.16 
                 5.08 
                 5.13 
                 5.16 
               
               
                 Sens 4 
                 48% 
                 38% 
                 43% 
                 37% 
                 38% 
                 37% 
                 41% 
                 23% 
                 36% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
               
               
                 Sens 5 
                 17% 
                  6% 
                 17% 
                  2% 
                  0% 
                  2% 
                  0% 
                  0% 
                  0% 
               
               
                 Spec 5 
                 95% 
                 95% 
                 94% 
                 95% 
                 95% 
                 94% 
                 95% 
                 95% 
                 94% 
               
               
                 Cutoff 6 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
               
               
                 Sens 6 
                 17% 
                  6% 
                 17% 
                  2% 
                  0% 
                  2% 
                  0% 
                  0% 
                  0% 
               
               
                 Spec 6 
                 95% 
                 95% 
                 94% 
                 95% 
                 95% 
                 94% 
                 95% 
                 95% 
                 94% 
               
               
                 OR Quart 2 
                 0.41 
                 0.39 
                 0.52 
                 0.57 
                 0.49 
                 0.51 
                 0.47 
                 1.0 
                 0.57 
               
               
                 p Value 
                 0.12 
                 0.27 
                 0.26 
                 0.20 
                 0.32 
                 0.17 
                 0.30 
                 1.0 
                 0.45 
               
               
                 95% CI of 
                 0.14 
                 0.074 
                 0.16 
                 0.24 
                 0.12 
                 0.20 
                 0.11 
                 0.20 
                 0.13 
               
               
                 OR Quart2 
                 1.2 
                 2.0 
                 1.6 
                 1.3 
                 2.0 
                 1.3 
                 2.0 
                 5.1 
                 2.5 
               
               
                 OR Quart 3 
                 1.1 
                 0.59 
                 2.2 
                 0.85 
                 0.83 
                 1.4 
                 1.8 
                 1.0 
                 1.9 
               
               
                 p Value 
                 0.85 
                 0.48 
                 0.084 
                 0.68 
                 0.76 
                 0.42 
                 0.29 
                 1.0 
                 0.28 
               
               
                 95% CI of 
                 0.45 
                 0.14 
                 0.90 
                 0.38 
                 0.24 
                 0.63 
                 0.61 
                 0.20 
                 0.60 
               
               
                 OR Quart3 
                 2.7 
                 2.5 
                 5.4 
                 1.9 
                 2.8 
                 3.1 
                 5.2 
                 5.1 
                 6.1 
               
               
                 OR Quart 4 
                 2.1 
                 1.2 
                 1.9 
                 1.1 
                 1.2 
                 0.73 
                 1.4 
                 1.3 
                 1.7 
               
               
                 p Value 
                 0.080 
                 0.75 
                 0.18 
                 0.84 
                 0.78 
                 0.48 
                 0.59 
                 0.70 
                 0.40 
               
               
                 95% CI of 
                 0.92 
                 0.36 
                 0.75 
                 0.50 
                 0.38 
                 0.30 
                 0.44 
                 0.29 
                 0.51 
               
               
                 OR Quart4 
                 4.7 
                 4.1 
                 4.6 
                 2.3 
                 3.6 
                 1.8 
                 4.1 
                 6.2 
                 5.4 
               
               
                   
               
            
           
           
               
            
               
                 C-X-C motif chemokine 2 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.135 
                 2.51 
                 0.135 
                 4.01 
                 0.135 
                 0.0260 
               
               
                   
                 Average 
                 8.01 
                 11.4 
                 8.01 
                 12.4 
                 8.01 
                 7.85 
               
               
                   
                 Stdev 
                 26.5 
                 27.8 
                 26.5 
                 30.9 
                 26.5 
                 19.6 
               
               
                   
                 p(t-test) 
                   
                 0.32 
                   
                 0.17 
                   
                 0.97 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 111 
               
               
                   
                 n (Samp) 
                 360 
                 75 
                 360 
                 91 
                 360 
                 43 
               
               
                   
                 n (Patient) 
                 190 
                 75 
                 190 
                 91 
                 190 
                 43 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.536 
                 2.64 
                 0.536 
                 4.37 
                 0.536 
                 3.34 
               
               
                   
                 Average 
                 8.92 
                 17.6 
                 8.92 
                 17.4 
                 8.92 
                 6.53 
               
               
                   
                 Stdev 
                 25.5 
                 42.4 
                 25.5 
                 40.9 
                 25.5 
                 8.89 
               
               
                   
                 p(t-test) 
                   
                 0.083 
                   
                 0.058 
                   
                 0.65 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 36.2 
               
               
                   
                 n (Samp) 
                 755 
                 29 
                 755 
                 37 
                 755 
                 23 
               
               
                   
                 n (Patient) 
                 295 
                 29 
                 295 
                 37 
                 295 
                 23 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.262 
                 2.64 
                 0.262 
                 5.28 
                 0.262 
                 0.0260 
               
               
                   
                 Average 
                 7.67 
                 12.4 
                 7.67 
                 14.9 
                 7.67 
                 9.52 
               
               
                   
                 Stdev 
                 25.1 
                 29.6 
                 25.1 
                 33.2 
                 25.1 
                 21.4 
               
               
                   
                 p(t-test) 
                   
                 0.18 
                   
                 0.035 
                   
                 0.67 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 111 
               
               
                   
                 n (Samp) 
                 315 
                 65 
                 315 
                 78 
                 315 
                 36 
               
               
                   
                 n (Patient) 
                 134 
                 65 
                 134 
                 78 
                 134 
                 36 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.61 
                 0.61 
                 0.62 
                 0.62 
                 0.61 
                 0.64 
                 0.49 
                 0.57 
                 0.49 
               
               
                 SE 
                 0.037 
                 0.057 
                 0.040 
                 0.034 
                 0.050 
                 0.037 
                 0.047 
                 0.063 
                 0.051 
               
               
                 p 
                 0.0039 
                 0.049 
                 0.0025 
                   5.8E−4 
                 0.025 
                 9.7E−5 
                 0.82 
                 0.27 
                 0.83 
               
               
                 nCohort 1 
                 360 
                 755 
                 315 
                 360 
                 755 
                 315 
                 360 
                 755 
                 315 
               
               
                 nCohort 2 
                 75 
                 29 
                 65 
                 91 
                 37 
                 78 
                 43 
                 23 
                 36 
               
               
                 Cutoff 1 
                 0.00804 
                 0.244 
                 0.299 
                 0.00804 
                 0.00804 
                 0.299 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                 Sens 1 
                 100%  
                 72% 
                 71% 
                 100%  
                 100%  
                 71% 
                 100%  
                 100%  
                 100%  
               
               
                 Spec 1 
                  0% 
                 46% 
                 51% 
                  0% 
                  0% 
                 51% 
                  0% 
                  0% 
                  0% 
               
               
                 Cutoff 2 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                 Sens 2 
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
               
               
                 Spec 2 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
               
               
                 Cutoff 3 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                 Sens 3 
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
               
               
                 Spec 3 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
               
               
                 Cutoff 4 
                 3.08 
                 3.96 
                 3.82 
                 3.08 
                 3.96 
                 3.82 
                 3.08 
                 3.96 
                 3.82 
               
               
                 Sens 4 
                 45% 
                 38% 
                 45% 
                 52% 
                 54% 
                 55% 
                 37% 
                 43% 
                 28% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 6.49 
                 7.98 
                 7.00 
                 6.49 
                 7.98 
                 7.00 
                 6.49 
                 7.98 
                 7.00 
               
               
                 Sens 5 
                 36% 
                 31% 
                 38% 
                 37% 
                 35% 
                 40% 
                 23% 
                 30% 
                 25% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 15.4 
                 20.2 
                 14.9 
                 15.4 
                 20.2 
                 14.9 
                 15.4 
                 20.2 
                 14.9 
               
               
                 Sens 6 
                 23% 
                 21% 
                 25% 
                 19% 
                 22% 
                 24% 
                 19% 
                  4% 
                 25% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.14 
                 &gt;9.4 
                 0.25 
                 &gt;44 
                 &gt;13 
                 3.1 
                 0.89 
                 &gt;9.4 
                 0.76 
               
               
                 p Value 
                 4.8E−4 
                 &lt;0.034 
                 0.010 
                 &lt;2.2E−4 
                 &lt;0.015 
                 0.015 
                 0.81 
                 &lt;0.034 
                 0.60 
               
               
                 95% CI of 
                 0.047 
                 &gt;1.2 
                 0.090 
                 &gt;5.9 
                 &gt;1.6 
                 1.2 
                 0.35 
                 &gt;1.2 
                 0.27 
               
               
                 OR Quart2 
                 0.42 
                 na 
                 0.72 
                 na 
                 na 
                 7.8 
                 2.3 
                 na 
                 2.1 
               
               
                 OR Quart 3 
                 0.78 
                 &gt;12 
                 1.1 
                 &gt;30 
                 &gt;11 
                 3.3 
                 0.78 
                 &gt;5.1 
                 0.10 
               
               
                 p Value 
                 0.47 
                 &lt;0.019 
                 0.85 
                 &lt;9.4E−4 
                 &lt;0.025 
                 0.0097 
                 0.62 
                 &lt;0.14 
                 0.031 
               
               
                 95% CI of 
                 0.40 
                 &gt;1.5 
                 0.51 
                 &gt;4.0 
                 &gt;1.3 
                 1.3 
                 0.30 
                 &gt;0.59 
                 0.012 
               
               
                 OR Quart3 
                 1.5 
                 na 
                 2.2 
                 na 
                 na 
                 8.3 
                 2.1 
                 na 
                 0.81 
               
               
                 OR Quart 4 
                 1.3 
                 &gt;9.4 
                 1.6 
                 &gt;50 
                 &gt;16 
                 6.2 
                 1.7 
                 &gt;9.4 
                 2.5 
               
               
                 p Value 
                 0.36 
                 &lt;0.034 
                 0.16 
                 &lt;1.3E−4 
                 &lt;0.0073 
                 4.4E−5 
                 0.20 
                 &lt;0.034 
                 0.040 
               
               
                 95% CI of 
                 0.72 
                 &gt;1.2 
                 0.82 
                 &gt;6.7 
                 &gt;2.1 
                 2.6 
                 0.75 
                 &gt;1.2 
                 1.0 
               
               
                 OR Quart4 
                 2.5 
                 na 
                 3.3 
                 na 
                 na 
                 15 
                 4.0 
                 na 
                 5.8 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 319 
                 494 
                 319 
                 483 
                 319 
                 323 
               
               
                   
                 Average 
                 750 
                 886 
                 750 
                 1350 
                 750 
                 1120 
               
               
                   
                 Stdev 
                 1270 
                 1110 
                 1270 
                 3110 
                 1270 
                 1660 
               
               
                   
                 p(t-test) 
                   
                 0.53 
                   
                 0.073 
                   
                 0.20 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 9810 
                 5150 
                 9810 
                 21100 
                 9810 
                 5550 
               
               
                   
                 n (Samp) 
                 121 
                 45 
                 121 
                 50 
                 121 
                 26 
               
               
                   
                 n (Patient) 
                 98 
                 45 
                 98 
                 50 
                 98 
                 26 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 394 
                 254 
                 394 
                 565 
                 394 
                 304 
               
               
                   
                 Average 
                 978 
                 1150 
                 978 
                 1340 
                 978 
                 985 
               
               
                   
                 Stdev 
                 1840 
                 1760 
                 1840 
                 1670 
                 1840 
                 1460 
               
               
                   
                 p(t-test) 
                   
                 0.75 
                   
                 0.40 
                   
                 0.99 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 21100 
                 4570 
                 21100 
                 5380 
                 21100 
                 4250 
               
               
                   
                 n (Samp) 
                 259 
                 12 
                 259 
                 19 
                 259 
                 13 
               
               
                   
                 n (Patient) 
                 159 
                 12 
                 159 
                 19 
                 159 
                 13 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 297 
                 638 
                 297 
                 606 
                 297 
                 385 
               
               
                   
                 Average 
                 758 
                 996 
                 758 
                 1540 
                 758 
                 1290 
               
               
                   
                 Stdev 
                 1340 
                 1100 
                 1340 
                 3230 
                 1340 
                 1710 
               
               
                   
                 p(t-test) 
                   
                 0.31 
                   
                 0.035 
                   
                 0.10 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 9810 
                 5150 
                 9810 
                 21100 
                 9810 
                 5550 
               
               
                   
                 n (Samp) 
                 106 
                 42 
                 106 
                 46 
                 106 
                 23 
               
               
                   
                 n (Patient) 
                 82 
                 42 
                 82 
                 46 
                 82 
                 23 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.46 
                 0.64 
                 0.57 
                 0.56 
                 0.63 
                 0.53 
                 0.47 
                 0.59 
               
               
                 SE 
                 0.051 
                 0.087 
                 0.052 
                 0.049 
                 0.070 
                 0.051 
                 0.063 
                 0.083 
                 0.068 
               
               
                 p 
                 0.12 
                 0.65 
                 0.0072 
                 0.13 
                 0.42 
                 0.012 
                 0.59 
                 0.76 
                 0.21 
               
               
                 nCohort 1 
                 121 
                 259 
                 106 
                 121 
                 259 
                 106 
                 121 
                 259 
                 106 
               
               
                 nCohort 2 
                 45 
                 12 
                 42 
                 50 
                 19 
                 46 
                 26 
                 13 
                 23 
               
               
                 Cutoff 1 
                 234 
                 161 
                 279 
                 203 
                 84.2 
                 211 
                 123 
                 137 
                 123 
               
               
                 Sens 1 
                 71% 
                 75% 
                 71% 
                 70% 
                 74% 
                 72% 
                 73% 
                 77% 
                 74% 
               
               
                 Spec 1 
                 40% 
                 29% 
                 46% 
                 38% 
                 20% 
                 41% 
                 31% 
                 28% 
                 32% 
               
               
                 Cutoff 2 
                 177 
                 34.5 
                 224 
                 111 
                 34.5 
                 134 
                 10.6 
                 0 
                 10.6 
               
               
                 Sens 2 
                 80% 
                 83% 
                 81% 
                 80% 
                 84% 
                 80% 
                 81% 
                 100%  
                 83% 
               
               
                 Spec 2 
                 36% 
                 15% 
                 41% 
                 30% 
                 15% 
                 33% 
                 21% 
                  0% 
                 20% 
               
               
                 Cutoff 3 
                 10.1 
                 0 
                 131 
                 65.6 
                 0 
                 88.6 
                 0 
                 0 
                 7.32 
               
               
                 Sens 3 
                 91% 
                 100%  
                 90% 
                 90% 
                 100%  
                 91% 
                 100%  
                 100%  
                 91% 
               
               
                 Spec 3 
                 21% 
                  0% 
                 33% 
                 27% 
                  0% 
                 28% 
                  0% 
                  0% 
                 18% 
               
               
                 Cutoff 4 
                 606 
                 881 
                 600 
                 606 
                 881 
                 600 
                 606 
                 881 
                 600 
               
               
                 Sens 4 
                 44% 
                 25% 
                 52% 
                 42% 
                 42% 
                 50% 
                 31% 
                 31% 
                 39% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 71% 
                 70% 
                 70% 
                 71% 
                 70% 
                 70% 
                 71% 
               
               
                 Cutoff 5 
                 1130 
                 1590 
                 1130 
                 1130 
                 1590 
                 1130 
                 1130 
                 1590 
                 1130 
               
               
                 Sens 5 
                 22% 
                 25% 
                 29% 
                 30% 
                 37% 
                 35% 
                 31% 
                 23% 
                 39% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 1990 
                 2390 
                 2060 
                 1990 
                 2390 
                 2060 
                 1990 
                 2390 
                 2060 
               
               
                 Sens 6 
                 13% 
                 25% 
                 14% 
                 16% 
                 16% 
                 22% 
                 23% 
                 15% 
                 22% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
               
               
                 OR Quart 2 
                 2.9 
                 0.66 
                 6.1 
                 2.1 
                 0.15 
                 2.5 
                 0.97 
                 0.66 
                 0.56 
               
               
                 p Value 
                 0.052 
                 0.65 
                 0.0089 
                 0.16 
                 0.085 
                 0.11 
                 0.96 
                 0.65 
                 0.45 
               
               
                 95% CI of 
                 0.99 
                 0.11 
                 1.6 
                 0.75 
                 0.018 
                 0.81 
                 0.28 
                 0.11 
                 0.12 
               
               
                 OR Quart2 
                 8.6 
                 4.1 
                 24 
                 5.6 
                 1.3 
                 7.5 
                 3.3 
                 4.1 
                 2.6 
               
               
                 OR Quart 3 
                 2.1 
                 1.4 
                 5.4 
                 1.6 
                 0.65 
                 2.5 
                 0.97 
                 1.7 
                 1.2 
               
               
                 p Value 
                 0.18 
                 0.70 
                 0.015 
                 0.34 
                 0.51 
                 0.11 
                 0.96 
                 0.47 
                 0.74 
               
               
                 95% CI of 
                 0.71 
                 0.29 
                 1.4 
                 0.59 
                 0.17 
                 0.81 
                 0.28 
                 0.39 
                 0.34 
               
               
                 OR Quart3 
                 6.5 
                 6.3 
                 21 
                 4.6 
                 2.4 
                 7.5 
                 3.3 
                 7.5 
                 4.6 
               
               
                 OR Quart 4 
                 2.9 
                 1.0 
                 6.9 
                 2.5 
                 1.4 
                 3.9 
                 1.4 
                 1.0 
                 2.0 
               
               
                 p Value 
                 0.052 
                 0.99 
                 0.0052 
                 0.067 
                 0.59 
                 0.014 
                 0.59 
                 1.0 
                 0.26 
               
               
                 95% CI of 
                 0.99 
                 0.20 
                 1.8 
                 0.94 
                 0.44 
                 1.3 
                 0.43 
                 0.19 
                 0.60 
               
               
                 OR Quart4 
                 8.6 
                 5.2 
                 27 
                 6.8 
                 4.1 
                 11 
                 4.5 
                 5.1 
                 6.9 
               
               
                   
               
            
           
           
               
            
               
                 Cathepsin B 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.504 
                 0.628 
                 0.504 
                 1.15 
                 0.504 
                 0.649 
               
               
                   
                 Average 
                 2.26 
                 1.84 
                 2.26 
                 5.00 
                 2.26 
                 4.06 
               
               
                   
                 Stdev 
                 8.48 
                 2.68 
                 8.48 
                 11.8 
                 8.48 
                 15.2 
               
               
                   
                 p(t-test) 
                   
                 0.74 
                   
                 0.084 
                   
                 0.40 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 72.4 
                 11.0 
                 72.4 
                 64.9 
                 72.4 
                 78.1 
               
               
                   
                 n (Samp) 
                 131 
                 47 
                 131 
                 50 
                 131 
                 26 
               
               
                   
                 n (Patient) 
                 102 
                 47 
                 102 
                 50 
                 102 
                 26 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.657 
                 0.485 
                 0.657 
                 1.92 
                 0.657 
                 0.338 
               
               
                   
                 Average 
                 2.89 
                 1.92 
                 2.89 
                 4.95 
                 2.89 
                 1.27 
               
               
                   
                 Stdev 
                 9.57 
                 2.68 
                 9.57 
                 7.48 
                 9.57 
                 1.85 
               
               
                   
                 p(t-test) 
                   
                 0.71 
                   
                 0.36 
                   
                 0.55 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 0.0682 
               
               
                   
                 Max 
                 78.1 
                 7.84 
                 78.1 
                 29.7 
                 78.1 
                 6.19 
               
               
                   
                 n (Samp) 
                 269 
                 14 
                 269 
                 19 
                 269 
                 13 
               
               
                   
                 n (Patient) 
                 162 
                 14 
                 162 
                 19 
                 162 
                 13 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.539 
                 0.951 
                 0.539 
                 1.32 
                 0.539 
                 0.846 
               
               
                   
                 Average 
                 2.37 
                 2.21 
                 2.37 
                 5.79 
                 2.37 
                 5.24 
               
               
                   
                 Stdev 
                 8.90 
                 2.91 
                 8.90 
                 12.6 
                 8.90 
                 16.1 
               
               
                   
                 p(t-test) 
                   
                 0.91 
                   
                 0.052 
                   
                 0.23 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 72.4 
                 11.6 
                 72.4 
                 64.9 
                 72.4 
                 78.1 
               
               
                   
                 n (Samp) 
                 118 
                 44 
                 118 
                 46 
                 118 
                 23 
               
               
                   
                 n (Patient) 
                 87 
                 44 
                 87 
                 46 
                 87 
                 23 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.56 
                 0.48 
                 0.62 
                 0.63 
                 0.67 
                 0.65 
                 0.50 
                 0.46 
                 0.56 
               
               
                 SE 
                 0.050 
                 0.080 
                 0.051 
                 0.048 
                 0.070 
                 0.050 
                 0.062 
                 0.084 
                 0.067 
               
               
                 p 
                 0.25 
                 0.83 
                 0.021 
                 0.0072 
                 0.015 
                 0.0032 
                 0.98 
                 0.64 
                 0.41 
               
               
                 nCohort 1 
                 131 
                 269 
                 118 
                 131 
                 269 
                 118 
                 131 
                 269 
                 118 
               
               
                 nCohort 2 
                 47 
                 14 
                 44 
                 50 
                 19 
                 46 
                 26 
                 13 
                 23 
               
               
                 Cutoff 1 
                 0.339 
                 0.142 
                 0.546 
                 0.665 
                 0.797 
                 0.665 
                 0.185 
                 0.265 
                 0.185 
               
               
                 Sens 1 
                 70% 
                 71% 
                 70% 
                 70% 
                 74% 
                 72% 
                 73% 
                 77% 
                 74% 
               
               
                 Spec 1 
                 40% 
                 18% 
                 51% 
                 58% 
                 55% 
                 56% 
                 21% 
                 28% 
                 21% 
               
               
                 Cutoff 2 
                 0.140 
                 0.0513 
                 0.309 
                 0.245 
                 0.265 
                 0.268 
                 0.105 
                 0.128 
                 0.0764 
               
               
                 Sens 2 
                 81% 
                 86% 
                 82% 
                 80% 
                 84% 
                 80% 
                 81% 
                 85% 
                 83% 
               
               
                 Spec 2 
                 18% 
                 14% 
                 37% 
                 30% 
                 28% 
                 31% 
                 17% 
                 17% 
                 12% 
               
               
                 Cutoff 3 
                 0 
                 0 
                 0.0764 
                 0 
                 0 
                 0 
                 0 
                 0.0901 
                 0 
               
               
                 Sens 3 
                 100%  
                 100%  
                 91% 
                 100%  
                 100%  
                 100%  
                 100%  
                 92% 
                 100%  
               
               
                 Spec 3 
                  0% 
                  0% 
                 12% 
                  0% 
                  0% 
                  0% 
                  0% 
                 15% 
                  0% 
               
               
                 Cutoff 4 
                 1.16 
                 1.35 
                 1.17 
                 1.16 
                 1.35 
                 1.17 
                 1.16 
                 1.35 
                 1.17 
               
               
                 Sens 4 
                 36% 
                 36% 
                 45% 
                 50% 
                 63% 
                 54% 
                 27% 
                 23% 
                 39% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 1.81 
                 2.07 
                 2.02 
                 1.81 
                 2.07 
                 2.02 
                 1.81 
                 2.07 
                 2.02 
               
               
                 Sens 5 
                 28% 
                 36% 
                 30% 
                 38% 
                 42% 
                 41% 
                 19% 
                 23% 
                 30% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
               
               
                 Cutoff 6 
                 3.53 
                 4.65 
                 3.53 
                 3.53 
                 4.65 
                 3.53 
                 3.53 
                 4.65 
                 3.53 
               
               
                 Sens 6 
                 19% 
                 14% 
                 20% 
                 26% 
                 26% 
                 28% 
                 15% 
                  8% 
                 30% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
               
               
                 OR Quart 2 
                 0.85 
                 0.19 
                 2.9 
                 0.44 
                 1.5 
                 0.49 
                 1.7 
                 1.0 
                 0.24 
               
               
                 p Value 
                 0.75 
                 0.13 
                 0.071 
                 0.16 
                 0.65 
                 0.25 
                 0.36 
                 0.99 
                 0.092 
               
               
                 95% CI of 
                 0.31 
                 0.021 
                 0.91 
                 0.14 
                 0.25 
                 0.15 
                 0.54 
                 0.20 
                 0.047 
               
               
                 OR Quart2 
                 2.3 
                 1.7 
                 9.2 
                 1.4 
                 9.4 
                 1.6 
                 5.3 
                 5.2 
                 1.3 
               
               
                 OR Quart 3 
                 1.4 
                 0.38 
                 3.0 
                 1.9 
                 1.5 
                 1.8 
                 0.47 
                 1.4 
                 1.0 
               
               
                 p Value 
                 0.47 
                 0.26 
                 0.062 
                 0.17 
                 0.65 
                 0.22 
                 0.31 
                 0.70 
                 1.0 
               
               
                 95% CI of 
                 0.55 
                 0.072 
                 0.94 
                 0.76 
                 0.25 
                 0.69 
                 0.11 
                 0.29 
                 0.31 
               
               
                 OR Quart3 
                 3.7 
                 2.0 
                 9.5 
                 4.9 
                 9.4 
                 4.9 
                 2.0 
                 6.3 
                 3.2 
               
               
                 OR Quart 4 
                 1.7 
                 1.2 
                 4.0 
                 2.5 
                 6.3 
                 2.8 
                 1.5 
                 1.0 
                 0.97 
               
               
                 p Value 
                 0.27 
                 0.74 
                 0.016 
                 0.054 
                 0.019 
                 0.037 
                 0.52 
                 0.99 
                 0.95 
               
               
                 95% CI of 
                 0.66 
                 0.36 
                 1.3 
                 0.99 
                 1.3 
                 1.1 
                 0.46 
                 0.20 
                 0.30 
               
               
                 OR Quart4 
                 4.3 
                 4.3 
                 13 
                 6.2 
                 30 
                 7.3 
                 4.7 
                 5.2 
                 3.1 
               
               
                   
               
            
           
           
               
            
               
                 Neprilysin 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 1.26 
                 0.949 
                 1.26 
                 1.03 
                 nd 
                 nd 
               
               
                   
                 Average 
                 4.09 
                 2.29 
                 4.09 
                 5.48 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 8.95 
                 3.70 
                 8.95 
                 13.1 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.40 
                   
                 0.60 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.0532 
                 0.0313 
                 0.0532 
                 0.0902 
                 nd 
                 nd 
               
               
                   
                 Max 
                 51.0 
                 16.0 
                 51.0 
                 46.3 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 62 
                 19 
                 62 
                 19 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 50 
                 19 
                 50 
                 19 
                 nd 
                 nd 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.963 
                 0.949 
                 0.963 
                 0.896 
                 nd 
                 nd 
               
               
                   
                 Average 
                 2.98 
                 2.47 
                 2.98 
                 5.23 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 6.67 
                 4.11 
                 6.67 
                 12.8 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.78 
                   
                 0.33 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.0532 
                 0.0313 
                 0.0532 
                 0.0203 
                 nd 
                 nd 
               
               
                   
                 Max 
                 35.3 
                 16.0 
                 35.3 
                 46.3 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 52 
                 15 
                 52 
                 20 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 41 
                 15 
                 41 
                 20 
                 nd 
                 nd 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.43 
                 nd 
                 0.47 
                 0.47 
                 nd 
                 0.50 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.077 
                 nd 
                 0.086 
                 0.077 
                 nd 
                 0.077 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 0.38 
                 nd 
                 0.69 
                 0.74 
                 nd 
                 0.99 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 62 
                 nd 
                 52 
                 62 
                 nd 
                 52 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 19 
                 nd 
                 15 
                 19 
                 nd 
                 20 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 0.279 
                 nd 
                 0.376 
                 0.586 
                 nd 
                 0.690 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 74% 
                 nd 
                 73% 
                 74% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                  8% 
                 nd 
                 15% 
                 23% 
                 nd 
                 31% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 0.238 
                 nd 
                 0.251 
                 0.351 
                 nd 
                 0.461 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 84% 
                 nd 
                 80% 
                 84% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                  8% 
                 nd 
                  8% 
                 15% 
                 nd 
                 21% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 0.117 
                 nd 
                 0.0869 
                 0.178 
                 nd 
                 0.306 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 95% 
                 nd 
                 93% 
                 95% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                  5% 
                 nd 
                  4% 
                  6% 
                 nd 
                 10% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 1.99 
                 nd 
                 1.45 
                 1.99 
                 nd 
                 1.45 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 37% 
                 nd 
                 33% 
                 21% 
                 nd 
                 35% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 71% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 3.50 
                 nd 
                 2.26 
                 3.50 
                 nd 
                 2.26 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 21% 
                 nd 
                 33% 
                 16% 
                 nd 
                 15% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 81% 
                 nd 
                 81% 
                 81% 
                 nd 
                 81% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 10.1 
                 nd 
                 4.43 
                 10.1 
                 nd 
                 4.43 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                  5% 
                 nd 
                 13% 
                 11% 
                 nd 
                 10% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 0.44 
                 nd 
                 0.51 
                 1.4 
                 nd 
                 1.8 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.30 
                 nd 
                 0.42 
                 0.65 
                 nd 
                 0.46 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.094 
                 nd 
                 0.10 
                 0.32 
                 nd 
                 0.40 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 2.1 
                 nd 
                 2.6 
                 6.3 
                 nd 
                 7.7 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 0.44 
                 nd 
                 0.32 
                 1.1 
                 nd 
                 1.3 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.30 
                 nd 
                 0.22 
                 0.94 
                 nd 
                 0.70 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.094 
                 nd 
                 0.053 
                 0.23 
                 nd 
                 0.30 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 2.1 
                 nd 
                 1.9 
                 5.0 
                 nd 
                 6.1 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 1.3 
                 nd 
                 1.1 
                 1.8 
                 nd 
                 1.3 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.66 
                 nd 
                 0.91 
                 0.42 
                 nd 
                 0.70 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.36 
                 nd 
                 0.25 
                 0.43 
                 nd 
                 0.30 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 5.0 
                 nd 
                 4.8 
                 7.8 
                 nd 
                 6.1 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
            
               
                 Carbonic anhydrase IX 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.00525 
                 0.00780 
                 0.00525 
                 0.0170 
                 nd 
                 nd 
               
               
                   
                 Average 
                 0.0125 
                 0.0158 
                 0.0125 
                 0.0706 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 0.0182 
                 0.0196 
                 0.0182 
                 0.193 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.51 
                   
                 0.020 
                 nd 
                 nd 
               
               
                   
                 Min 
                 1.00E−9 
                 0.000522 
                 1.00E−9 
                 0.00216 
                 nd 
                 nd 
               
               
                   
                 Max 
                 0.119 
                 0.0760 
                 0.119 
                 0.859 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 62 
                 19 
                 62 
                 19 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 50 
                 19 
                 50 
                 19 
                 nd 
                 nd 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.00432 
                 0.0111 
                 0.00432 
                 0.0204 
                 nd 
                 nd 
               
               
                   
                 Average 
                 0.0112 
                 0.0178 
                 0.0112 
                 0.0693 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 0.0189 
                 0.0211 
                 0.0189 
                 0.188 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.25 
                   
                 0.029 
                 nd 
                 nd 
               
               
                   
                 Min 
                 1.00E−9 
                 0.000522 
                 1.00E−9 
                 0.00216 
                 nd 
                 nd 
               
               
                   
                 Max 
                 0.119 
                 0.0760 
                 0.119 
                 0.859 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 52 
                 15 
                 52 
                 20 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 41 
                 15 
                 41 
                 20 
                 nd 
                 nd 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.54 
                 nd 
                 0.63 
                 0.73 
                 nd 
                 0.81 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.077 
                 nd 
                 0.085 
                 0.072 
                 nd 
                 0.063 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 0.60 
                 nd 
                 0.12 
                 0.0017 
                 nd 
                 8.1E−7 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 62 
                 nd 
                 52 
                 62 
                 nd 
                 52 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 19 
                 nd 
                 15 
                 19 
                 nd 
                 20 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 0.00269 
                 nd 
                 0.00444 
                 0.0102 
                 nd 
                 0.0158 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 74% 
                 nd 
                 73% 
                 74% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 26% 
                 nd 
                 52% 
                 61% 
                 nd 
                 83% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 0.00187 
                 nd 
                 0.00269 
                 0.00548 
                 nd 
                 0.0114 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 84% 
                 nd 
                 80% 
                 84% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 15% 
                 nd 
                 35% 
                 52% 
                 nd 
                 71% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 0.000712 
                 nd 
                 0.00105 
                 0.00337 
                 nd 
                 0.00548 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 95% 
                 nd 
                 93% 
                 95% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                  6% 
                 nd 
                 13% 
                 32% 
                 nd 
                 56% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 0.0121 
                 nd 
                 0.0114 
                 0.0121 
                 nd 
                 0.0114 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 42% 
                 nd 
                 47% 
                 58% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 71% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 0.0183 
                 nd 
                 0.0143 
                 0.0183 
                 nd 
                 0.0143 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 32% 
                 nd 
                 47% 
                 42% 
                 nd 
                 75% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 81% 
                 nd 
                 81% 
                 81% 
                 nd 
                 81% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 0.0293 
                 nd 
                 0.0212 
                 0.0293 
                 nd 
                 0.0212 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                 16% 
                 nd 
                 20% 
                 26% 
                 nd 
                 50% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 1.0 
                 nd 
                 1.5 
                 3.4 
                 nd 
                 2.1 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 1.0 
                 nd 
                 0.68 
                 0.31 
                 nd 
                 0.55 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.21 
                 nd 
                 0.22 
                 0.32 
                 nd 
                 0.18 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 4.7 
                 nd 
                 10 
                 35 
                 nd 
                 26 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 1.3 
                 nd 
                 1.5 
                 10 
                 nd 
                 8.5 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.71 
                 nd 
                 0.68 
                 0.039 
                 nd 
                 0.061 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.30 
                 nd 
                 0.22 
                 1.1 
                 nd 
                 0.90 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 5.9 
                 nd 
                 10 
                 93 
                 nd 
                 80 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 1.6 
                 nd 
                 4.9 
                 12 
                 nd 
                 27 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.52 
                 nd 
                 0.078 
                 0.028 
                 nd 
                 0.0039 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.38 
                 nd 
                 0.84 
                 1.3 
                 nd 
                 2.9 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 6.8 
                 nd 
                 29 
                 110 
                 nd 
                 250 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
            
               
                 Dipeptidyl peptidase IV 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 147 
                 435 
                 147 
                 237 
                 147 
                 239 
               
               
                 Average 
                 7480 
                 1090 
                 7480 
                 423 
                 7480 
                 852 
               
               
                 Stdev 
                 67000 
                 2170 
                 67000 
                 468 
                 67000 
                 1110 
               
               
                 p(t-test) 
                   
                 0.60 
                   
                 0.53 
                   
                 0.64 
               
               
                 Min 
                 0.200 
                 0.899 
                 0.200 
                 3.65 
                 0.200 
                 2.62 
               
               
                 Max 
                 677000 
                 11000 
                 677000 
                 1480 
                 677000 
                 4320 
               
               
                 n (Samp) 
                 102 
                 31 
                 102 
                 36 
                 102 
                 22 
               
               
                 n (Patient) 
                 82 
                 31 
                 82 
                 36 
                 82 
                 22 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 266 
                 147 
                 266 
                 130 
                 266 
                 96.7 
               
               
                 Average 
                 4260 
                 927 
                 4260 
                 672 
                 4260 
                 1030 
               
               
                 Stdev 
                 47800 
                 2100 
                 47800 
                 1270 
                 47800 
                 1670 
               
               
                 p(t-test) 
                   
                 0.82 
                   
                 0.80 
                   
                 0.84 
               
               
                 Min 
                 0.200 
                 6.52 
                 0.200 
                 18.2 
                 0.200 
                 10.1 
               
               
                 Max 
                 677000 
                 7150 
                 677000 
                 4460 
                 677000 
                 4950 
               
               
                 n (Samp) 
                 201 
                 11 
                 201 
                 12 
                 201 
                 9 
               
               
                 n (Patient) 
                 131 
                 11 
                 131 
                 12 
                 131 
                 9 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 121 
                 577 
                 121 
                 312 
                 121 
                 328 
               
               
                 Average 
                 536 
                 1260 
                 536 
                 463 
                 536 
                 888 
               
               
                 Stdev 
                 1240 
                 2270 
                 1240 
                 451 
                 1240 
                 1120 
               
               
                 p(t-test) 
                   
                 0.030 
                   
                 0.74 
                   
                 0.24 
               
               
                 Min 
                 0.200 
                 0.899 
                 0.200 
                 3.65 
                 0.200 
                 2.62 
               
               
                 Max 
                 9980 
                 11000 
                 9980 
                 1410 
                 9980 
                 4320 
               
               
                 n (Samp) 
                 93 
                 28 
                 93 
                 35 
                 93 
                 20 
               
               
                 n (Patient) 
                 71 
                 28 
                 71 
                 35 
                 71 
                 20 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.57 
                 0.48 
                 0.63 
                 0.53 
                 0.49 
                 0.60 
                 0.61 
                 0.53 
                 0.65 
               
               
                 SE 
                 0.060 
                 0.091 
                 0.063 
                 0.057 
                 0.086 
                 0.058 
                 0.069 
                 0.100 
                 0.072 
               
               
                 p 
                 0.23 
                 0.79 
                 0.038 
                 0.60 
                 0.91 
                 0.086 
                 0.12 
                 0.79 
                 0.038 
               
               
                 nCohort 1 
                 102 
                 201 
                 93 
                 102 
                 201 
                 93 
                 102 
                 201 
                 93 
               
               
                 nCohort 2 
                 31 
                 11 
                 28 
                 36 
                 12 
                 35 
                 22 
                 9 
                 20 
               
               
                 Cutoff 1 
                 58.9 
                 58.9 
                 62.9 
                 58.9 
                 52.2 
                 104 
                 93.8 
                 78.9 
                 95.2 
               
               
                 Sens 1 
                 71% 
                 73% 
                 71% 
                 72% 
                 75% 
                 71% 
                 73% 
                 78% 
                 70% 
               
               
                 Spec 1 
                 37% 
                 32% 
                 39% 
                 37% 
                 31% 
                 49% 
                 44% 
                 35% 
                 47% 
               
               
                 Cutoff 2 
                 20.7 
                 52.2 
                 19.1 
                 36.5 
                 42.6 
                 52.2 
                 83.4 
                 52.2 
                 83.4 
               
               
                 Sens 2 
                 81% 
                 82% 
                 82% 
                 81% 
                 83% 
                 80% 
                 82% 
                 89% 
                 80% 
               
               
                 Spec 2 
                 24% 
                 31% 
                 23% 
                 29% 
                 29% 
                 35% 
                 41% 
                 31% 
                 44% 
               
               
                 Cutoff 3 
                 6.52 
                 12.4 
                 6.36 
                 9.55 
                 36.5 
                 9.55 
                 42.6 
                 9.55 
                 42.6 
               
               
                 Sens 3 
                 90% 
                 91% 
                 93% 
                 92% 
                 92% 
                 91% 
                 91% 
                 100%  
                 90% 
               
               
                 Spec 3 
                 12% 
                 15% 
                 12% 
                 15% 
                 26% 
                 15% 
                 34% 
                 13% 
                 33% 
               
               
                 Cutoff 4 
                 538 
                 677 
                 407 
                 538 
                 677 
                 407 
                 538 
                 677 
                 407 
               
               
                 Sens 4 
                 48% 
                 27% 
                 61% 
                 33% 
                 25% 
                 40% 
                 36% 
                 33% 
                 45% 
               
               
                 Spec 4 
                 71% 
                 70% 
                 71% 
                 71% 
                 70% 
                 71% 
                 71% 
                 70% 
                 71% 
               
               
                 Cutoff 5 
                 1110 
                 1110 
                 698 
                 1110 
                 1110 
                 698 
                 1110 
                 1110 
                 698 
               
               
                 Sens 5 
                 23% 
                 18% 
                 43% 
                 11% 
                 17% 
                 26% 
                 32% 
                 33% 
                 40% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
               
               
                 Cutoff 6 
                 1960 
                 1990 
                 1560 
                 1960 
                 1990 
                 1560 
                 1960 
                 1990 
                 1560 
               
               
                 Sens 6 
                 13% 
                  9% 
                 18% 
                  0% 
                  8% 
                  0% 
                 14% 
                 11% 
                 25% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.83 
                 1.0 
                 0.23 
                 1.9 
                 1.0 
                 0.66 
                 4.2 
                 5.3 
                 2.8 
               
               
                 p Value 
                 0.76 
                 1.0 
                 0.088 
                 0.29 
                 0.98 
                 0.52 
                 0.089 
                 0.13 
                 0.24 
               
               
                 95% CI of 
                 0.24 
                 0.14 
                 0.044 
                 0.59 
                 0.14 
                 0.19 
                 0.80 
                 0.60 
                 0.50 
               
               
                 OR Quart2 
                 2.8 
                 7.4 
                 1.2 
                 5.9 
                 7.5 
                 2.4 
                 22 
                 47 
                 16 
               
               
                 OR Quart 3 
                 1.2 
                 2.7 
                 1.0 
                 1.9 
                 4.0 
                 2.1 
                 2.8 
                 0 
                 2.8 
               
               
                 p Value 
                 0.77 
                 0.26 
                 1.0 
                 0.26 
                 0.096 
                 0.18 
                 0.24 
                 na 
                 0.24 
               
               
                 95% CI of 
                 0.38 
                 0.49 
                 0.30 
                 0.62 
                 0.78 
                 0.71 
                 0.50 
                 na 
                 0.50 
               
               
                 OR Quart3 
                 3.8 
                 14 
                 3.3 
                 6.1 
                 20 
                 6.5 
                 16 
                 na 
                 16 
               
               
                 OR Quart 4 
                 1.5 
                 1.0 
                 2.1 
                 1.9 
                 0.50 
                 1.9 
                 5.0 
                 3.1 
                 5.0 
               
               
                 p Value 
                 0.44 
                 1.0 
                 0.20 
                 0.29 
                 0.58 
                 0.27 
                 0.054 
                 0.34 
                 0.058 
               
               
                 95% CI of 
                 0.51 
                 0.14 
                 0.68 
                 0.59 
                 0.044 
                 0.62 
                 0.98 
                 0.31 
                 0.95 
               
               
                 OR Quart4 
                 4.7 
                 7.4 
                 6.3 
                 5.9 
                 5.7 
                 5.7 
                 26 
                 30 
                 26 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 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. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.75 
                 3.29 
                 1.75 
                 0.538 
                 1.75 
                 0.362 
               
               
                 Average 
                 2.67 
                 2.85 
                 2.67 
                 2.11 
                 2.67 
                 1.46 
               
               
                 Stdev 
                 2.47 
                 2.38 
                 2.47 
                 2.56 
                 2.47 
                 1.95 
               
               
                 p(t-test) 
                   
                 0.73 
                   
                 0.21 
                   
                 0.046 
               
               
                 Min 
                 0.00152 
                 0.00181 
                 0.00152 
                 0.00212 
                 0.00152 
                 0.00546 
               
               
                 Max 
                 6.10 
                 6.10 
                 6.10 
                 6.10 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 421 
                 25 
                 421 
                 33 
                 421 
                 17 
               
               
                 n (Patient) 
                 165 
                 25 
                 165 
                 33 
                 165 
                 17 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 nd 
                 nd 
                 1.47 
                 3.95 
                 1.47 
                 0.763 
               
               
                 Average 
                 nd 
                 nd 
                 2.57 
                 3.27 
                 2.57 
                 1.33 
               
               
                 Stdev 
                 nd 
                 nd 
                 2.45 
                 2.75 
                 2.45 
                 1.42 
               
               
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.43 
                   
                 0.18 
               
               
                 Min 
                 nd 
                 nd 
                 0.00152 
                 0.0843 
                 0.00152 
                 0.0324 
               
               
                 Max 
                 nd 
                 nd 
                 6.10 
                 5.80 
                 6.10 
                 3.49 
               
               
                 n (Samp) 
                 nd 
                 nd 
                 511 
                 8 
                 511 
                 7 
               
               
                 n (Patient) 
                 nd 
                 nd 
                 198 
                 8 
                 198 
                 7 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 1.81 
                 3.29 
                 1.81 
                 0.721 
                 1.81 
                 0.261 
               
               
                 Average 
                 2.73 
                 2.89 
                 2.73 
                 1.92 
                 2.73 
                 1.84 
               
               
                 Stdev 
                 2.48 
                 2.35 
                 2.48 
                 2.38 
                 2.48 
                 2.40 
               
               
                 p(t-test) 
                   
                 0.74 
                   
                 0.093 
                   
                 0.15 
               
               
                 Min 
                 0.00152 
                 0.00181 
                 0.00152 
                 0.00212 
                 0.00152 
                 0.00546 
               
               
                 Max 
                 6.10 
                 6.10 
                 6.10 
                 6.10 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 357 
                 25 
                 357 
                 29 
                 357 
                 17 
               
               
                 n (Patient) 
                 135 
                 25 
                 135 
                 29 
                 135 
                 17 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.52 
                 nd 
                 0.51 
                 0.43 
                 0.57 
                 0.41 
                 0.33 
                 0.39 
                 0.35 
               
               
                 SE 
                 0.060 
                 nd 
                 0.060 
                 0.054 
                 0.11 
                 0.057 
                 0.073 
                 0.11 
                 0.074 
               
               
                 p 
                 0.75 
                 nd 
                 0.84 
                 0.21 
                 0.48 
                 0.11 
                 0.024 
                 0.35 
                 0.040 
               
               
                 nCohort 1 
                 421 
                 nd 
                 357 
                 421 
                 511 
                 357 
                 421 
                 511 
                 357 
               
               
                 nCohort 2 
                 25 
                 nd 
                 25 
                 33 
                 8 
                 29 
                 17 
                 7 
                 17 
               
               
                 Cutoff 1 
                 0.363 
                 nd 
                 0.363 
                 0.153 
                 0.518 
                 0.152 
                 0.107 
                 0.476 
                 0.107 
               
               
                 Sens 1 
                 72% 
                 nd 
                 72% 
                 73% 
                 75% 
                 72% 
                 71% 
                 71% 
                 71% 
               
               
                 Spec 1 
                 33% 
                 nd 
                 31% 
                 22% 
                 37% 
                 19% 
                 17% 
                 36% 
                 15% 
               
               
                 Cutoff 2 
                 0.278 
                 nd 
                 0.278 
                 0.0572 
                 0.200 
                 0.0497 
                 0.0376 
                 0.153 
                 0.0351 
               
               
                 Sens 2 
                 80% 
                 nd 
                 80% 
                 82% 
                 88% 
                 83% 
                 82% 
                 86% 
                 82% 
               
               
                 Spec 2 
                 29% 
                 nd 
                 27% 
                 10% 
                 26% 
                  9% 
                  7% 
                 23% 
                  7% 
               
               
                 Cutoff 3 
                 0.0351 
                 nd 
                 0.0351 
                 0.0319 
                 0.0830 
                 0.00312 
                 0.0124 
                 0.0319 
                 0.0124 
               
               
                 Sens 3 
                 92% 
                 nd 
                 92% 
                 91% 
                 100%  
                 93% 
                 94% 
                 100%  
                 94% 
               
               
                 Spec 3 
                  7% 
                 nd 
                  7% 
                  6% 
                 16% 
                  1% 
                  3% 
                  7% 
                  2% 
               
               
                 Cutoff 4 
                 5.48 
                 nd 
                 5.57 
                 5.48 
                 5.13 
                 5.57 
                 5.48 
                 5.13 
                 5.57 
               
               
                 Sens 4 
                 24% 
                 nd 
                 20% 
                 30% 
                 50% 
                 24% 
                  6% 
                  0% 
                 18% 
               
               
                 Spec 4 
                 70% 
                 nd 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 5.80 
                 nd 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
               
               
                 Sens 5 
                 12% 
                 nd 
                 12% 
                 6% 
                  0% 
                  7% 
                  0% 
                  0% 
                  0% 
               
               
                 Spec 5 
                 94% 
                 nd 
                 94% 
                 94% 
                 94% 
                 94% 
                 94% 
                 94% 
                 94% 
               
               
                 Cutoff 6 
                 5.80 
                 nd 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
               
               
                 Sens 6 
                 12% 
                 nd 
                 12% 
                  6% 
                  0% 
                  7% 
                  0% 
                  0% 
                  0% 
               
               
                 Spec 6 
                 94% 
                 nd 
                 94% 
                 94% 
                 94% 
                 94% 
                 94% 
                 94% 
                 94% 
               
               
                 OR Quart 2 
                 1.8 
                 nd 
                 0.99 
                 0.19 
                 2.0 
                 0.66 
                 4.2 
                 &gt;2.0 
                 2.1 
               
               
                 p Value 
                 0.37 
                 nd 
                 0.99 
                 0.033 
                 0.57 
                 0.53 
                 0.21 
                 &lt;0.56 
                 0.41 
               
               
                 95% CI of 
                 0.51 
                 nd 
                 0.28 
                 0.040 
                 0.18 
                 0.18 
                 0.46 
                 &gt;0.18 
                 0.37 
               
               
                 OR Quart2 
                 6.3 
                 nd 
                 3.5 
                 0.88 
                 22 
                 2.4 
                 38 
                 na 
                 12 
               
               
                 OR Quart 3 
                 2.6 
                 nd 
                 2.6 
                 0.89 
                 2.0 
                 1.4 
                 4.1 
                 &gt;3.1 
                 1.5 
               
               
                 p Value 
                 0.11 
                 nd 
                 0.084 
                 0.81 
                 0.57 
                 0.58 
                 0.21 
                 &lt;0.33 
                 0.65 
               
               
                 95% CI of 
                 0.80 
                 nd 
                 0.88 
                 0.35 
                 0.18 
                 0.45 
                 0.45 
                 &gt;0.32 
                 0.25 
               
               
                 OR Quart3 
                 8.7 
                 nd 
                 7.7 
                 2.3 
                 22 
                 4.1 
                 37 
                 na 
                 9.3 
               
               
                 OR Quart 4 
                 0.99 
                 nd 
                 0.58 
                 1.2 
                 3.0 
                 2.0 
                 8.6 
                 &gt;2.0 
                 4.3 
               
               
                 p Value 
                 0.99 
                 nd 
                 0.47 
                 0.64 
                 0.34 
                 0.20 
                 0.044 
                 &lt;0.56 
                 0.069 
               
               
                 95% CI of 
                 0.24 
                 nd 
                 0.13 
                 0.51 
                 0.31 
                 0.70 
                 1.1 
                 &gt;0.18 
                 0.89 
               
               
                 OR Quart4 
                 4.1 
                 nd 
                 2.5 
                 3.0 
                 29 
                 5.5 
                 70 
                 na 
                 21 
               
               
                   
               
            
           
           
               
            
               
                 C-X-C motif chemokine 2 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.485 
                 1.87 
                 0.485 
                 6.90 
                 0.485 
                 0.889 
               
               
                   
                 Average 
                 8.64 
                 16.6 
                 8.64 
                 23.6 
                 8.64 
                 5.37 
               
               
                   
                 Stdev 
                 24.6 
                 39.6 
                 24.6 
                 44.3 
                 24.6 
                 7.31 
               
               
                   
                 p(t-test) 
                   
                 0.066 
                   
                 1.4E−4 
                   
                 0.48 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 20.9 
               
               
                   
                 n (Samp) 
                 690 
                 37 
                 690 
                 48 
                 690 
                 28 
               
               
                   
                 n (Patient) 
                 279 
                 37 
                 279 
                 48 
                 279 
                 28 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.687 
                 11.6 
                 0.687 
                 15.2 
                 0.687 
                 3.34 
               
               
                   
                 Average 
                 8.64 
                 42.0 
                 8.64 
                 33.1 
                 8.64 
                 10.1 
               
               
                   
                 Stdev 
                 24.0 
                 69.5 
                 24.0 
                 58.6 
                 24.0 
                 12.5 
               
               
                   
                 p(t-test) 
                   
                 6.6E−5 
                   
                 4.4E−4 
                   
                 0.83 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 31.3 
               
               
                   
                 n (Samp) 
                 899 
                 9 
                 899 
                 13 
                 899 
                 13 
               
               
                   
                 n (Patient) 
                 335 
                 9 
                 335 
                 13 
                 335 
                 13 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.671 
                 1.65 
                 0.671 
                 6.97 
                 0.671 
                 2.64 
               
               
                   
                 Average 
                 9.13 
                 16.4 
                 9.13 
                 25.2 
                 9.13 
                 5.99 
               
               
                   
                 Stdev 
                 24.9 
                 40.7 
                 24.9 
                 46.4 
                 24.9 
                 7.43 
               
               
                   
                 p(t-test) 
                   
                 0.11 
                   
                 1.7E−4 
                   
                 0.53 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 20.9 
               
               
                   
                 n (Samp) 
                 578 
                 35 
                 578 
                 43 
                 578 
                 25 
               
               
                   
                 n (Patient) 
                 205 
                 35 
                 205 
                 43 
                 205 
                 25 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.72 
                 0.55 
                 0.68 
                 0.73 
                 0.68 
                 0.52 
                 0.58 
                 0.55 
               
               
                 SE 
                 0.050 
                 0.097 
                 0.051 
                 0.044 
                 0.080 
                 0.046 
                 0.056 
                 0.083 
                 0.060 
               
               
                 p 
                 0.12 
                 0.025 
                 0.35 
                 3.3E−5 
                 0.0045 
                 1.1E−4 
                 0.73 
                 0.34 
                 0.38 
               
               
                 nCohort 1 
                 690 
                 899 
                 578 
                 690 
                 899 
                 578 
                 690 
                 899 
                 578 
               
               
                 nCohort 2 
                 37 
                 9 
                 35 
                 48 
                 13 
                 43 
                 28 
                 13 
                 25 
               
               
                 Cutoff 1 
                 0.00804 
                 1.86 
                 0.00804 
                 1.45 
                 5.86 
                 1.45 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                 Sens 1 
                 100%  
                 78% 
                 100%  
                 71% 
                 77% 
                 72% 
                 100%  
                 100%  
                 100%  
               
               
                 Spec 1 
                  0% 
                 57% 
                  0% 
                 57% 
                 73% 
                 54% 
                  0% 
                  0% 
                  0% 
               
               
                 Cutoff 2 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.121 
                 0.00804 
                 0.299 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                 Sens 2 
                 100%  
                 100%  
                 100%  
                 81% 
                 100%  
                 81% 
                 100%  
                 100%  
                 100%  
               
               
                 Spec 2 
                  0% 
                  0% 
                  0% 
                 45% 
                  0% 
                 46% 
                  0% 
                  0% 
                  0% 
               
               
                 Cutoff 3 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                 Sens 3 
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
                 100%  
               
               
                 Spec 3 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
               
               
                 Cutoff 4 
                 4.12 
                 4.66 
                 4.76 
                 4.12 
                 4.66 
                 4.76 
                 4.12 
                 4.66 
                 4.76 
               
               
                 Sens 4 
                 38% 
                 67% 
                 34% 
                 56% 
                 77% 
                 56% 
                 36% 
                 46% 
                 40% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 8.05 
                 8.68 
                 8.50 
                 8.05 
                 8.68 
                 8.50 
                 8.05 
                 8.68 
                 8.50 
               
               
                 Sens 5 
                 32% 
                 56% 
                 29% 
                 48% 
                 62% 
                 49% 
                 29% 
                 46% 
                 28% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 19.6 
                 19.7 
                 21.7 
                 19.6 
                 19.7 
                 21.7 
                 19.6 
                 19.7 
                 21.7 
               
               
                 Sens 6 
                 16% 
                 44% 
                 14% 
                 31% 
                 46% 
                 30% 
                  4% 
                 23% 
                  0% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.16 
                 0 
                 &gt;15 
                 &gt;14 
                 0 
                 &gt;12 
                 0.16 
                 0 
                 0.24 
               
               
                 p Value 
                 0.016 
                 na 
                 &lt;0.0087 
                 &lt;0.012 
                 na 
                 &lt;0.019 
                 0.016 
                 na 
                 0.073 
               
               
                 95% CI of 
                 0.035 
                 na 
                 &gt;2.0 
                 &gt;1.8 
                 na 
                 &gt;1.5 
                 0.034 
                 na 
                 0.050 
               
               
                 OR Quart2 
                 0.71 
                 na 
                 na 
                 na 
                 na 
                 na 
                 0.71 
                 na 
                 1.1 
               
               
                 OR Quart 3 
                 0.82 
                 0.50 
                 &gt;11 
                 &gt;11 
                 0.66 
                 &gt;12 
                 0.48 
                 0.39 
                 0.99 
               
               
                 p Value 
                 0.65 
                 0.57 
                 &lt;0.025 
                 &lt;0.025 
                 0.66 
                 &lt;0.019 
                 0.15 
                 0.27 
                 0.99 
               
               
                 95% CI of 
                 0.34 
                 0.045 
                 &gt;1.4 
                 &gt;1.3 
                 0.11 
                 &gt;1.5 
                 0.18 
                 0.076 
                 0.36 
               
               
                 OR Quart3 
                 1.9 
                 5.5 
                 na 
                 na 
                 4.0 
                 na 
                 1.3 
                 2.1 
                 2.7 
               
               
                 OR Quart 4 
                 1.1 
                 3.1 
                 &gt;12 
                 &gt;29 
                 2.7 
                 &gt;24 
                 0.65 
                 1.2 
                 0.86 
               
               
                 p Value 
                 0.85 
                 0.17 
                 &lt;0.019 
                 &lt;0.0011 
                 0.14 
                 &lt;0.0020 
                 0.35 
                 0.76 
                 0.78 
               
               
                 95% CI of 
                 0.48 
                 0.61 
                 &gt;1.5 
                 &gt;3.9 
                 0.71 
                 &gt;3.2 
                 0.26 
                 0.36 
                 0.30 
               
               
                 OR Quart4 
                 2.4 
                 15 
                 na 
                 na 
                 10 
                 na 
                 1.6 
                 4.0 
                 2.4 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 343 
                 669 
                 343 
                 1180 
                 343 
                 380 
               
               
                   
                 Average 
                 808 
                 1130 
                 808 
                 2210 
                 808 
                 1220 
               
               
                   
                 Stdev 
                 1290 
                 1140 
                 1290 
                 3740 
                 1290 
                 1780 
               
               
                   
                 p(t-test) 
                   
                 0.25 
                   
                 3.1E−5  
                   
                 0.23 
               
               
                   
                 Min 
                 1.00E−9 
                 18.7 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 9810 
                 4050 
                 9810 
                 21100 
                 9810 
                 5550 
               
               
                   
                 n (Samp) 
                 239 
                 22 
                 239 
                 32 
                 239 
                 16 
               
               
                   
                 n (Patient) 
                 157 
                 22 
                 157 
                 32 
                 157 
                 16 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 nd 
                 nd 
                 394 
                 1010 
                 394 
                 2150 
               
               
                   
                 Average 
                 nd 
                 nd 
                 954 
                 1350 
                 954 
                 2600 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 1740 
                 1410 
                 1740 
                 2150 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.58 
                   
                 0.014 
               
               
                   
                 Min 
                 nd 
                 nd 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 nd 
                 nd 
                 21100 
                 3390 
                 21100 
                 5380 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 305 
                 6 
                 305 
                 7 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 184 
                 6 
                 184 
                 7 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 346 
                 699 
                 346 
                 1180 
                 346 
                 435 
               
               
                   
                 Average 
                 847 
                 1160 
                 847 
                 2270 
                 847 
                 1220 
               
               
                   
                 Stdev 
                 1350 
                 1120 
                 1350 
                 3900 
                 1350 
                 1790 
               
               
                   
                 p(t-test) 
                   
                 0.30 
                   
                 1.3E−4  
                   
                 0.31 
               
               
                   
                 Min 
                 1.00E−9 
                 18.7 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 9810 
                 4050 
                 9810 
                 21100 
                 9810 
                 5550 
               
               
                   
                 n (Samp) 
                 207 
                 22 
                 207 
                 29 
                 207 
                 15 
               
               
                   
                 n (Patient) 
                 130 
                 22 
                 130 
                 29 
                 130 
                 15 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.64 
                 nd 
                 0.64 
                 0.70 
                 0.58 
                 0.71 
                 0.52 
                 0.68 
                 0.54 
               
               
                 SE 
                 0.066 
                 nd 
                 0.066 
                 0.054 
                 0.12 
                 0.057 
                 0.075 
                 0.11 
                 0.079 
               
               
                 p 
                 0.033 
                 nd 
                 0.030 
                 1.6E−4 
                 0.50 
                 2.3E−4 
                 0.82 
                 0.10 
                 0.63 
               
               
                 nCohort 1 
                 239 
                 nd 
                 207 
                 239 
                 305 
                 207 
                 239 
                 305 
                 207 
               
               
                 nCohort 2 
                 22 
                 nd 
                 22 
                 32 
                 6 
                 29 
                 16 
                 7 
                 15 
               
               
                 Cutoff 1 
                 337 
                 nd 
                 397 
                 453 
                 38.3 
                 397 
                 88.6 
                 2070 
                 134 
               
               
                 Sens 1 
                 73% 
                 nd 
                 73% 
                 72% 
                 83% 
                 72% 
                 75% 
                 71% 
                 73% 
               
               
                 Spec 1 
                 50% 
                 nd 
                 55% 
                 57% 
                 16% 
                 55% 
                 24% 
                 88% 
                 28% 
               
               
                 Cutoff 2 
                 266 
                 nd 
                 266 
                 380 
                 38.3 
                 310 
                 69.5 
                 0 
                 118 
               
               
                 Sens 2 
                 82% 
                 nd 
                 82% 
                 81% 
                 83% 
                 83% 
                 81% 
                 100%  
                 80% 
               
               
                 Spec 2 
                 44% 
                 nd 
                 43% 
                 52% 
                 16% 
                 48% 
                 23% 
                  0% 
                 25% 
               
               
                 Cutoff 3 
                 69.5 
                 nd 
                 69.5 
                 96.1 
                 0 
                 125 
                 0 
                 0 
                 69.5 
               
               
                 Sens 3 
                 91% 
                 nd 
                 91% 
                 91% 
                 100%  
                 93% 
                 100%  
                 100%  
                 93% 
               
               
                 Spec 3 
                 23% 
                 nd 
                 21% 
                 25% 
                  0% 
                 26% 
                  0% 
                  0% 
                 21% 
               
               
                 Cutoff 4 
                 730 
                 nd 
                 743 
                 730 
                 879 
                 743 
                 730 
                 879 
                 743 
               
               
                 Sens 4 
                 45% 
                 nd 
                 45% 
                 66% 
                 50% 
                 66% 
                 38% 
                 71% 
                 33% 
               
               
                 Spec 4 
                 70% 
                 nd 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 1280 
                 nd 
                 1410 
                 1280 
                 1590 
                 1410 
                 1280 
                 1590 
                 1410 
               
               
                 Sens 5 
                 32% 
                 nd 
                 32% 
                 47% 
                 33% 
                 45% 
                 38% 
                 71% 
                 27% 
               
               
                 Spec 5 
                 80% 
                 nd 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 2070 
                 nd 
                 2140 
                 2070 
                 2390 
                 2140 
                 2070 
                 2390 
                 2140 
               
               
                 Sens 6 
                 18% 
                 nd 
                 18% 
                 38% 
                 33% 
                 38% 
                 19% 
                 43% 
                 13% 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 1.4 
                 nd 
                 1.0 
                 0.73 
                 0 
                 1.4 
                 0.57 
                 0 
                 1.3 
               
               
                 p Value 
                 0.70 
                 nd 
                 1.0 
                 0.68 
                 na 
                 0.70 
                 0.46 
                 na 
                 0.72 
               
               
                 95% CI of 
                 0.29 
                 nd 
                 0.19 
                 0.16 
                 na 
                 0.29 
                 0.13 
                 na 
                 0.28 
               
               
                 OR Quart2 
                 6.3 
                 nd 
                 5.2 
                 3.4 
                 na 
                 6.3 
                 2.5 
                 na 
                 6.3 
               
               
                 OR Quart 3 
                 2.5 
                 nd 
                 2.9 
                 2.1 
                 0.49 
                 3.4 
                 0.37 
                 0 
                 1.0 
               
               
                 p Value 
                 0.20 
                 nd 
                 0.13 
                 0.25 
                 0.56 
                 0.081 
                 0.25 
                 na 
                 1.0 
               
               
                 95% CI of 
                 0.62 
                 nd 
                 0.74 
                 0.60 
                 0.043 
                 0.86 
                 0.070 
                 na 
                 0.19 
               
               
                 OR Quart3 
                 10 
                 nd 
                 12 
                 7.3 
                 5.5 
                 13 
                 2.0 
                 na 
                 5.2 
               
               
                 OR Quart 4 
                 2.9 
                 nd 
                 2.9 
                 5.2 
                 1.5 
                 5.3 
                 1.2 
                 2.6 
                 1.7 
               
               
                 p Value 
                 0.14 
                 nd 
                 0.13 
                 0.0047 
                 0.66 
                 0.013 
                 0.77 
                 0.26 
                 0.48 
               
               
                 95% CI of 
                 0.72 
                 nd 
                 0.72 
                 1.7 
                 0.24 
                 1.4 
                 0.35 
                 0.49 
                 0.39 
               
               
                 OR Quart4 
                 11 
                 nd 
                 11 
                 17 
                 9.2 
                 20 
                 4.2 
                 14 
                 7.5 
               
               
                   
               
            
           
           
               
            
               
                 Cathepsin B 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.661 
                 0.911 
                 0.661 
                 1.10 
                 0.661 
                 0.312 
               
               
                   
                 Average 
                 2.94 
                 1.16 
                 2.94 
                 5.27 
                 2.94 
                 1.34 
               
               
                   
                 Stdev 
                 9.10 
                 1.30 
                 9.10 
                 12.7 
                 9.10 
                 1.86 
               
               
                   
                 p(t-test) 
                   
                 0.36 
                   
                 0.19 
                   
                 0.48 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 78.1 
                 5.47 
                 78.1 
                 64.9 
                 78.1 
                 4.98 
               
               
                   
                 n (Samp) 
                 256 
                 22 
                 256 
                 32 
                 256 
                 16 
               
               
                   
                 n (Patient) 
                 163 
                 22 
                 163 
                 32 
                 163 
                 16 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 nd 
                 nd 
                 0.648 
                 1.62 
                 0.648 
                 2.27 
               
               
                   
                 Average 
                 nd 
                 nd 
                 2.81 
                 6.92 
                 2.81 
                 5.45 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 8.88 
                 9.65 
                 8.88 
                 10.8 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.26 
                   
                 0.44 
               
               
                   
                 Min 
                 nd 
                 nd 
                 1.00E−9 
                 0.593 
                 1.00E−9 
                 0.0682 
               
               
                   
                 Max 
                 nd 
                 nd 
                 78.1 
                 24.2 
                 78.1 
                 29.7 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 322 
                 6 
                 322 
                 7 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 190 
                 6 
                 190 
                 7 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.768 
                 0.911 
                 0.768 
                 1.20 
                 0.768 
                 0.605 
               
               
                   
                 Average 
                 3.26 
                 1.14 
                 3.26 
                 5.03 
                 3.26 
                 2.90 
               
               
                   
                 Stdev 
                 9.69 
                 1.27 
                 9.69 
                 12.8 
                 9.69 
                 6.17 
               
               
                   
                 p(t-test) 
                   
                 0.31 
                   
                 0.38 
                   
                 0.89 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
               
               
                   
                 Max 
                 78.1 
                 5.29 
                 78.1 
                 64.9 
                 78.1 
                 24.2 
               
               
                   
                 n (Samp) 
                 222 
                 22 
                 222 
                 29 
                 222 
                 15 
               
               
                   
                 n (Patient) 
                 135 
                 22 
                 135 
                 29 
                 135 
                 15 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.50 
                 nd 
                 0.47 
                 0.62 
                 0.73 
                 0.59 
                 0.42 
                 0.60 
                 0.44 
               
               
                 SE 
                 0.064 
                 nd 
                 0.066 
                 0.056 
                 0.12 
                 0.059 
                 0.077 
                 0.11 
                 0.079 
               
               
                 p 
                 0.96 
                 nd 
                 0.62 
                 0.032 
                 0.056 
                 0.14 
                 0.30 
                 0.37 
                 0.46 
               
               
                 nCohort 1 
                 256 
                 nd 
                 222 
                 256 
                 322 
                 222 
                 256 
                 322 
                 222 
               
               
                 nCohort 2 
                 22 
                 nd 
                 22 
                 32 
                 6 
                 29 
                 16 
                 7 
                 15 
               
               
                 Cutoff 1 
                 0.296 
                 nd 
                 0.296 
                 0.572 
                 0.797 
                 0.522 
                 0.0513 
                 0.319 
                 0.158 
               
               
                 Sens 1 
                 73% 
                 nd 
                 73% 
                 72% 
                 83% 
                 72% 
                 75% 
                 71% 
                 73% 
               
               
                 Spec 1 
                 32% 
                 nd 
                 29% 
                 48% 
                 55% 
                 39% 
                 13% 
                 34% 
                 18% 
               
               
                 Cutoff 2 
                 0.140 
                 nd 
                 0.140 
                 0.463 
                 0.797 
                 0.460 
                 0 
                 0.309 
                 0 
               
               
                 Sens 2 
                 82% 
                 nd 
                 82% 
                 81% 
                 83% 
                 83% 
                 100%  
                 86% 
                 100%  
               
               
                 Spec 2 
                 19% 
                 nd 
                 17% 
                 40% 
                 55% 
                 35% 
                  0% 
                 33% 
                  0% 
               
               
                 Cutoff 3 
                 1.00E−9 
                 nd 
                 1.00E−9 
                 0.290 
                 0.572 
                 0.236 
                 0 
                 0.0513 
                 0 
               
               
                 Sens 3 
                 91% 
                 nd 
                 91% 
                 91% 
                 100%  
                 93% 
                 100%  
                 100%  
                 100%  
               
               
                 Spec 3 
                 12% 
                 nd 
                 10% 
                 31% 
                 48% 
                 23% 
                  0% 
                 14% 
                  0% 
               
               
                 Cutoff 4 
                 1.46 
                 nd 
                 1.64 
                 1.46 
                 1.41 
                 1.64 
                 1.46 
                 1.41 
                 1.64 
               
               
                 Sens 4 
                 27% 
                 nd 
                 23% 
                 38% 
                 50% 
                 38% 
                 31% 
                 57% 
                 33% 
               
               
                 Spec 4 
                 70% 
                 nd 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 2.37 
                 nd 
                 2.74 
                 2.37 
                 2.37 
                 2.74 
                 2.37 
                 2.37 
                 2.74 
               
               
                 Sens 5 
                 14% 
                 nd 
                  9% 
                 25% 
                 33% 
                 28% 
                 25% 
                 43% 
                 27% 
               
               
                 Spec 5 
                 80% 
                 nd 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 5.61 
                 nd 
                 6.20 
                 5.61 
                 4.86 
                 6.20 
                 5.61 
                 4.86 
                 6.20 
               
               
                 Sens 6 
                  0% 
                 nd 
                  0% 
                 16% 
                 33% 
                 14% 
                  0% 
                 14% 
                  7% 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 1.7 
                 nd 
                 3.3 
                 2.9 
                 &gt;1.0 
                 2.9 
                 0.19 
                 2.0 
                 0 
               
               
                 p Value 
                 0.37 
                 nd 
                 0.082 
                 0.13 
                 &lt;0.99 
                 0.13 
                 0.13 
                 0.57 
                 na 
               
               
                 95% CI of 
                 0.53 
                 nd 
                 0.86 
                 0.73 
                 &gt;0.062 
                 0.72 
                 0.021 
                 0.18 
                 na 
               
               
                 OR Quart2 
                 5.5 
                 nd 
                 13 
                 11 
                 na 
                 11 
                 1.7 
                 23 
                 na 
               
               
                 OR Quart 3 
                 0.79 
                 nd 
                 1.7 
                 3.7 
                 &gt;2.0 
                 2.9 
                 0.79 
                 0 
                 0.80 
               
               
                 p Value 
                 0.73 
                 nd 
                 0.47 
                 0.054 
                 &lt;0.56 
                 0.13 
                 0.73 
                 na 
                 0.75 
               
               
                 95% CI of 
                 0.20 
                 nd 
                 0.39 
                 0.98 
                 &gt;0.18 
                 0.72 
                 0.20 
                 na 
                 0.20 
               
               
                 OR Quart3 
                 3.1 
                 nd 
                 7.6 
                 14 
                 na 
                 11 
                 3.1 
                 na 
                 3.1 
               
               
                 OR Quart 4 
                 1.0 
                 nd 
                 1.7 
                 4.1 
                 &gt;3.1 
                 3.7 
                 1.2 
                 4.1 
                 1.2 
               
               
                 p Value 
                 0.98 
                 nd 
                 0.47 
                 0.035 
                 &lt;0.33 
                 0.056 
                 0.75 
                 0.21 
                 0.73 
               
               
                 95% CI of 
                 0.28 
                 nd 
                 0.39 
                 1.1 
                 &gt;0.32 
                 0.97 
                 0.35 
                 0.45 
                 0.36 
               
               
                 OR Quart4 
                 3.7 
                 nd 
                 7.6 
                 16 
                 na 
                 14 
                 4.2 
                 38 
                 4.3 
               
               
                   
               
            
           
           
               
            
               
                 Dipeptidyl peptidase IV 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 157 
                 473 
                 157 
                 662 
                 157 
                 455 
               
               
                 Average 
                 4080 
                 1160 
                 4080 
                 1750 
                 4080 
                 758 
               
               
                 Stdev 
                 47500 
                 1640 
                 47500 
                 3170 
                 47500 
                 826 
               
               
                 p(t-test) 
                   
                 0.81 
                   
                 0.83 
                   
                 0.82 
               
               
                 Min 
                 0.200 
                 7.95 
                 0.200 
                 10.1 
                 0.200 
                 17.0 
               
               
                 Max 
                 677000 
                 5420 
                 677000 
                 12500 
                 677000 
                 2280 
               
               
                 n (Samp) 
                 203 
                 16 
                 203 
                 19 
                 203 
                 11 
               
               
                 n (Patient) 
                 135 
                 16 
                 135 
                 19 
                 135 
                 11 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 151 
                 603 
                 151 
                 639 
                 151 
                 556 
               
               
                 Average 
                 619 
                 1230 
                 619 
                 1480 
                 619 
                 836 
               
               
                 Stdev 
                 1350 
                 1630 
                 1350 
                 2970 
                 1350 
                 777 
               
               
                 p(t-test) 
                   
                 0.091 
                   
                 0.028 
                   
                 0.60 
               
               
                 Min 
                 0.200 
                 7.95 
                 0.200 
                 10.1 
                 0.200 
                 17.0 
               
               
                 Max 
                 11000 
                 5420 
                 11000 
                 12500 
                 11000 
                 2280 
               
               
                 n (Samp) 
                 174 
                 16 
                 174 
                 18 
                 174 
                 11 
               
               
                 n (Patient) 
                 114 
                 16 
                 114 
                 18 
                 114 
                 11 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.61 
                 nd 
                 0.63 
                 0.66 
                 nd 
                 0.65 
                 0.61 
                 nd 
                 0.68 
               
               
                 SE 
                 0.077 
                 nd 
                 0.078 
                 0.071 
                 nd 
                 0.073 
                 0.093 
                 nd 
                 0.092 
               
               
                 p 
                 0.14 
                 nd 
                 0.086 
                 0.028 
                 nd 
                 0.039 
                 0.24 
                 nd 
                 0.055 
               
               
                 nCohort 1 
                 203 
                 nd 
                 174 
                 203 
                 nd 
                 174 
                 203 
                 nd 
                 174 
               
               
                 nCohort 2 
                 16 
                 nd 
                 16 
                 19 
                 nd 
                 18 
                 11 
                 nd 
                 11 
               
               
                 Cutoff 1 
                 63.4 
                 nd 
                 52.3 
                 294 
                 nd 
                 294 
                 161 
                 nd 
                 407 
               
               
                 Sens 1 
                 75% 
                 nd 
                 75% 
                 74% 
                 nd 
                 72% 
                 73% 
                 nd 
                 73% 
               
               
                 Spec 1 
                 33% 
                 nd 
                 32% 
                 60% 
                 nd 
                 61% 
                 51% 
                 nd 
                 65% 
               
               
                 Cutoff 2 
                 52.3 
                 nd 
                 31.7 
                 48.0 
                 nd 
                 48.0 
                 52.3 
                 nd 
                 161 
               
               
                 Sens 2 
                 81% 
                 nd 
                 81% 
                 84% 
                 nd 
                 83% 
                 82% 
                 nd 
                 82% 
               
               
                 Spec 2 
                 31% 
                 nd 
                 25% 
                 29% 
                 nd 
                 29% 
                 31% 
                 nd 
                 52% 
               
               
                 Cutoff 3 
                 18.2 
                 nd 
                 18.2 
                 18.2 
                 nd 
                 18.2 
                 39.0 
                 nd 
                 39.0 
               
               
                 Sens 3 
                 94% 
                 nd 
                 94% 
                 95% 
                 nd 
                 94% 
                 91% 
                 nd 
                 91% 
               
               
                 Spec 3 
                 19% 
                 nd 
                 20% 
                 19% 
                 nd 
                 20% 
                 27% 
                 nd 
                 27% 
               
               
                 Cutoff 4 
                 560 
                 nd 
                 529 
                 560 
                 nd 
                 529 
                 560 
                 nd 
                 529 
               
               
                 Sens 4 
                 44% 
                 nd 
                 50% 
                 58% 
                 nd 
                 61% 
                 36% 
                 nd 
                 55% 
               
               
                 Spec 4 
                 70% 
                 nd 
                 70% 
                 70% 
                 nd 
                 70% 
                 70% 
                 nd 
                 70% 
               
               
                 Cutoff 5 
                 1010 
                 nd 
                 889 
                 1010 
                 nd 
                 889 
                 1010 
                 nd 
                 889 
               
               
                 Sens 5 
                 25% 
                 nd 
                 31% 
                 26% 
                 nd 
                 33% 
                 36% 
                 nd 
                 36% 
               
               
                 Spec 5 
                 80% 
                 nd 
                 80% 
                 80% 
                 nd 
                 80% 
                 80% 
                 nd 
                 80% 
               
               
                 Cutoff 6 
                 1560 
                 nd 
                 1530 
                 1560 
                 nd 
                 1530 
                 1560 
                 nd 
                 1530 
               
               
                 Sens 6 
                 25% 
                 nd 
                 31% 
                 16% 
                 nd 
                 11% 
                 18% 
                 nd 
                 18% 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 90% 
               
               
                 OR Quart 2 
                 0.64 
                 nd 
                 0.64 
                 0.64 
                 nd 
                 0.65 
                 3.1 
                 nd 
                 1.0 
               
               
                 p Value 
                 0.63 
                 nd 
                 0.63 
                 0.63 
                 nd 
                 0.65 
                 0.34 
                 nd 
                 1.0 
               
               
                 95% CI of 
                 0.10 
                 nd 
                 0.10 
                 0.10 
                 nd 
                 0.10 
                 0.31 
                 nd 
                 0.061 
               
               
                 OR Quart2 
                 4.0 
                 nd 
                 4.0 
                 4.0 
                 nd 
                 4.1 
                 30 
                 nd 
                 16 
               
               
                 OR Quart 3 
                 2.1 
                 nd 
                 1.4 
                 2.5 
                 nd 
                 1.7 
                 3.1 
                 nd 
                 4.3 
               
               
                 p Value 
                 0.32 
                 nd 
                 0.70 
                 0.20 
                 nd 
                 0.46 
                 0.33 
                 nd 
                 0.20 
               
               
                 95% CI of 
                 0.49 
                 nd 
                 0.29 
                 0.62 
                 nd 
                 0.39 
                 0.31 
                 nd 
                 0.46 
               
               
                 OR Quart3 
                 8.8 
                 nd 
                 6.5 
                 10 
                 nd 
                 7.7 
                 31 
                 nd 
                 40 
               
               
                 OR Quart 4 
                 1.7 
                 nd 
                 2.5 
                 2.5 
                 nd 
                 3.0 
                 4.2 
                 nd 
                 5.4 
               
               
                 p Value 
                 0.48 
                 nd 
                 0.20 
                 0.21 
                 nd 
                 0.12 
                 0.21 
                 nd 
                 0.13 
               
               
                 95% CI of 
                 0.39 
                 nd 
                 0.61 
                 0.61 
                 nd 
                 0.74 
                 0.45 
                 nd 
                 0.60 
               
               
                 OR Quart4 
                 7.5 
                 nd 
                 10 
                 10 
                 nd 
                 12 
                 39 
                 nd 
                 48 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 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. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 4.78 
                 2.99 
                 4.78 
                 3.49 
                 4.78 
                 2.99 
               
               
                 Average 
                 3.59 
                 2.92 
                 3.59 
                 3.09 
                 3.59 
                 2.83 
               
               
                 Stdev 
                 2.43 
                 2.66 
                 2.43 
                 2.64 
                 2.43 
                 2.50 
               
               
                 p(t-test) 
                   
                 0.31 
                   
                 0.46 
                   
                 0.40 
               
               
                 Min 
                 0.00270 
                 0.00133 
                 0.00270 
                 0.00133 
                 0.00270 
                 0.0324 
               
               
                 Max 
                 6.10 
                 5.80 
                 6.10 
                 5.80 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 103 
                 16 
                 103 
                 15 
                 103 
                 8 
               
               
                 n (Patient) 
                 103 
                 16 
                 103 
                 15 
                 103 
                 8 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 4.50 
                 5.24 
                 4.50 
                 5.16 
                 nd 
                 nd 
               
               
                 Average 
                 3.52 
                 3.82 
                 3.52 
                 3.80 
                 nd 
                 nd 
               
               
                 Stdev 
                 2.47 
                 2.57 
                 2.47 
                 2.55 
                 nd 
                 nd 
               
               
                 p(t-test) 
                   
                 0.74 
                   
                 0.75 
                 nd 
                 nd 
               
               
                 Min 
                 0.00270 
                 0.00133 
                 0.00270 
                 0.00133 
                 nd 
                 nd 
               
               
                 Max 
                 6.10 
                 5.80 
                 6.10 
                 5.80 
                 nd 
                 nd 
               
               
                 n (Samp) 
                 170 
                 8 
                 170 
                 8 
                 nd 
                 nd 
               
               
                 n (Patient) 
                 170 
                 8 
                 170 
                 8 
                 nd 
                 nd 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 4.20 
                 0.348 
                 4.20 
                 0.480 
                 4.20 
                 1.83 
               
               
                 Average 
                 3.52 
                 2.21 
                 3.52 
                 2.43 
                 3.52 
                 2.57 
               
               
                 Stdev 
                 2.42 
                 2.68 
                 2.42 
                 2.74 
                 2.42 
                 2.82 
               
               
                 p(t-test) 
                   
                 0.11 
                   
                 0.21 
                   
                 0.36 
               
               
                 Min 
                 0.00270 
                 0.0324 
                 0.00270 
                 0.0324 
                 0.00270 
                 0.0324 
               
               
                 Max 
                 6.10 
                 5.80 
                 6.10 
                 5.80 
                 6.10 
                 5.80 
               
               
                 n (Samp) 
                 87 
                 10 
                 87 
                 9 
                 87 
                 6 
               
               
                 n (Patient) 
                 87 
                 10 
                 87 
                 9 
                 87 
                 6 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.41 
                 0.49 
                 0.32 
                 0.41 
                 0.47 
                 0.35 
                 0.38 
                 nd 
                 0.36 
               
               
                 SE 
                 0.080 
                 0.11 
                 0.098 
                 0.082 
                 0.11 
                 0.10 
                 0.11 
                 nd 
                 0.13 
               
               
                 p 
                 0.24 
                 0.95 
                 0.073 
                 0.29 
                 0.81 
                 0.14 
                 0.28 
                 nd 
                 0.25 
               
               
                 nCohort 1 
                 103 
                 170 
                 87 
                 103 
                 170 
                 87 
                 103 
                 nd 
                 87 
               
               
                 nCohort 2 
                 16 
                 8 
                 10 
                 15 
                 8 
                 9 
                 8 
                 nd 
                 6 
               
               
                 Cutoff 1 
                 0.170 
                 2.39 
                 0.170 
                 0.170 
                 2.39 
                 0.152 
                 0.170 
                 nd 
                 0.0851 
               
               
                 Sens 1 
                 75% 
                 75% 
                 70% 
                 73% 
                 75% 
                 78%  
                 75% 
                 nd 
                 83%  
               
               
                 Spec 1 
                 13% 
                 38% 
                 10% 
                 13% 
                 38% 
                 9% 
                 13% 
                 nd 
                 9% 
               
               
                 Cutoff 2 
                 0.152 
                 0.152 
                 0.152 
                 0.152 
                 0.152 
                 0.0851 
                 0.0851 
                 nd 
                 0.0851 
               
               
                 Sens 2 
                 81% 
                 88% 
                 80% 
                 80% 
                 88% 
                 89%  
                 88% 
                 nd 
                 83%  
               
               
                 Spec 2 
                 12% 
                 13% 
                  9% 
                 12% 
                 13% 
                 9% 
                 12% 
                 nd 
                 9% 
               
               
                 Cutoff 3 
                 0.0319 
                 0 
                 0.0851 
                 0.0319 
                 0 
                 0.0273 
                 0.0319 
                 nd 
                 0.0273 
               
               
                 Sens 3 
                 94% 
                 100%  
                 90% 
                 93% 
                 100%  
                 100%  
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                  6% 
                  0% 
                  9% 
                  6% 
                  0% 
                 5% 
                  6% 
                 nd 
                 5% 
               
               
                 Cutoff 4 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 nd 
                 5.80 
               
               
                 Sens 4 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                 0% 
                  0% 
                 nd 
                 0% 
               
               
                 Spec 4 
                 89% 
                 88% 
                 86% 
                 89% 
                 88% 
                 86%  
                 89% 
                 nd 
                 86%  
               
               
                 Cutoff 5 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 5.80 
                 nd 
                 5.80 
               
               
                 Sens 5 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                 0% 
                  0% 
                 nd 
                 0% 
               
               
                 Spec 5 
                 89% 
                 88% 
                 86% 
                 89% 
                 88% 
                 86%  
                 89% 
                 nd 
                 86%  
               
               
                 Cutoff 6 
                 5.84 
                 6.10 
                 6.10 
                 5.84 
                 6.10 
                 6.10 
                 5.84 
                 nd 
                 6.10 
               
               
                 Sens 6 
                  0% 
                  0% 
                  0% 
                  0% 
                  0% 
                 0% 
                  0% 
                 nd 
                 0% 
               
               
                 Spec 6 
                 90% 
                 100%  
                 100%  
                 90% 
                 100%  
                 100%  
                 90% 
                 nd 
                 100%  
               
               
                 OR Quart 2 
                 &gt;9.1 
                 &gt;5.8 
                 &gt;3.6 
                 &gt;9.5 
                 &gt;5.8 
                 &gt;3.4 
                 &gt;3.4 
                 nd 
                 1.0 
               
               
                 p Value 
                 &lt;0.045 
                 &lt;0.12 
                 &lt;0.29 
                 &lt;0.041 
                 &lt;0.12 
                 &lt;0.30 
                 &lt;0.31 
                 nd 
                 0.98 
               
               
                 95% CI of 
                 &gt;1.0 
                 &gt;0.65 
                 &gt;0.35 
                 &gt;1.1 
                 &gt;0.65 
                 &gt;0.33 
                 &gt;0.33 
                 nd 
                 0.062 
               
               
                 OR Quart2 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 18 
               
               
                 OR Quart 3 
                 &gt;2.1 
                 &gt;1.0 
                 &gt;1.1 
                 &gt;2.1 
                 &gt;1.0 
                 &gt;1.0 
                 &gt;2.2 
                 nd 
                 1.0 
               
               
                 p Value 
                 &lt;0.54 
                 &lt;0.99 
                 &lt;0.95 
                 &lt;0.54 
                 &lt;0.99 
                 &lt;0.98 
                 &lt;0.54 
                 nd 
                 0.98 
               
               
                 95% CI of 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.064 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.062 
                 &gt;0.18 
                 nd 
                 0.062 
               
               
                 OR Quart3 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 18 
               
               
                 OR Quart 4 
                 &gt;9.5 
                 &gt;2.1 
                 &gt;8.3 
                 &gt;7.8 
                 &gt;2.1 
                 &gt;6.3 
                 &gt;3.5 
                 nd 
                 3.4 
               
               
                 p Value 
                 &lt;0.041 
                 &lt;0.54 
                 &lt;0.059 
                 &lt;0.065 
                 &lt;0.54 
                 &lt;0.11 
                 &lt;0.29 
                 nd 
                 0.30 
               
               
                 95% CI of 
                 &gt;1.1 
                 &gt;0.19 
                 &gt;0.92 
                 &gt;0.88 
                 &gt;0.19 
                 &gt;0.68 
                 &gt;0.34 
                 nd 
                 0.33 
               
               
                 OR Quart4 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 36 
               
               
                   
               
            
           
           
               
            
               
                 C-X-C motif chemokine 2 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 1.04 
                 28.7 
                 1.04 
                 27.8 
                 1.04 
                 3.34 
               
               
                   
                 Average 
                 9.16 
                 42.4 
                 9.16 
                 37.7 
                 9.16 
                 12.4 
               
               
                   
                 Stdev 
                 30.2 
                 57.0 
                 30.2 
                 56.5 
                 30.2 
                 14.7 
               
               
                   
                 p(t-test) 
                   
                 2.7E−5 
                   
                 2.9E−4 
                   
                 0.73 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 36.2 
               
               
                   
                 n (Samp) 
                 190 
                 21 
                 190 
                 21 
                 190 
                 11 
               
               
                   
                 n (Patient) 
                 190 
                 21 
                 190 
                 21 
                 190 
                 11 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 1.90 
                 27.8 
                 1.90 
                 27.8 
                 1.90 
                 6.02 
               
               
                   
                 Average 
                 13.1 
                 38.9 
                 13.1 
                 38.9 
                 13.1 
                 11.5 
               
               
                   
                 Stdev 
                 33.8 
                 63.2 
                 33.8 
                 63.2 
                 33.8 
                 13.5 
               
               
                   
                 p(t-test) 
                   
                 0.017 
                   
                 0.017 
                   
                 0.91 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.135 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 31.3 
               
               
                   
                 n (Samp) 
                 295 
                 11 
                 295 
                 11 
                 295 
                 6 
               
               
                   
                 n (Patient) 
                 295 
                 11 
                 295 
                 11 
                 295 
                 6 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 1.60 
                 35.3 
                 1.60 
                 29.0 
                 1.60 
                 3.34 
               
               
                   
                 Average 
                 9.22 
                 53.2 
                 9.22 
                 46.6 
                 9.22 
                 14.0 
               
               
                   
                 Stdev 
                 29.8 
                 64.3 
                 29.8 
                 64.7 
                 29.8 
                 15.7 
               
               
                   
                 p(t-test) 
                   
                 6.7E−6 
                   
                 1.2E−4 
                   
                 0.64 
               
               
                   
                 Min 
                 0.00804 
                 0.534 
                 0.00804 
                 0.534 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 36.2 
               
               
                   
                 n (Samp) 
                 134 
                 15 
                 134 
                 15 
                 134 
                 9 
               
               
                   
                 n (Patient) 
                 134 
                 15 
                 134 
                 15 
                 134 
                 9 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.79 
                 0.70 
                 0.81 
                 0.79 
                 0.70 
                 0.80 
                 0.68 
                 0.65 
                 0.67 
               
               
                 SE 
                 0.061 
                 0.089 
                 0.070 
                 0.061 
                 0.089 
                 0.070 
                 0.091 
                 0.12 
                 0.10 
               
               
                 p 
                 1.9E−6 
                 0.022 
                 1.0E−5 
                 2.7E−6 
                 0.023 
                 1.5E−5 
                 0.042 
                 0.23 
                 0.089 
               
               
                 nCohort 1 
                 190 
                 295 
                 134 
                 190 
                 295 
                 134 
                 190 
                 295 
                 134 
               
               
                 nCohort 2 
                 21 
                 11 
                 15 
                 21 
                 11 
                 15 
                 11 
                 6 
                 9 
               
               
                 Cutoff 1 
                 3.33 
                 1.95 
                 3.33 
                 3.33 
                 1.95 
                 3.33 
                 1.52 
                 0.570 
                 1.52 
               
               
                 Sens 1 
                 71% 
                 73% 
                 73% 
                 71% 
                 73% 
                 73% 
                 73% 
                 83% 
                 78% 
               
               
                 Spec 1 
                 65% 
                 51% 
                 60% 
                 65% 
                 51% 
                 60% 
                 54% 
                 41% 
                 49% 
               
               
                 Cutoff 2 
                 1.52 
                 0.570 
                 1.95 
                 1.52 
                 0.570 
                 1.95 
                 0.541 
                 0.570 
                 0.544 
               
               
                 Sens 2 
                 81% 
                 82% 
                 80% 
                 81% 
                 82% 
                 80% 
                 82% 
                 83% 
                 89% 
               
               
                 Spec 2 
                 54% 
                 41% 
                 56% 
                 54% 
                 41% 
                 56% 
                 48% 
                 41% 
                 45% 
               
               
                 Cutoff 3 
                 0.371 
                 0.134 
                 0.544 
                 0.371 
                 0.134 
                 0.544 
                 0.134 
                 0.134 
                 0.00804 
               
               
                 Sens 3 
                 90% 
                 91% 
                 93% 
                 90% 
                 91% 
                 93% 
                 91% 
                 100%  
                 100%  
               
               
                 Spec 3 
                 48% 
                 37% 
                 45% 
                 48% 
                 37% 
                 45% 
                 45% 
                 37% 
                  1% 
               
               
                 Cutoff 4 
                 4.12 
                 6.43 
                 4.69 
                 4.12 
                 6.43 
                 4.69 
                 4.12 
                 6.43 
                 4.69 
               
               
                 Sens 4 
                 67% 
                 64% 
                 67% 
                 67% 
                 55% 
                 67% 
                 45% 
                 50% 
                 44% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 6.66 
                 11.6 
                 8.08 
                 6.66 
                 11.6 
                 8.08 
                 6.66 
                 11.6 
                 8.08 
               
               
                 Sens 5 
                 62% 
                 55% 
                 67% 
                 62% 
                 55% 
                 67% 
                 45% 
                 33% 
                 44% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
               
               
                 Cutoff 6 
                 14.8 
                 28.5 
                 14.8 
                 14.8 
                 28.5 
                 14.8 
                 14.8 
                 28.5 
                 14.8 
               
               
                 Sens 6 
                 57% 
                 45% 
                 60% 
                 57% 
                 45% 
                 60% 
                 36% 
                 17% 
                 44% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 &gt;4.2 
                 2.0 
                 &gt;3.3 
                 &gt;4.2 
                 2.0 
                 &gt;3.3 
                 &gt;3.2 
                 &gt;2.1 
                 &gt;3.2 
               
               
                 p Value 
                 &lt;0.20 
                 0.57 
                 &lt;0.32 
                 &lt;0.20 
                 0.57 
                 &lt;0.32 
                 &lt;0.32 
                 &lt;0.56 
                 &lt;0.33 
               
               
                 95% CI of 
                 &gt;0.46 
                 0.18 
                 &gt;0.32 
                 &gt;0.46 
                 0.18 
                 &gt;0.32 
                 &gt;0.32 
                 &gt;0.18 
                 &gt;0.31 
               
               
                 OR Quart2 
                 na 
                 23 
                 na 
                 na 
                 23 
                 na 
                 na 
                 na 
                 na 
               
               
                 OR Quart 3 
                 &gt;4.2 
                 2.0 
                 &gt;2.1 
                 &gt;4.2 
                 2.0 
                 &gt;2.1 
                 &gt;3.2 
                 &gt;1.0 
                 &gt;2.1 
               
               
                 p Value 
                 &lt;0.20 
                 0.57 
                 &lt;0.55 
                 &lt;0.20 
                 0.57 
                 &lt;0.55 
                 &lt;0.32 
                 &lt;0.99 
                 &lt;0.56 
               
               
                 95% CI of 
                 &gt;0.46 
                 0.18 
                 &gt;0.18 
                 &gt;0.46 
                 0.18 
                 &gt;0.18 
                 &gt;0.32 
                 &gt;0.062 
                 &gt;0.18 
               
               
                 OR Quart3 
                 na 
                 23 
                 na 
                 na 
                 23 
                 na 
                 na 
                 na 
                 na 
               
               
                 OR Quart 4 
                 &gt;17 
                 6.3 
                 &gt;13 
                 &gt;17 
                 6.3 
                 &gt;13 
                 &gt;5.4 
                 &gt;3.1 
                 &gt;4.4 
               
               
                 p Value 
                 &lt;0.0076 
                 0.091 
                 &lt;0.017 
                 &lt;0.0076 
                 0.091 
                 &lt;0.017 
                 &lt;0.13 
                 &lt;0.33 
                 &lt;0.20 
               
               
                 95% CI of 
                 &gt;2.1 
                 0.74 
                 &gt;1.6 
                 &gt;2.1 
                 0.74 
                 &gt;1.6 
                 &gt;0.61 
                 &gt;0.31 
                 &gt;0.46 
               
               
                 OR Quart4 
                 na 
                 54 
                 na 
                 na 
                 54 
                 na 
                 na 
                 na 
                 na 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 382 
                 3580 
                 382 
                 3580 
                 382 
                 2150 
               
               
                   
                 Average 
                 828 
                 5520 
                 828 
                 4430 
                 828 
                 2820 
               
               
                   
                 Stdev 
                 1360 
                 6880 
                 1360 
                 5560 
                 1360 
                 1670 
               
               
                   
                 p(t-test) 
                   
                 2.4E−8 
                   
                 4.5E−7 
                   
                 3.6E−4 
               
               
                   
                 Min 
                 1.00E−9 
                 99.0 
                 1.00E−9 
                 99.0 
                 1.00E−9 
                 326 
               
               
                   
                 Max 
                 9810 
                 21100 
                 9810 
                 21100 
                 9810 
                 5370 
               
               
                   
                 n (Samp) 
                 98 
                 12 
                 98 
                 12 
                 98 
                 7 
               
               
                   
                 n (Patient) 
                 98 
                 12 
                 98 
                 12 
                 98 
                 7 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 494 
                 3030 
                 494 
                 3030 
                 nd 
                 nd 
               
               
                   
                 Average 
                 1230 
                 5100 
                 1230 
                 5100 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 2230 
                 6800 
                 2230 
                 6800 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 2.6E−4 
                   
                 2.6E−4 
                 nd 
                 nd 
               
               
                   
                 Min 
                 1.00E−9 
                 99.0 
                 1.00E−9 
                 99.0 
                 nd 
                 nd 
               
               
                   
                 Max 
                 21100 
                 18400 
                 21100 
                 18400 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 159 
                 6 
                 159 
                 6 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 159 
                 6 
                 159 
                 6 
                 nd 
                 nd 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 371 
                 4150 
                 371 
                 4150 
                 371 
                 2930 
               
               
                   
                 Average 
                 873 
                 7420 
                 873 
                 5790 
                 873 
                 2930 
               
               
                   
                 Stdev 
                 1480 
                 7810 
                 1480 
                 6420 
                 1480 
                 1810 
               
               
                   
                 p(t-test) 
                   
                 1.5E−9 
                   
                 1.1E−7 
                   
                 0.0016 
               
               
                   
                 Min 
                 1.00E−9 
                 326 
                 1.00E−9 
                 326 
                 1.00E−9 
                 326 
               
               
                   
                 Max 
                 9810 
                 21100 
                 9810 
                 21100 
                 9810 
                 5370 
               
               
                   
                 n (Samp) 
                 82 
                 8 
                 82 
                 8 
                 82 
                 6 
               
               
                   
                 n (Patient) 
                 82 
                 8 
                 82 
                 8 
                 82 
                 6 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.84 
                 0.75 
                 0.90 
                 0.84 
                 0.75 
                 0.90 
                 0.87 
                 nd 
                 0.85 
               
               
                 SE 
                 0.073 
                 0.12 
                 0.074 
                 0.074 
                 0.12 
                 0.075 
                 0.088 
                 nd 
                 0.10 
               
               
                 p 
                 3.6E−6 
                 0.030 
                 7.6E−8 
                 4.4E−6 
                 0.030 
                 1.4E−7 
                 2.9E−5 
                 nd 
                 5.0E−4 
               
               
                 nCohort 1 
                 98 
                 159 
                 82 
                 98 
                 159 
                 82 
                 98 
                 nd 
                 82 
               
               
                 nCohort 2 
                 12 
                 6 
                 8 
                 12 
                 6 
                 8 
                 7 
                 nd 
                 6 
               
               
                 Cutoff 1 
                 2070 
                 606 
                 3280 
                 2070 
                 606 
                 3280 
                 2070 
                 nd 
                 1840 
               
               
                 Sens 1 
                 75% 
                 83% 
                 75% 
                 75% 
                 83% 
                 75% 
                 71% 
                 nd 
                 83% 
               
               
                 Spec 1 
                 91% 
                 58% 
                 95% 
                 91% 
                 58% 
                 95% 
                 91% 
                 nd 
                 87% 
               
               
                 Cutoff 2 
                 606 
                 606 
                 2070 
                 606 
                 606 
                 2070 
                 1990 
                 nd 
                 1840 
               
               
                 Sens 2 
                 83% 
                 83% 
                 88% 
                 83% 
                 83% 
                 88% 
                 86% 
                 nd 
                 83% 
               
               
                 Spec 2 
                 68% 
                 58% 
                 89% 
                 68% 
                 58% 
                 89% 
                 89% 
                 nd 
                 87% 
               
               
                 Cutoff 3 
                 310 
                 88.6 
                 310 
                 310 
                 88.6 
                 310 
                 310 
                 nd 
                 310 
               
               
                 Sens 3 
                 92% 
                 100%  
                 100%  
                 92% 
                 100%  
                 100%  
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                 45% 
                 18% 
                 46% 
                 45% 
                 18% 
                 46% 
                 45% 
                 nd 
                 46% 
               
               
                 Cutoff 4 
                 730 
                 1150 
                 695 
                 730 
                 1150 
                 695 
                 730 
                 nd 
                 695 
               
               
                 Sens 4 
                 75% 
                 67% 
                 88% 
                 75% 
                 67% 
                 88% 
                 86% 
                 nd 
                 83% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 71% 
                 70% 
                 70% 
                 71% 
                 70% 
                 nd 
                 71% 
               
               
                 Cutoff 5 
                 1280 
                 1840 
                 1280 
                 1280 
                 1840 
                 1280 
                 1280 
                 nd 
                 1280 
               
               
                 Sens 5 
                 75% 
                 67% 
                 88% 
                 75% 
                 67% 
                 88% 
                 86% 
                 nd 
                 83% 
               
               
                 Spec 5 
                 81% 
                 81% 
                 80% 
                 81% 
                 81% 
                 80% 
                 81% 
                 nd 
                 80% 
               
               
                 Cutoff 6 
                 2070 
                 3280 
                 2140 
                 2070 
                 3280 
                 2140 
                 2070 
                 nd 
                 2140 
               
               
                 Sens 6 
                 75% 
                 50% 
                 75% 
                 75% 
                 50% 
                 75% 
                 71% 
                 nd 
                 50% 
               
               
                 Spec 6 
                 91% 
                 91% 
                 90% 
                 91% 
                 91% 
                 90% 
                 91% 
                 nd 
                 90% 
               
               
                 OR Quart 2 
                 0.96 
                 0 
                 &gt;1.0 
                 0.96 
                 0 
                 &gt;1.0 
                 &gt;1.0 
                 nd 
                 &gt;1.0 
               
               
                 p Value 
                 0.98 
                 na 
                 &lt;1.0 
                 0.98 
                 na 
                 &lt;1.0 
                 &lt;0.98 
                 nd 
                 &lt;0.97 
               
               
                 95% CI of 
                 0.057 
                 na 
                 &gt;0.059 
                 0.057 
                 na 
                 &gt;0.059 
                 &gt;0.062 
                 nd 
                 &gt;0.061 
               
               
                 OR Quart2 
                 16 
                 na 
                 na 
                 16 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                 OR Quart 3 
                 1.0 
                 1.0 
                 &gt;0 
                 1.0 
                 1.0 
                 &gt;0 
                 &gt;0 
                 nd 
                 &gt;0 
               
               
                 p Value 
                 1.0 
                 1.0 
                 &lt;na   
                 1.0 
                 1.0 
                 &lt;na   
                 &lt;na   
                 nd 
                 &lt;na   
               
               
                 95% CI of 
                 0.059 
                 0.060 
                 &gt;na   
                 0.059 
                 0.060 
                 &gt;na   
                 &gt;na   
                 nd 
                 &gt;na   
               
               
                 OR Quart3 
                 17 
                 17 
                 na 
                 17 
                 17 
                 na 
                 na 
                 nd 
                 na 
               
               
                 OR Quart 4 
                 12 
                 4.2 
                 &gt;9.6 
                 12 
                 4.2 
                 &gt;9.6 
                 &gt;7.4 
                 nd 
                 &gt;6.5 
               
               
                 p Value 
                 0.022 
                 0.21 
                 &lt;0.043 
                 0.022 
                 0.21 
                 &lt;0.043 
                 &lt;0.073 
                 nd 
                 &lt;0.10 
               
               
                 95% CI of 
                 1.4 
                 0.45 
                 &gt;1.1 
                 1.4 
                 0.45 
                 &gt;1.1 
                 &gt;0.83 
                 nd 
                 &gt;0.69 
               
               
                 OR Quart4 
                 110 
                 39 
                 na 
                 110 
                 39 
                 na 
                 na 
                 nd 
                 na 
               
               
                   
               
            
           
           
               
            
               
                 Cathepsin B 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.556 
                 4.74 
                 0.556 
                 4.74 
                 0.556 
                 2.27 
               
               
                   
                 Average 
                 2.13 
                 12.7 
                 2.13 
                 12.7 
                 2.13 
                 2.62 
               
               
                   
                 Stdev 
                 7.41 
                 19.1 
                 7.41 
                 19.1 
                 7.41 
                 2.21 
               
               
                   
                 p(t-test) 
                   
                 2.7E−4 
                   
                 2.7E−4 
                   
                 0.86 
               
               
                   
                 Min 
                 1.00E−9 
                 0.310 
                 1.00E−9 
                 0.310 
                 1.00E−9 
                 0.310 
               
               
                   
                 Max 
                 72.4 
                 64.9 
                 72.4 
                 64.9 
                 72.4 
                 6.19 
               
               
                   
                 n (Samp) 
                 102 
                 12 
                 102 
                 12 
                 102 
                 7 
               
               
                   
                 n (Patient) 
                 102 
                 12 
                 102 
                 12 
                 102 
                 7 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.897 
                 9.47 
                 0.897 
                 9.47 
                 nd 
                 nd 
               
               
                   
                 Average 
                 3.16 
                 12.6 
                 3.16 
                 12.6 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 9.92 
                 12.0 
                 9.92 
                 12.0 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.025 
                   
                 0.025 
                 nd 
                 nd 
               
               
                   
                 Min 
                 1.00E−9 
                 0.405 
                 1.00E−9 
                 0.405 
                 nd 
                 nd 
               
               
                   
                 Max 
                 78.1 
                 29.7 
                 78.1 
                 29.7 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 162 
                 6 
                 162 
                 6 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 162 
                 6 
                 162 
                 6 
                 nd 
                 nd 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.677 
                 4.74 
                 0.677 
                 4.74 
                 0.677 
                 2.13 
               
               
                   
                 Average 
                 2.26 
                 14.2 
                 2.26 
                 14.2 
                 2.26 
                 2.68 
               
               
                   
                 Stdev 
                 7.97 
                 22.7 
                 7.97 
                 22.7 
                 7.97 
                 2.42 
               
               
                   
                 p(t-test) 
                   
                 0.0015 
                   
                 0.0015 
                   
                 0.90 
               
               
                   
                 Min 
                 1.00E−9 
                 0.310 
                 1.00E−9 
                 0.310 
                 1.00E−9 
                 0.310 
               
               
                   
                 Max 
                 72.4 
                 64.9 
                 72.4 
                 64.9 
                 72.4 
                 6.19 
               
               
                   
                 n (Samp) 
                 87 
                 8 
                 87 
                 8 
                 87 
                 6 
               
               
                   
                 n (Patient) 
                 87 
                 8 
                 87 
                 8 
                 87 
                 6 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.79 
                 0.82 
                 0.77 
                 0.79 
                 0.82 
                 0.77 
                 0.71 
                 nd 
                 0.69 
               
               
                 SE 
                 0.081 
                 0.11 
                 0.10 
                 0.081 
                 0.11 
                 0.10 
                 0.11 
                 nd 
                 0.12 
               
               
                 p 
                 4.2E−4 
                 0.0030 
                 0.0064 
                 4.2E−4 
                 0.0030 
                 0.0064 
                 0.059 
                 nd 
                 0.13 
               
               
                 nCohort 1 
                 102 
                 162 
                 87 
                 102 
                 162 
                 87 
                 102 
                 nd 
                 87 
               
               
                 nCohort 2 
                 12 
                 6 
                 8 
                 12 
                 6 
                 8 
                 7 
                 nd 
                 6 
               
               
                 Cutoff 1 
                 0.949 
                 2.16 
                 0.949 
                 0.949 
                 2.16 
                 0.949 
                 0.888 
                 nd 
                 0.604 
               
               
                 Sens 1 
                 75% 
                 83% 
                 75% 
                 75% 
                 83% 
                 75% 
                 71% 
                 nd 
                 83% 
               
               
                 Spec 1 
                 58% 
                 77% 
                 56% 
                 58% 
                 77% 
                 56% 
                 58% 
                 nd 
                 49% 
               
               
                 Cutoff 2 
                 0.888 
                 2.16 
                 0.888 
                 0.888 
                 2.16 
                 0.888 
                 0.604 
                 nd 
                 0.604 
               
               
                 Sens 2 
                 83% 
                 83% 
                 88% 
                 83% 
                 83% 
                 88% 
                 86% 
                 nd 
                 83% 
               
               
                 Spec 2 
                 58% 
                 77% 
                 56% 
                 58% 
                 77% 
                 56% 
                 53% 
                 nd 
                 49% 
               
               
                 Cutoff 3 
                 0.397 
                 0.397 
                 0.309 
                 0.397 
                 0.397 
                 0.309 
                 0.309 
                 nd 
                 0.309 
               
               
                 Sens 3 
                 92% 
                 100%  
                 100%  
                 92% 
                 100%  
                 100%  
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                 40% 
                 31% 
                 31% 
                 40% 
                 31% 
                 31% 
                 32% 
                 nd 
                 31% 
               
               
                 Cutoff 4 
                 1.42 
                 1.67 
                 1.49 
                 1.42 
                 1.67 
                 1.49 
                 1.42 
                 nd 
                 1.49 
               
               
                 Sens 4 
                 67% 
                 83% 
                 62% 
                 67% 
                 83% 
                 62% 
                 57% 
                 nd 
                 50% 
               
               
                 Spec 4 
                 71% 
                 70% 
                 70% 
                 71% 
                 70% 
                 70% 
                 71% 
                 nd 
                 70% 
               
               
                 Cutoff 5 
                 2.04 
                 2.74 
                 2.04 
                 2.04 
                 2.74 
                 2.04 
                 2.04 
                 nd 
                 2.04 
               
               
                 Sens 5 
                 67% 
                 67% 
                 62% 
                 67% 
                 67% 
                 62% 
                 57% 
                 nd 
                 50% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 nd 
                 80% 
               
               
                 Cutoff 6 
                 3.88 
                 5.61 
                 3.76 
                 3.88 
                 5.61 
                 3.76 
                 3.88 
                 nd 
                 3.76 
               
               
                 Sens 6 
                 50% 
                 67% 
                 50% 
                 50% 
                 67% 
                 50% 
                 29% 
                 nd 
                 33% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 91% 
                 90% 
                 90% 
                 91% 
                 90% 
                 nd 
                 91% 
               
               
                 OR Quart 2 
                 &gt;2.1 
                 &gt;1.0 
                 &gt;1.0 
                 &gt;2.1 
                 &gt;1.0 
                 &gt;1.0 
                 &gt;1.0 
                 nd 
                 &gt;2.2 
               
               
                 p Value 
                 &lt;0.56 
                 &lt;0.99 
                 &lt;1.0 
                 &lt;0.56 
                 &lt;0.99 
                 &lt;1.0 
                 &lt;0.98 
                 nd 
                 &lt;0.53 
               
               
                 95% CI of 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.059 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.059 
                 &gt;0.062 
                 nd 
                 &gt;0.18 
               
               
                 OR Quart2 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                 OR Quart 3 
                 &gt;2.2 
                 &gt;1.0 
                 &gt;2.1 
                 &gt;2.2 
                 &gt;1.0 
                 &gt;2.1 
                 &gt;2.2 
                 nd 
                 &gt;1.0 
               
               
                 p Value 
                 &lt;0.54 
                 &lt;0.99 
                 &lt;0.56 
                 &lt;0.54 
                 &lt;0.99 
                 &lt;0.56 
                 &lt;0.54 
                 nd 
                 &lt;0.98 
               
               
                 95% CI of 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.18 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.18 
                 &gt;0.18 
                 nd 
                 &gt;0.062 
               
               
                 OR Quart3 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                 OR Quart 4 
                 &gt;11 
                 &gt;4.4 
                 &gt;6.1 
                 &gt;11 
                 &gt;4.4 
                 &gt;6.1 
                 &gt;4.5 
                 nd 
                 &gt;3.3 
               
               
                 p Value 
                 &lt;0.031 
                 &lt;0.19 
                 &lt;0.11 
                 &lt;0.031 
                 &lt;0.19 
                 &lt;0.11 
                 &lt;0.19 
                 nd 
                 &lt;0.32 
               
               
                 95% CI of 
                 &gt;1.2 
                 &gt;0.47 
                 &gt;0.65 
                 &gt;1.2 
                 &gt;0.47 
                 &gt;0.65 
                 &gt;0.47 
                 nd 
                 &gt;0.32 
               
               
                 OR Quart4 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                   
               
            
           
           
               
            
               
                 Dipeptidyl peptidase IV 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 143 
                 2270 
                 143 
                 2270 
                 143 
                 2270 
               
               
                 Average 
                 9210 
                 2860 
                 9210 
                 2860 
                 9210 
                 2490 
               
               
                 Stdev 
                 74700 
                 2490 
                 74700 
                 2490 
                 74700 
                 2330 
               
               
                 p(t-test) 
                   
                 0.79 
                   
                 0.79 
                   
                 0.83 
               
               
                 Min 
                 0.200 
                 0.651 
                 0.200 
                 0.651 
                 0.200 
                 10.1 
               
               
                 Max 
                 677000 
                 7150 
                 677000 
                 7150 
                 677000 
                 5420 
               
               
                 n (Samp) 
                 82 
                 10 
                 82 
                 10 
                 82 
                 6 
               
               
                 n (Patient) 
                 82 
                 10 
                 82 
                 10 
                 82 
                 6 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 103 
                 2270 
                 103 
                 2270 
                 nd 
                 nd 
               
               
                 Average 
                 604 
                 2720 
                 604 
                 2720 
                 nd 
                 nd 
               
               
                 Stdev 
                 1400 
                 2100 
                 1400 
                 2100 
                 nd 
                 nd 
               
               
                 p(t-test) 
                   
                 1.0E−3 
                   
                 1.0E−3 
                 nd 
                 nd 
               
               
                 Min 
                 0.200 
                 10.1 
                 0.200 
                 10.1 
                 nd 
                 nd 
               
               
                 Max 
                 9980 
                 5420 
                 9980 
                 5420 
                 nd 
                 nd 
               
               
                 n (Samp) 
                 71 
                 6 
                 71 
                 6 
                 nd 
                 nd 
               
               
                 n (Patient) 
                 71 
                 6 
                 71 
                 6 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 nd 
                 0.81 
                 0.74 
                 nd 
                 0.81 
                 0.68 
                 nd 
                 nd 
               
               
                 SE 
                 0.094 
                 nd 
                 0.11 
                 0.094 
                 nd 
                 0.11 
                 0.12 
                 nd 
                 nd 
               
               
                 p 
                 0.012 
                 nd 
                 0.0037 
                 0.012 
                 nd 
                 0.0037 
                 0.15 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 82 
                 nd 
                 71 
                 82 
                 nd 
                 71 
                 82 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 10 
                 nd 
                 6 
                 10 
                 nd 
                 6 
                 6 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 1210 
                 nd 
                 1190 
                 1210 
                 nd 
                 1190 
                 12.4 
                 nd 
                 nd 
               
               
                 Sens 1 
                 70% 
                 nd 
                 83% 
                 70% 
                 nd 
                 83% 
                 83% 
                 nd 
                 nd 
               
               
                 Spec 1 
                 82% 
                 nd 
                 86% 
                 82% 
                 nd 
                 86% 
                 18% 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 659 
                 nd 
                 1190 
                 659 
                 nd 
                 1190 
                 12.4 
                 nd 
                 nd 
               
               
                 Sens 2 
                 80% 
                 nd 
                 83% 
                 80% 
                 nd 
                 83% 
                 83% 
                 nd 
                 nd 
               
               
                 Spec 2 
                 73% 
                 nd 
                 86% 
                 73% 
                 nd 
                 86% 
                 18% 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 9.55 
                 nd 
                 9.55 
                 9.55 
                 nd 
                 9.55 
                 9.55 
                 nd 
                 nd 
               
               
                 Sens 3 
                 90% 
                 nd 
                 100%  
                 90% 
                 nd 
                 100%  
                 100%  
                 nd 
                 nd 
               
               
                 Spec 3 
                 15% 
                 nd 
                 17% 
                 15% 
                 nd 
                 17% 
                 15% 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 545 
                 nd 
                 407 
                 545 
                 nd 
                 407 
                 545 
                 nd 
                 nd 
               
               
                 Sens 4 
                 80% 
                 nd 
                 83% 
                 80% 
                 nd 
                 83% 
                 67% 
                 nd 
                 nd 
               
               
                 Spec 4 
                 71% 
                 nd 
                 70% 
                 71% 
                 nd 
                 70% 
                 71% 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 1190 
                 nd 
                 942 
                 1190 
                 nd 
                 942 
                 1190 
                 nd 
                 nd 
               
               
                 Sens 5 
                 70% 
                 nd 
                 83% 
                 70% 
                 nd 
                 83% 
                 67% 
                 nd 
                 nd 
               
               
                 Spec 5 
                 80% 
                 nd 
                 80% 
                 80% 
                 nd 
                 80% 
                 80% 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 2020 
                 nd 
                 1810 
                 2020 
                 nd 
                 1810 
                 2020 
                 nd 
                 nd 
               
               
                 Sens 6 
                 50% 
                 nd 
                 67% 
                 50% 
                 nd 
                 67% 
                 50% 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 0 
                 nd 
                 0 
                 0 
                 nd 
                 0 
                 0 
                 nd 
                 nd 
               
               
                 p Value 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 nd 
               
               
                 95% CI of 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 0.48 
                 nd 
                 0 
                 0.48 
                 nd 
                 0 
                 0 
                 nd 
                 nd 
               
               
                 p Value 
                 0.56 
                 nd 
                 na 
                 0.56 
                 nd 
                 na 
                 na 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.040 
                 nd 
                 na 
                 0.040 
                 nd 
                 na 
                 na 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 5.7 
                 nd 
                 na 
                 5.7 
                 nd 
                 na 
                 na 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 4.6 
                 nd 
                 6.0 
                 4.6 
                 nd 
                 6.0 
                 2.2 
                 nd 
                 nd 
               
               
                 p Value 
                 0.079 
                 nd 
                 0.12 
                 0.079 
                 nd 
                 0.12 
                 0.39 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.84 
                 nd 
                 0.63 
                 0.84 
                 nd 
                 0.63 
                 0.36 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 25 
                 nd 
                 57 
                 25 
                 nd 
                 57 
                 14 
                 nd 
                 nd 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 Comparison of marker levels in EDTA samples collected from Cohort 1 (patients that 
               
               
                 did not progress beyond RIFLE stage 0) and in EDTA samples collected from subjects 
               
               
                 at 0, 24 hours, and 48 hours prior to reaching stage R, I or F in Cohort 2. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 2.38 
                 2.60 
                 2.38 
                 2.37 
                 2.38 
                 2.46 
               
               
                 Average 
                 2.90 
                 3.66 
                 2.90 
                 3.86 
                 2.90 
                 3.17 
               
               
                 Stdev 
                 1.90 
                 3.11 
                 1.90 
                 3.82 
                 1.90 
                 2.08 
               
               
                 p(t-test) 
                   
                 0.020 
                   
                 0.0058 
                   
                 0.49 
               
               
                 Min 
                 0.850 
                 0.759 
                 0.850 
                 1.14 
                 0.850 
                 1.04 
               
               
                 Max 
                 12.1 
                 16.2 
                 12.1 
                 22.7 
                 12.1 
                 9.51 
               
               
                 n (Samp) 
                 263 
                 51 
                 263 
                 56 
                 263 
                 26 
               
               
                 n (Patient) 
                 111 
                 51 
                 111 
                 56 
                 111 
                 26 
               
            
           
           
               
            
               
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 2.38 
                 4.85 
                 2.38 
                 4.23 
                 2.38 
                 4.37 
               
               
                 Average 
                 2.98 
                 5.96 
                 2.98 
                 5.76 
                 2.98 
                 4.24 
               
               
                 Stdev 
                 2.03 
                 4.33 
                 2.03 
                 5.04 
                 2.03 
                 2.01 
               
               
                 p(t-test) 
                   
                 1.4E−8 
                   
                 3.7E−8 
                   
                 0.027 
               
               
                 Min 
                 0.729 
                 0.759 
                 0.729 
                 1.51 
                 0.729 
                 1.54 
               
               
                 Max 
                 16.7 
                 16.2 
                 16.7 
                 22.7 
                 16.7 
                 7.60 
               
               
                 n (Samp) 
                 466 
                 18 
                 466 
                 21 
                 466 
                 13 
               
               
                 n (Patient) 
                 180 
                 18 
                 180 
                 21 
                 180 
                 13 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Median 
                 2.46 
                 3.00 
                 2.46 
                 2.54 
                 2.46 
                 2.45 
               
               
                 Average 
                 2.96 
                 3.80 
                 2.96 
                 3.78 
                 2.96 
                 3.41 
               
               
                 Stdev 
                 1.87 
                 2.87 
                 1.87 
                 3.19 
                 1.87 
                 3.29 
               
               
                 p(t-test) 
                   
                 0.011 
                   
                 0.016 
                   
                 0.32 
               
               
                 Min 
                 0.899 
                 1.00 
                 0.899 
                 1.14 
                 0.899 
                 1.04 
               
               
                 Max 
                 12.1 
                 14.6 
                 12.1 
                 16.5 
                 12.1 
                 16.2 
               
               
                 n (Samp) 
                 221 
                 50 
                 221 
                 52 
                 221 
                 23 
               
               
                 n (Patient) 
                 91 
                 50 
                 91 
                 52 
                 91 
                 23 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.57 
                 0.74 
                 0.59 
                 0.55 
                 0.72 
                 0.55 
                 0.55 
                 0.71 
                 0.52 
               
               
                 SE 
                 0.045 
                 0.068 
                 0.046 
                 0.043 
                 0.064 
                 0.045 
                 0.061 
                 0.082 
                 0.064 
               
               
                 p 
                 0.14 
                 4.4E−4 
                 0.051 
                 0.24 
                 7.0E−4 
                 0.22 
                 0.45 
                 0.0093 
                 0.81 
               
               
                 nCohort 1 
                 263 
                 466 
                 221 
                 263 
                 466 
                 221 
                 263 
                 466 
                 221 
               
               
                 nCohort 2 
                 51 
                 18 
                 50 
                 56 
                 21 
                 52 
                 26 
                 13 
                 23 
               
               
                 Cutoff 1 
                 1.93 
                 2.86 
                 2.08 
                 1.80 
                 2.73 
                 1.88 
                 2.10 
                 2.45 
                 1.66 
               
               
                 Sens 1 
                 71% 
                 72% 
                 70% 
                 71% 
                 71% 
                 71% 
                 73% 
                 77% 
                 74% 
               
               
                 Spec 1 
                 37% 
                 62% 
                 38% 
                 32% 
                 60% 
                 33% 
                 41% 
                 52% 
                 27% 
               
               
                 Cutoff 2 
                 1.70 
                 2.13 
                 1.74 
                 1.62 
                 1.88 
                 1.62 
                 1.59 
                 2.19 
                 1.54 
               
               
                 Sens 2 
                 82% 
                 83% 
                 80% 
                 80% 
                 81% 
                 81% 
                 81% 
                 85% 
                 83% 
               
               
                 Spec 2 
                 29% 
                 42% 
                 29% 
                 26% 
                 33% 
                 26% 
                 25% 
                 44% 
                 23% 
               
               
                 Cutoff 3 
                 1.40 
                 1.70 
                 1.59 
                 1.46 
                 1.76 
                 1.43 
                 1.37 
                 1.88 
                 1.37 
               
               
                 Sens 3 
                 90% 
                 94% 
                 90% 
                 91% 
                 90% 
                 90% 
                 92% 
                 92% 
                 91% 
               
               
                 Spec 3 
                 19% 
                 27% 
                 25% 
                 20% 
                 30% 
                 19% 
                 18% 
                 33% 
                 19% 
               
               
                 Cutoff 4 
                 3.23 
                 3.27 
                 3.43 
                 3.23 
                 3.27 
                 3.43 
                 3.23 
                 3.27 
                 3.43 
               
               
                 Sens 4 
                 37% 
                 67% 
                 40% 
                 32% 
                 67% 
                 35% 
                 35% 
                 62% 
                 35% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 71% 
                 70% 
                 70% 
                 71% 
                 70% 
                 70% 
                 71% 
               
               
                 Cutoff 5 
                 3.85 
                 4.11 
                 4.15 
                 3.85 
                 4.11 
                 4.15 
                 3.85 
                 4.11 
                 4.15 
               
               
                 Sens 5 
                 29% 
                 61% 
                 28% 
                 29% 
                 57% 
                 27% 
                 23% 
                 62% 
                 13% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 5.37 
                 5.50 
                 5.50 
                 5.37 
                 5.50 
                 5.50 
                 5.37 
                 5.50 
                 5.50 
               
               
                 Sens 6 
                 18% 
                 44% 
                 16% 
                 18% 
                 29% 
                 19% 
                 12% 
                 23% 
                  9% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 2.4 
                 3.1 
                 1.8 
                 1.7 
                 1.5 
                 1.3 
                 1.2 
                 2.0 
                 1.5 
               
               
                 p Value 
                 0.077 
                 0.34 
                 0.23 
                 0.23 
                 0.66 
                 0.51 
                 0.75 
                 0.57 
                 0.54 
               
               
                 95% CI of 
                 0.91 
                 0.31 
                 0.68 
                 0.73 
                 0.25 
                 0.56 
                 0.35 
                 0.18 
                 0.43 
               
               
                 OR Quart2 
                 6.2 
                 30 
                 5.0 
                 3.8 
                 9.1 
                 3.2 
                 4.2 
                 22 
                 4.9 
               
               
                 OR Quart 3 
                 2.0 
                 2.0 
                 2.4 
                 0.99 
                 0.99 
                 0.89 
                 1.2 
                 2.0 
                 1.0 
               
               
                 p Value 
                 0.16 
                 0.57 
                 0.073 
                 0.97 
                 0.99 
                 0.81 
                 0.75 
                 0.57 
                 1.0 
               
               
                 95% CI of 
                 0.76 
                 0.18 
                 0.92 
                 0.40 
                 0.14 
                 0.35 
                 0.35 
                 0.18 
                 0.27 
               
               
                 OR Quart3 
                 5.4 
                 23 
                 6.4 
                 2.4 
                 7.2 
                 2.3 
                 4.2 
                 22 
                 3.6 
               
               
                 OR Quart 4 
                 2.6 
                 13 
                 2.6 
                 1.7 
                 7.7 
                 1.7 
                 1.9 
                 8.4 
                 1.2 
               
               
                 p Value 
                 0.051 
                 0.014 
                 0.048 
                 0.23 
                 0.0078 
                 0.22 
                 0.28 
                 0.046 
                 0.75 
               
               
                 95% CI of 
                 1.00 
                 1.7 
                 1.0 
                 0.73 
                 1.7 
                 0.73 
                 0.60 
                 1.0 
                 0.35 
               
               
                 OR Quart4 
                 6.7 
                 100 
                 6.9 
                 3.8 
                 35 
                 3.9 
                 5.9 
                 68 
                 4.2 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 3630 
                 3850 
                 3630 
                 3360 
                 3630 
                 4440 
               
               
                   
                 Average 
                 3940 
                 4030 
                 3940 
                 4520 
                 3940 
                 4580 
               
               
                   
                 Stdev 
                 1330 
                 1360 
                 1330 
                 4260 
                 1330 
                 2250 
               
               
                   
                 p(t-test) 
                   
                 0.81 
                   
                 0.37 
                   
                 0.26 
               
               
                   
                 Min 
                 1700 
                 1120 
                 1700 
                 2100 
                 1700 
                 1870 
               
               
                   
                 Max 
                 7950 
                 6070 
                 7950 
                 23300 
                 7950 
                 8860 
               
               
                   
                 n (Samp) 
                 55 
                 16 
                 55 
                 24 
                 55 
                 8 
               
               
                   
                 n (Patient) 
                 54 
                 16 
                 54 
                 24 
                 54 
                 8 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 4180 
                 3800 
                 4180 
                 3360 
                 4180 
                 4410 
               
               
                   
                 Average 
                 4290 
                 4040 
                 4290 
                 4510 
                 4290 
                 3960 
               
               
                   
                 Stdev 
                 1610 
                 1490 
                 1610 
                 4260 
                 1610 
                 1550 
               
               
                   
                 p(t-test) 
                   
                 0.61 
                   
                 0.75 
                   
                 0.62 
               
               
                   
                 Min 
                 1700 
                 1120 
                 1700 
                 2100 
                 1700 
                 1870 
               
               
                   
                 Max 
                 9230 
                 6070 
                 9230 
                 23300 
                 9230 
                 6200 
               
               
                   
                 n (Samp) 
                 49 
                 14 
                 49 
                 24 
                 49 
                 7 
               
               
                   
                 n (Patient) 
                 45 
                 14 
                 45 
                 24 
                 45 
                 7 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.55 
                 nd 
                 0.48 
                 0.46 
                 nd 
                 0.41 
                 0.60 
                 nd 
                 0.49 
               
               
                 SE 
                 0.084 
                 nd 
                 0.089 
                 0.072 
                 nd 
                 0.073 
                 0.11 
                 nd 
                 0.12 
               
               
                 p 
                 0.57 
                 nd 
                 0.79 
                 0.54 
                 nd 
                 0.24 
                 0.36 
                 nd 
                 0.91 
               
               
                 nCohort 1 
                 55 
                 nd 
                 49 
                 55 
                 nd 
                 49 
                 55 
                 nd 
                 49 
               
               
                 nCohort 2 
                 16 
                 nd 
                 14 
                 24 
                 nd 
                 24 
                 8 
                 nd 
                 7 
               
               
                 Cutoff 1 
                 3490 
                 nd 
                 3310 
                 2630 
                 nd 
                 2630 
                 3630 
                 nd 
                 3630 
               
               
                 Sens 1 
                 75% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 75% 
                 nd 
                 71% 
               
               
                 Spec 1 
                 45% 
                 nd 
                 33% 
                 11% 
                 nd 
                 12% 
                 51% 
                 nd 
                 37% 
               
               
                 Cutoff 2 
                 2770 
                 nd 
                 2510 
                 2110 
                 nd 
                 2110 
                 1900 
                 nd 
                 1900 
               
               
                 Sens 2 
                 81% 
                 nd 
                 86% 
                 83% 
                 nd 
                 83% 
                 88% 
                 nd 
                 86% 
               
               
                 Spec 2 
                 13% 
                 nd 
                 12% 
                 5% 
                 nd 
                  6% 
                  5% 
                 nd 
                  6% 
               
               
                 Cutoff 3 
                 2240 
                 nd 
                 2240 
                 2100 
                 nd 
                 2100 
                 1840 
                 nd 
                 1840 
               
               
                 Sens 3 
                 94% 
                 nd 
                 93% 
                 92% 
                 nd 
                 92% 
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                  9% 
                 nd 
                 10% 
                  5% 
                 nd 
                  6% 
                  4% 
                 nd 
                  4% 
               
               
                 Cutoff 4 
                 4320 
                 nd 
                 4690 
                 4320 
                 nd 
                 4690 
                 4320 
                 nd 
                 4690 
               
               
                 Sens 4 
                 44% 
                 nd 
                 36% 
                 38% 
                 nd 
                 29% 
                 62% 
                 nd 
                 29% 
               
               
                 Spec 4 
                 71% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
               
               
                 Cutoff 5 
                 4690 
                 nd 
                 5460 
                 4690 
                 nd 
                 5460 
                 4690 
                 nd 
                 5460 
               
               
                 Sens 5 
                 38% 
                 nd 
                 29% 
                 29% 
                 nd 
                 21% 
                 38% 
                 nd 
                 14% 
               
               
                 Spec 5 
                 80% 
                 nd 
                 82% 
                 80% 
                 nd 
                 82% 
                 80% 
                 nd 
                 82% 
               
               
                 Cutoff 6 
                 5580 
                 nd 
                 6490 
                 5580 
                 nd 
                 6490 
                 5580 
                 nd 
                 6490 
               
               
                 Sens 6 
                 12% 
                 nd 
                  0% 
                 17% 
                 nd 
                  4% 
                 25% 
                 nd 
                  0% 
               
               
                 Spec 6 
                 91% 
                 nd 
                 92% 
                 91% 
                 nd 
                 92% 
                 91% 
                 nd 
                 92% 
               
               
                 OR Quart 2 
                 0.65 
                 nd 
                 0.43 
                 0.17 
                 nd 
                 0.43 
                 0.43 
                 nd 
                 1.0 
               
               
                 p Value 
                 0.61 
                 nd 
                 0.37 
                 0.040 
                 nd 
                 0.30 
                 0.51 
                 nd 
                 1.0 
               
               
                 95% CI of 
                 0.12 
                 nd 
                 0.066 
                 0.030 
                 nd 
                 0.090 
                 0.035 
                 nd 
                 0.12 
               
               
                 OR Quart2 
                 3.5 
                 nd 
                 2.8 
                 0.92 
                 nd 
                 2.1 
                 5.3 
                 nd 
                 8.3 
               
               
                 OR Quart 3 
                 0.65 
                 nd 
                 1.0 
                 0.64 
                 nd 
                 0.83 
                 0.93 
                 nd 
                 0.46 
               
               
                 p Value 
                 0.61 
                 nd 
                 1.0 
                 0.51 
                 nd 
                 0.80 
                 0.94 
                 nd 
                 0.55 
               
               
                 95% CI of 
                 0.12 
                 nd 
                 0.20 
                 0.17 
                 nd 
                 0.20 
                 0.11 
                 nd 
                 0.037 
               
               
                 OR Quart3 
                 3.5 
                 nd 
                 5.0 
                 2.4 
                 nd 
                 3.4 
                 7.6 
                 nd 
                 5.8 
               
               
                 OR Quart 4 
                 1.6 
                 nd 
                 1.1 
                 1.1 
                 nd 
                 2.7 
                 1.5 
                 nd 
                 1.0 
               
               
                 p Value 
                 0.52 
                 nd 
                 0.92 
                 0.89 
                 nd 
                 0.15 
                 0.68 
                 nd 
                 1.0 
               
               
                 95% CI of 
                 0.37 
                 nd 
                 0.22 
                 0.30 
                 nd 
                 0.71 
                 0.21 
                 nd 
                 0.12 
               
               
                 OR Quart4 
                 7.2 
                 nd 
                 5.5 
                 3.9 
                 nd 
                 10 
                 11 
                 nd 
                 8.3 
               
               
                   
               
            
           
           
               
            
               
                 Neprilysin 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.689 
                 0.927 
                 0.689 
                 0.827 
                 0.689 
                 0.605 
               
               
                   
                 Average 
                 1.18 
                 1.27 
                 1.18 
                 1.20 
                 1.18 
                 0.816 
               
               
                   
                 Stdev 
                 1.12 
                 0.993 
                 1.12 
                 1.10 
                 1.12 
                 0.785 
               
               
                   
                 p(t-test) 
                   
                 0.76 
                   
                 0.93 
                   
                 0.38 
               
               
                   
                 Min 
                 0.0870 
                 0.183 
                 0.0870 
                 0.191 
                 0.0870 
                 0.244 
               
               
                   
                 Max 
                 4.92 
                 3.50 
                 4.92 
                 4.43 
                 4.92 
                 2.73 
               
               
                   
                 n (Samp) 
                 53 
                 16 
                 53 
                 24 
                 53 
                 8 
               
               
                   
                 n (Patient) 
                 52 
                 16 
                 52 
                 24 
                 52 
                 8 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.830 
                 0.839 
                 0.830 
                 0.771 
                 0.830 
                 0.604 
               
               
                   
                 Average 
                 1.35 
                 1.12 
                 1.35 
                 1.11 
                 1.35 
                 0.542 
               
               
                   
                 Stdev 
                 1.17 
                 0.997 
                 1.17 
                 1.06 
                 1.17 
                 0.148 
               
               
                   
                 p(t-test) 
                   
                 0.51 
                   
                 0.40 
                   
                 0.076 
               
               
                   
                 Min 
                 0.0870 
                 0.183 
                 0.0870 
                 0.191 
                 0.0870 
                 0.244 
               
               
                   
                 Max 
                 4.92 
                 3.50 
                 4.92 
                 4.43 
                 4.92 
                 0.684 
               
               
                   
                 n (Samp) 
                 48 
                 14 
                 48 
                 24 
                 48 
                 7 
               
               
                   
                 n (Patient) 
                 44 
                 14 
                 44 
                 24 
                 44 
                 7 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.55 
                 nd 
                 0.44 
                 0.52 
                 nd 
                 0.45 
                 0.40 
                 nd 
                 0.29 
               
               
                 SE 
                 0.084 
                 nd 
                 0.089 
                 0.072 
                 nd 
                 0.073 
                 0.11 
                 nd 
                 0.12 
               
               
                 p 
                 0.57 
                 nd 
                 0.53 
                 0.80 
                 nd 
                 0.45 
                 0.37 
                 nd 
                 0.063 
               
               
                 nCohort 1 
                 53 
                 nd 
                 48 
                 53 
                 nd 
                 48 
                 53 
                 nd 
                 48 
               
               
                 nCohort 2 
                 16 
                 nd 
                 14 
                 24 
                 nd 
                 24 
                 8 
                 nd 
                 7 
               
               
                 Cutoff 1 
                 0.658 
                 nd 
                 0.510 
                 0.540 
                 nd 
                 0.540 
                 0.540 
                 nd 
                 0.540 
               
               
                 Sens 1 
                 75% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 75% 
                 nd 
                 71% 
               
               
                 Spec 1 
                 45% 
                 nd 
                 27% 
                 36% 
                 nd 
                 31% 
                 36% 
                 nd 
                 31% 
               
               
                 Cutoff 2 
                 0.510 
                 nd 
                 0.308 
                 0.340 
                 nd 
                 0.340 
                 0.454 
                 nd 
                 0.454 
               
               
                 Sens 2 
                 81% 
                 nd 
                 86% 
                 83% 
                 nd 
                 83% 
                 88% 
                 nd 
                 86% 
               
               
                 Spec 2 
                 32% 
                 nd 
                  6% 
                 19% 
                 nd 
                 12% 
                 28% 
                 nd 
                 25% 
               
               
                 Cutoff 3 
                 0.183 
                 nd 
                 0.183 
                 0.319 
                 nd 
                 0.308 
                 0.236 
                 nd 
                 0.0870 
               
               
                 Sens 3 
                 94% 
                 nd 
                 93% 
                 92% 
                 nd 
                 92% 
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                  2% 
                 nd 
                  2% 
                 13% 
                 nd 
                  6% 
                  6% 
                 nd 
                  2% 
               
               
                 Cutoff 4 
                 1.22 
                 nd 
                 1.67 
                 1.22 
                 nd 
                 1.67 
                 1.22 
                 nd 
                 1.67 
               
               
                 Sens 4 
                 31% 
                 nd 
                 21% 
                 29% 
                 nd 
                 21% 
                 12% 
                 nd 
                  0% 
               
               
                 Spec 4 
                 72% 
                 nd 
                 71% 
                 72% 
                 nd 
                 71% 
                 72% 
                 nd 
                 71% 
               
               
                 Cutoff 5 
                 1.82 
                 nd 
                 2.14 
                 1.82 
                 nd 
                 2.14 
                 1.82 
                 nd 
                 2.14 
               
               
                 Sens 5 
                 25% 
                 nd 
                 21% 
                 25% 
                 nd 
                 12% 
                 12% 
                 nd 
                  0% 
               
               
                 Spec 5 
                 81% 
                 nd 
                 81% 
                 81% 
                 nd 
                 81% 
                 81% 
                 nd 
                 81% 
               
               
                 Cutoff 6 
                 3.14 
                 nd 
                 3.57 
                 3.14 
                 nd 
                 3.57 
                 3.14 
                 nd 
                 3.57 
               
               
                 Sens 6 
                  6% 
                 nd 
                  0% 
                  8% 
                 nd 
                  4% 
                  0% 
                 nd 
                  0% 
               
               
                 Spec 6 
                 91% 
                 nd 
                 92% 
                 91% 
                 nd 
                 92% 
                 91% 
                 nd 
                 92% 
               
               
                 OR Quart 2 
                 1.4 
                 nd 
                 1.6 
                 1.3 
                 nd 
                 1.3 
                 1.1 
                 nd 
                 &gt;0 
               
               
                 p Value 
                 0.67 
                 nd 
                 0.60 
                 0.72 
                 nd 
                 0.72 
                 0.96 
                 nd 
                 &lt;na   
               
               
                 95% CI of 
                 0.27 
                 nd 
                 0.29 
                 0.32 
                 nd 
                 0.31 
                 0.061 
                 nd 
                 &gt;na   
               
               
                 OR Quart2 
                 7.7 
                 nd 
                 8.6 
                 5.3 
                 nd 
                 5.4 
                 19 
                 nd 
                 na 
               
               
                 OR Quart 3 
                 1.4 
                 nd 
                 1.4 
                 1.6 
                 nd 
                 2.1 
                 7.5 
                 nd 
                 &gt;10 
               
               
                 p Value 
                 0.67 
                 nd 
                 0.67 
                 0.49 
                 nd 
                 0.30 
                 0.085 
                 nd 
                 &lt;0.044 
               
               
                 95% CI of 
                 0.27 
                 nd 
                 0.27 
                 0.41 
                 nd 
                 0.52 
                 0.76 
                 nd 
                 &gt;1.1 
               
               
                 OR Quart3 
                 7.7 
                 nd 
                 7.8 
                 6.5 
                 nd 
                 8.3 
                 74 
                 nd 
                 na 
               
               
                 OR Quart 4 
                 1.8 
                 nd 
                 1.1 
                 1.2 
                 nd 
                 1.0 
                 1.1 
                 nd 
                 &gt;1.2 
               
               
                 p Value 
                 0.48 
                 nd 
                 0.93 
                 0.80 
                 nd 
                 1.0 
                 0.96 
                 nd 
                 &lt;0.92 
               
               
                 95% CI of 
                 0.36 
                 nd 
                 0.18 
                 0.30 
                 nd 
                 0.23 
                 0.061 
                 nd 
                 &gt;0.066 
               
               
                 OR Quart4 
                 9.1 
                 nd 
                 6.4 
                 4.9 
                 nd 
                 4.3 
                 19 
                 nd 
                 na 
               
               
                   
               
            
           
           
               
            
               
                 Carbonic anhydrase IX 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                   
                 24 hr prior to AKI stage 
                   
                 48 hr prior to AKI stage 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
                   
               
            
           
           
               
            
               
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.115 
                 0.121 
                 0.115 
                 0.107 
                 0.115 
                 0.141 
               
               
                   
                 Average 
                 0.155 
                 0.126 
                 0.155 
                 0.209 
                 0.155 
                 0.146 
               
               
                   
                 Stdev 
                 0.139 
                 0.0833 
                 0.139 
                 0.374 
                 0.139 
                 0.0668 
               
               
                   
                 p(t-test) 
                   
                 0.44 
                   
                 0.35 
                   
                 0.86 
               
               
                   
                 Min 
                 0.0145 
                 0.00992 
                 0.0145 
                 0.0142 
                 0.0145 
                 0.0579 
               
               
                   
                 Max 
                 0.796 
                 0.310 
                 0.796 
                 1.90 
                 0.796 
                 0.246 
               
               
                   
                 n (Samp) 
                 55 
                 16 
                 55 
                 24 
                 55 
                 8 
               
               
                   
                 n (Patient) 
                 54 
                 16 
                 54 
                 24 
                 54 
                 8 
               
            
           
           
               
            
               
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 0.124 
                 0.156 
                 0.124 
                 0.117 
                 0.124 
                 0.135 
               
               
                   
                 Average 
                 0.170 
                 0.148 
                 0.170 
                 0.214 
                 0.170 
                 0.134 
               
               
                   
                 Stdev 
                 0.158 
                 0.0908 
                 0.158 
                 0.373 
                 0.158 
                 0.0629 
               
               
                   
                 p(t-test) 
                   
                 0.61 
                   
                 0.48 
                   
                 0.56 
               
               
                   
                 Min 
                 0.0145 
                 0.00992 
                 0.0145 
                 0.0142 
                 0.0145 
                 0.0579 
               
               
                   
                 Max 
                 0.796 
                 0.310 
                 0.796 
                 1.90 
                 0.796 
                 0.246 
               
               
                   
                 n (Samp) 
                 49 
                 14 
                 49 
                 24 
                 49 
                 7 
               
               
                   
                 n (Patient) 
                 45 
                 14 
                 45 
                 24 
                 45 
                 7 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.47 
                 nd 
                 0.51 
                 0.48 
                 nd 
                 0.48 
                 0.57 
                 nd 
                 0.51 
               
               
                 SE 
                 0.083 
                 nd 
                 0.089 
                 0.071 
                 nd 
                 0.073 
                 0.11 
                 nd 
                 0.12 
               
               
                 p 
                 0.72 
                 nd 
                 0.88 
                 0.78 
                 nd 
                 0.76 
                 0.56 
                 nd 
                 0.93 
               
               
                 nCohort 1 
                 55 
                 nd 
                 49 
                 55 
                 nd 
                 49 
                 55 
                 nd 
                 49 
               
               
                 nCohort 2 
                 16 
                 nd 
                 14 
                 24 
                 nd 
                 24 
                 8 
                 nd 
                 7 
               
               
                 Cutoff 1 
                 0.0795 
                 nd 
                 0.0877 
                 0.0780 
                 nd 
                 0.0780 
                 0.0919 
                 nd 
                 0.0901 
               
               
                 Sens 1 
                 75% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 75% 
                 nd 
                 71% 
               
               
                 Spec 1 
                 27% 
                 nd 
                 33% 
                 25% 
                 nd 
                 24% 
                 36% 
                 nd 
                 35% 
               
               
                 Cutoff 2 
                 0.0577 
                 nd 
                 0.0577 
                 0.0665 
                 nd 
                 0.0635 
                 0.0877 
                 nd 
                 0.0877 
               
               
                 Sens 2 
                 81% 
                 nd 
                 86% 
                 83% 
                 nd 
                 83% 
                 88% 
                 nd 
                 86% 
               
               
                 Spec 2 
                 18% 
                 nd 
                 18% 
                 24% 
                 nd 
                 20% 
                 33% 
                 nd 
                 33% 
               
               
                 Cutoff 3 
                 0.0156 
                 nd 
                 0.0156 
                 0.0467 
                 nd 
                 0.0467 
                 0.0577 
                 nd 
                 0.0577 
               
               
                 Sens 3 
                 94% 
                 nd 
                 93% 
                 92% 
                 nd 
                 92% 
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                  4% 
                 nd 
                  4% 
                 15% 
                 nd 
                 12% 
                 18% 
                 nd 
                 18% 
               
               
                 Cutoff 4 
                 0.166 
                 nd 
                 0.212 
                 0.166 
                 nd 
                 0.212 
                 0.166 
                 nd 
                 0.212 
               
               
                 Sens 4 
                 31% 
                 nd 
                 21% 
                 29% 
                 nd 
                 29% 
                 38% 
                 nd 
                 14% 
               
               
                 Spec 4 
                 71% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
                 71% 
                 nd 
                 71% 
               
               
                 Cutoff 5 
                 0.231 
                 nd 
                 0.238 
                 0.231 
                 nd 
                 0.238 
                 0.231 
                 nd 
                 0.238 
               
               
                 Sens 5 
                 12% 
                 nd 
                 21% 
                 29% 
                 nd 
                 25% 
                 12% 
                 nd 
                 14% 
               
               
                 Spec 5 
                 80% 
                 nd 
                 82% 
                 80% 
                 nd 
                 82% 
                 80% 
                 nd 
                 82% 
               
               
                 Cutoff 6 
                 0.325 
                 nd 
                 0.392 
                 0.325 
                 nd 
                 0.392 
                 0.325 
                 nd 
                 0.392 
               
               
                 Sens 6 
                  0% 
                 nd 
                  0% 
                  8% 
                 nd 
                  8% 
                  0% 
                 nd 
                  0% 
               
               
                 Spec 6 
                 91% 
                 nd 
                 92% 
                 91% 
                 nd 
                 92% 
                 91% 
                 nd 
                 92% 
               
               
                 OR Quart 2 
                 1.9 
                 nd 
                 0.92 
                 0.62 
                 nd 
                 0.49 
                 2.0 
                 nd 
                 2.2 
               
               
                 p Value 
                 0.43 
                 nd 
                 0.93 
                 0.49 
                 nd 
                 0.33 
                 0.59 
                 nd 
                 0.55 
               
               
                 95% CI of 
                 0.38 
                 nd 
                 0.16 
                 0.16 
                 nd 
                 0.11 
                 0.16 
                 nd 
                 0.17 
               
               
                 OR Quart2 
                 9.6 
                 nd 
                 5.5 
                 2.4 
                 nd 
                 2.1 
                 25 
                 nd 
                 27 
               
               
                 OR Quart 3 
                 1.4 
                 nd 
                 1.8 
                 1.0 
                 nd 
                 1.1 
                 3.2 
                 nd 
                 3.5 
               
               
                 p Value 
                 0.67 
                 nd 
                 0.48 
                 1.0 
                 nd 
                 0.90 
                 0.34 
                 nd 
                 0.30 
               
               
                 95% CI of 
                 0.27 
                 nd 
                 0.35 
                 0.27 
                 nd 
                 0.29 
                 0.30 
                 nd 
                 0.32 
               
               
                 OR Quart3 
                 7.5 
                 nd 
                 9.5 
                 3.7 
                 nd 
                 4.1 
                 35 
                 nd 
                 39 
               
               
                 OR Quart 4 
                 1.5 
                 nd 
                 0.92 
                 0.66 
                 nd 
                 0.86 
                 2.0 
                 nd 
                 1.0 
               
               
                 p Value 
                 0.61 
                 nd 
                 0.93 
                 0.56 
                 nd 
                 0.82 
                 0.59 
                 nd 
                 1.0 
               
               
                 95% CI of 
                 0.29 
                 nd 
                 0.16 
                 0.17 
                 nd 
                 0.22 
                 0.16 
                 nd 
                 0.056 
               
               
                 OR Quart4 
                 8.2 
                 nd 
                 5.5 
                 2.6 
                 nd 
                 3.3 
                 25 
                 nd 
                 18 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 Comparison of marker levels in EDTA samples collected from 
               
               
                 Cohort 1 (patients that did not progress beyond RIFLE stage 0 or R) and in EDTA 
               
               
                 samples collected from subjects at 0, 24 hours, and 48 hours prior to reaching stage I or F in Cohort 2. 
               
               
                 Beta-2-microglobulin 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 sCr or UO 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 2.35 
                 3.84 
                 2.35 
                 3.30 
                 2.35 
                 3.65 
               
               
                   
                 Average 
                 2.95 
                 4.81 
                 2.95 
                 4.65 
                 2.95 
                 4.18 
               
               
                   
                 Stdev 
                 2.08 
                 3.91 
                 2.08 
                 4.22 
                 2.08 
                 2.85 
               
               
                   
                 p(t-test) 
                   
                 4.1E−5 
                   
                 4.8E−5 
                   
                 0.019 
               
               
                   
                 Min 
                 0.759 
                 0.780 
                 0.759 
                 1.12 
                 0.759 
                 0.945 
               
               
                   
                 Max 
                 16.5 
                 16.7 
                 16.5 
                 22.7 
                 16.5 
                 11.3 
               
               
                   
                 n (Samp) 
                 437 
                 26 
                 437 
                 33 
                 437 
                 17 
               
               
                   
                 n (Patient) 
                 174 
                 26 
                 174 
                 33 
                 174 
                 17 
               
            
           
           
               
               
            
               
                   
                 sCr only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 2.46 
                 6.68 
                 2.46 
                 4.26 
                 2.46 
                 4.60 
               
               
                   
                 Average 
                 3.12 
                 5.93 
                 3.12 
                 7.26 
                 3.12 
                 5.82 
               
               
                   
                 Stdev 
                 2.23 
                 2.51 
                 2.23 
                 7.08 
                 2.23 
                 3.55 
               
               
                   
                 p(t-test) 
                   
                 0.0023 
                   
                 2.9E−7 
                   
                 0.0017 
               
               
                   
                 Min 
                 0.729 
                 2.87 
                 0.729 
                 1.84 
                 0.729 
                 1.90 
               
               
                   
                 Max 
                 16.7 
                 8.27 
                 16.7 
                 22.7 
                 16.7 
                 10.6 
               
               
                   
                 n (Samp) 
                 535 
                 6 
                 535 
                 9 
                 535 
                 7 
               
               
                   
                 n (Patient) 
                 207 
                 6 
                 207 
                 9 
                 207 
                 7 
               
            
           
           
               
               
            
               
                   
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Median 
                 2.41 
                 3.84 
                 2.41 
                 3.30 
                 2.41 
                 3.65 
               
               
                   
                 Average 
                 3.03 
                 4.81 
                 3.03 
                 4.24 
                 3.03 
                 4.32 
               
               
                   
                 Stdev 
                 2.17 
                 3.87 
                 2.17 
                 2.81 
                 2.17 
                 2.90 
               
               
                   
                 p(t-test) 
                   
                 1.7E−4 
                   
                 0.0039 
                   
                 0.019 
               
               
                   
                 Min 
                 0.899 
                 0.780 
                 0.899 
                 1.12 
                 0.899 
                 0.945 
               
               
                   
                 Max 
                 16.5 
                 16.7 
                 16.5 
                 11.9 
                 16.5 
                 11.3 
               
               
                   
                 n (Samp) 
                 362 
                 26 
                 362 
                 31 
                 362 
                 17 
               
               
                   
                 n (Patient) 
                 140 
                 26 
                 140 
                 31 
                 140 
                 17 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.69 
                 0.83 
                 0.69 
                 0.65 
                 0.72 
                 0.65 
                 0.65 
                 0.75 
                 0.66 
               
               
                 SE 
                 0.059 
                 0.10 
                 0.059 
                 0.053 
                 0.097 
                 0.055 
                 0.074 
                 0.11 
                 0.074 
               
               
                 P 
                 0.0014 
                 0.0011 
                 0.0017 
                 0.0052 
                 0.024 
                 0.0056 
                 0.048 
                 0.018 
                 0.033 
               
               
                 nCohort 1 
                 437 
                 535 
                 362 
                 437 
                 535 
                 362 
                 437 
                 535 
                 362 
               
               
                 nCohort 2 
                 26 
                 6 
                 26 
                 33 
                 9 
                 31 
                 17 
                 7 
                 17 
               
               
                 Cutoff 1 
                 2.60 
                 2.93 
                 2.60 
                 2.10 
                 2.27 
                 2.52 
                 2.33 
                 4.35 
                 2.45 
               
               
                 Sens 1 
                 73% 
                 83% 
                 73% 
                 73% 
                 78% 
                 71% 
                 71% 
                 71% 
                 71% 
               
               
                 Spec 1 
                 56% 
                 60% 
                 55% 
                 41% 
                 44% 
                 53% 
                 50% 
                 81% 
                 52% 
               
               
                 Cutoff 2 
                 2.38 
                 2.93 
                 2.38 
                 1.88 
                 1.88 
                 1.96 
                 1.88 
                 2.19 
                 2.27 
               
               
                 Sens 2 
                 81% 
                 83% 
                 81% 
                 82% 
                 89% 
                 81% 
                 82% 
                 86% 
                 82% 
               
               
                 Spec 2 
                 50% 
                 60% 
                 49% 
                 33% 
                 31% 
                 36% 
                 33% 
                 42% 
                 45% 
               
               
                 Cutoff 3 
                 1.47 
                 2.86 
                 1.47 
                 1.56 
                 1.83 
                 1.56 
                 1.43 
                 1.88 
                 1.43 
               
               
                 Sens 3 
                 92% 
                 100%  
                 92% 
                 91% 
                 100%  
                 90% 
                 94% 
                 100%  
                 94% 
               
               
                 Spec 3 
                 18% 
                 59% 
                 18% 
                 22% 
                 30% 
                 21% 
                 16% 
                 31% 
                 17% 
               
               
                 Cutoff 4 
                 3.17 
                 3.47 
                 3.31 
                 3.17 
                 3.47 
                 3.31 
                 3.17 
                 3.47 
                 3.31 
               
               
                 Sens 4 
                 58% 
                 67% 
                 62% 
                 55% 
                 67% 
                 48% 
                 59% 
                 71% 
                 59% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
               
               
                 Cutoff 5 
                 3.83 
                 4.30 
                 3.95 
                 3.83 
                 4.30 
                 3.95 
                 3.83 
                 4.30 
                 3.95 
               
               
                 Sens 5 
                 50% 
                 67% 
                 42% 
                 45% 
                 44% 
                 45% 
                 41% 
                 71% 
                 35% 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
                 80% 
               
               
                 Cutoff 6 
                 5.37 
                 5.58 
                 5.50 
                 5.37 
                 5.58 
                 5.50 
                 5.37 
                 5.58 
                 5.50 
               
               
                 Sens 6 
                 23% 
                 67% 
                 19% 
                 27% 
                 33% 
                 26% 
                 24% 
                 43% 
                 24% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
               
               
                 OR Quart 2 
                 0.99 
                 &gt;0 
                 1.0 
                 2.1 
                 &gt;3.1 
                 1.3 
                 0.99 
                 &gt;2.0 
                 0.65 
               
               
                 p Value 
                 0.99 
                 &lt;na 
                 1.0 
                 0.25 
                 &lt;0.33 
                 0.73 
                 0.99 
                 &lt;0.57 
                 0.64 
               
               
                 95% CI of 
                 0.20 
                 &gt;na 
                 0.20 
                 0.60 
                 &gt;0.32 
                 0.33 
                 0.20 
                 &gt;0.18 
                 0.11 
               
               
                 OR Quart2 
                 5.0 
                 na 
                 5.1 
                 7.0 
                 na 
                 4.9 
                 5.0 
                 na 
                 4.0 
               
               
                 OR Quart 3 
                 2.0 
                 &gt;2.0 
                 1.7 
                 1.3 
                 &gt;0 
                 2.1 
                 0.33 
                 &gt;0 
                 0.99 
               
               
                 p Value 
                 0.32 
                 &lt;0.57 
                 0.47 
                 0.73 
                 &lt;na 
                 0.24 
                 0.34 
                 &lt;na 
                 0.99 
               
               
                 95% CI of 
                 0.50 
                 &gt;0.18 
                 0.40 
                 0.33 
                 &gt;na 
                 0.61 
                 0.034 
                 &gt;na 
                 0.19 
               
               
                 OR Quart3 
                 8.3 
                 na 
                 7.3 
                 4.8 
                 na 
                 7.2 
                 3.2 
                 na 
                 5.0 
               
               
                 OR Quart 4 
                 5.1 
                 &gt;4.1 
                 5.7 
                 4.4 
                 &gt;6.3 
                 3.9 
                 3.5 
                 &gt;5.2 
                 3.2 
               
               
                 p Value 
                 0.012 
                 &lt;0.21 
                 0.0073 
                 0.0097 
                 &lt;0.091 
                 0.021 
                 0.061 
                 &lt;0.14 
                 0.091 
               
               
                 95% CI of 
                 1.4 
                 &gt;0.45 
                 1.6 
                 1.4 
                 &gt;0.75 
                 1.2 
                 0.94 
                 &gt;0.59 
                 0.83 
               
               
                 OR Quart4 
                 18 
                 na 
                 21 
                 14 
                 na 
                 12 
                 13 
                 na 
                 12 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 nd 
                 nd 
                 3740 
                 4690 
                 nd 
                 nd 
               
               
                   
                 Average 
                 nd 
                 nd 
                 4070 
                 6680 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 1650 
                 6470 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.0015 
                 nd 
                 nd 
               
               
                   
                 Min 
                 nd 
                 nd 
                 1120 
                 2100 
                 nd 
                 nd 
               
               
                   
                 Max 
                 nd 
                 nd 
                 10400 
                 23300 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 113 
                 9 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 92 
                 9 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 nd 
                 nd 
                 3980 
                 4690 
                 nd 
                 nd 
               
               
                   
                 Average 
                 nd 
                 nd 
                 4160 
                 6680 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 1700 
                 6470 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.0035 
                 nd 
                 nd 
               
               
                   
                 Min 
                 nd 
                 nd 
                 1120 
                 2100 
                 nd 
                 nd 
               
               
                   
                 Max 
                 nd 
                 nd 
                 10400 
                 23300 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 99 
                 9 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 77 
                 9 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 nd 
                 nd 
                 nd 
                 0.64 
                 nd 
                 0.62 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 nd 
                 nd 
                 nd 
                 0.10 
                 nd 
                 0.10 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 nd 
                 nd 
                 nd 
                 0.17 
                 nd 
                 0.25 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 nd 
                 nd 
                 nd 
                 113 
                 nd 
                 99 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 nd 
                 nd 
                 nd 
                 9 
                 nd 
                 9 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 nd 
                 nd 
                 nd 
                 3620 
                 nd 
                 3580 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 nd 
                 nd 
                 nd 
                 78% 
                 nd 
                 78% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 nd 
                 nd 
                 nd 
                 47% 
                 nd 
                 41% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 nd 
                 nd 
                 nd 
                 3360 
                 nd 
                 3340 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 nd 
                 nd 
                 nd 
                 89% 
                 nd 
                 89% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 nd 
                 nd 
                 nd 
                 41% 
                 nd 
                 38% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 nd 
                 nd 
                 nd 
                 2100 
                 nd 
                 2100 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 nd 
                 nd 
                 nd 
                 100%  
                 nd 
                 100%  
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                 nd 
                 nd 
                 nd 
                  5% 
                 nd 
                  6% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 nd 
                 nd 
                 nd 
                 4690 
                 nd 
                 4900 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 nd 
                 nd 
                 nd 
                 56% 
                 nd 
                 33% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 nd 
                 nd 
                 nd 
                 71% 
                 nd 
                 71% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 nd 
                 nd 
                 nd 
                 5340 
                 nd 
                 5480 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 nd 
                 nd 
                 nd 
                 33% 
                 nd 
                 33% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 nd 
                 nd 
                 nd 
                 81% 
                 nd 
                 81% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 nd 
                 nd 
                 nd 
                 6200 
                 nd 
                 6380 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                 nd 
                 nd 
                 nd 
                 33% 
                 nd 
                 22% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 nd 
                 nd 
                 nd 
                 90% 
                 nd 
                 91% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 nd 
                 nd 
                 nd 
                 2.0 
                 nd 
                 3.2 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 nd 
                 nd 
                 nd 
                 0.58 
                 nd 
                 0.32 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 nd 
                 nd 
                 nd 
                 0.17 
                 nd 
                 0.32 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 nd 
                 nd 
                 nd 
                 23 
                 nd 
                 33 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 nd 
                 nd 
                 nd 
                 3.2 
                 nd 
                 2.1 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 nd 
                 nd 
                 nd 
                 0.32 
                 nd 
                 0.56 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 nd 
                 nd 
                 nd 
                 0.32 
                 nd 
                 0.18 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 nd 
                 nd 
                 nd 
                 33 
                 nd 
                 24 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 nd 
                 nd 
                 nd 
                 3.1 
                 nd 
                 3.2 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 nd 
                 nd 
                 nd 
                 0.34 
                 nd 
                 0.32 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 nd 
                 nd 
                 nd 
                 0.30 
                 nd 
                 0.32 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 nd 
                 nd 
                 nd 
                 32 
                 nd 
                 33 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 Comparison of the maximum marker levels in EDTA samples 
               
               
                 collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0) and the 
               
               
                 maximum values in EDTA samples collected from subjects between enrollment and 0, 24 
               
               
                 hours, and 48 hours prior to reaching stage F in Cohort 2. 
               
               
                 Beta-2-microglobulin 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 2.63 
                 7.26 
                 2.63 
                 6.24 
                 2.63 
                 5.57 
               
               
                   
                 Average 
                 3.24 
                 8.21 
                 3.24 
                 7.37 
                 3.24 
                 5.98 
               
               
                   
                 Stdev 
                 2.18 
                 5.22 
                 2.18 
                 5.28 
                 2.18 
                 3.16 
               
               
                   
                 p(t-test) 
                   
                 3.7E−10 
                   
                 1.1E−7 
                   
                 0.0012 
               
               
                   
                 Min 
                 0.951 
                 2.40 
                 0.951 
                 2.19 
                 0.951 
                 2.34 
               
               
                   
                 Max 
                 12.1 
                 22.7 
                 12.1 
                 22.7 
                 12.1 
                 11.3 
               
               
                   
                 n (Samp) 
                 111 
                 16 
                 111 
                 16 
                 111 
                 8 
               
               
                   
                 n (Patient) 
                 111 
                 16 
                 111 
                 16 
                 111 
                 8 
               
               
                   
                 sCr only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 2.62 
                 8.11 
                 2.62 
                 6.44 
                 nd 
                 nd 
               
               
                   
                 Average 
                 3.34 
                 9.20 
                 3.34 
                 8.54 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 2.33 
                 6.94 
                 2.33 
                 7.37 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 5.7E−9 
                   
                 2.7E−7 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.951 
                 2.40 
                 0.951 
                 2.19 
                 nd 
                 nd 
               
               
                   
                 Max 
                 16.7 
                 22.7 
                 16.7 
                 22.7 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 180 
                 8 
                 180 
                 8 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 180 
                 8 
                 180 
                 8 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 2.66 
                 7.62 
                 2.66 
                 6.90 
                 2.66 
                 5.57 
               
               
                   
                 Average 
                 3.09 
                 8.36 
                 3.09 
                 7.55 
                 3.09 
                 6.46 
               
               
                   
                 Stdev 
                 1.97 
                 3.54 
                 1.97 
                 3.23 
                 1.97 
                 3.33 
               
               
                   
                 p(t-test) 
                   
                 6.8E−11 
                   
                 7.4E−9 
                   
                 2.0E−4 
               
               
                   
                 Min 
                 0.951 
                 3.32 
                 0.951 
                 2.34 
                 0.951 
                 2.34 
               
               
                   
                 Max 
                 12.1 
                 14.6 
                 12.1 
                 11.9 
                 12.1 
                 11.3 
               
               
                   
                 n (Samp) 
                 91 
                 10 
                 91 
                 10 
                 91 
                 6 
               
               
                   
                 n (Patient) 
                 91 
                 10 
                 91 
                 10 
                 91 
                 6 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.86 
                 0.82 
                 0.93 
                 0.80 
                 0.74 
                 0.89 
                 0.79 
                 nd 
                 0.83 
               
               
                 SE 
                 0.060 
                 0.092 
                 0.058 
                 0.069 
                 0.10 
                 0.069 
                 0.098 
                 nd 
                 0.11 
               
               
                 p 
                 1.6E−9 
                 4.2E−4 
                 1.5E−13 
                 1.5E−5 
                 0.018 
                 2.2E−8 
                 0.0035 
                 nd 
                 0.0018 
               
               
                 nCohort 1 
                 111 
                 180 
                 91 
                 111 
                 180 
                 91 
                 111 
                 nd 
                 91 
               
               
                 nCohort 2 
                 16 
                 8 
                 10 
                 16 
                 8 
                 10 
                 8 
                 nd 
                 6 
               
               
                 Cutoff 1 
                 4.35 
                 3.32 
                 6.82 
                 4.16 
                 2.38 
                 5.62 
                 4.35 
                 nd 
                 4.35 
               
               
                 Sens 1 
                 75% 
                 75% 
                 70% 
                 75% 
                 75% 
                 70% 
                 75% 
                 nd 
                 83% 
               
               
                 Spec 1 
                 77% 
                 66% 
                 97% 
                 76% 
                 44% 
                 88% 
                 77% 
                 nd 
                 81% 
               
               
                 Cutoff 2 
                 3.32 
                 2.93 
                 5.62 
                 2.38 
                 2.27 
                 5.39 
                 2.38 
                 nd 
                 4.35 
               
               
                 Sens 2 
                 81% 
                 88% 
                 80% 
                 81% 
                 88% 
                 80% 
                 88% 
                 nd 
                 83% 
               
               
                 Spec 2 
                 67% 
                 57% 
                 88% 
                 46% 
                 41% 
                 87% 
                 46% 
                 nd 
                 81% 
               
               
                 Cutoff 3 
                 2.93 
                 2.38 
                 4.35 
                 2.26 
                 2.17 
                 4.35 
                 2.30 
                 nd 
                 2.30 
               
               
                 Sens 3 
                 94% 
                 100%  
                 90% 
                 94% 
                 100%  
                 90% 
                 100%  
                 nd 
                 100%  
               
               
                 Spec 3 
                 59% 
                 44% 
                 81% 
                 42% 
                 37% 
                 81% 
                 44% 
                 nd 
                 43% 
               
               
                 Cutoff 4 
                 3.61 
                 3.62 
                 3.43 
                 3.61 
                 3.62 
                 3.43 
                 3.61 
                 nd 
                 3.43 
               
               
                 Sens 4 
                 75% 
                 62% 
                 90% 
                 75% 
                 62% 
                 90% 
                 75% 
                 nd 
                 83% 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 70% 
                 nd 
                 70% 
               
               
                 Cutoff 5 
                 4.76 
                 4.76 
                 4.31 
                 4.76 
                 4.76 
                 4.31 
                 4.76 
                 nd 
                 4.31 
               
               
                 Sens 5 
                 69% 
                 62% 
                 90% 
                 62% 
                 50% 
                 90% 
                 62% 
                 nd 
                 83% 
               
               
                 Spec 5 
                 81% 
                 80% 
                 80% 
                 81% 
                 80% 
                 80% 
                 81% 
                 nd 
                 80% 
               
               
                 Cutoff 6 
                 6.14 
                 6.17 
                 6.04 
                 6.14 
                 6.17 
                 6.04 
                 6.14 
                 nd 
                 6.04 
               
               
                 Sens 6 
                 62% 
                 62% 
                 70% 
                 50% 
                 50% 
                 60% 
                 38% 
                 nd 
                 33% 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 90% 
                 nd 
                 90% 
               
               
                 OR Quart 2 
                 &gt;1.0 
                 &gt;1.0 
                 &gt;0 
                 &gt;4.4 
                 &gt;3.2 
                 &gt;1.0 
                 &gt;2.1 
                 nd 
                 &gt;1.0 
               
               
                 p Value 
                 &lt;1.0 
                 &lt;0.99 
                 &lt;na 
                 &lt;0.19 
                 &lt;0.32 
                 &lt;0.98 
                 &lt;0.56 
                 nd 
                 &lt;0.98 
               
               
                 95% CI of 
                 &gt;0.060 
                 &gt;0.062 
                 &gt;na 
                 &gt;0.47 
                 &gt;0.32 
                 &gt;0.062 
                 &gt;0.18 
                 nd 
                 &gt;0.062 
               
               
                 OR Quart2 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                 OR Quart 3 
                 &gt;4.4 
                 &gt;2.1 
                 &gt;1.0 
                 &gt;2.1 
                 &gt;1.0 
                 &gt;0 
                 &gt;1.0 
                 nd 
                 &gt;0 
               
               
                 p Value 
                 &lt;0.19 
                 &lt;0.55 
                 &lt;0.98 
                 &lt;0.56 
                 &lt;0.99 
                 &lt;na 
                 &lt;1.0 
                 nd 
                 &lt;na 
               
               
                 95% CI of 
                 &gt;0.47 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;0.18 
                 &gt;0.062 
                 &gt;na 
                 &gt;0.060 
                 nd 
                 &gt;na 
               
               
                 OR Quart3 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                 OR Quart 4 
                 &gt;16 
                 &gt;5.6 
                 &gt;13 
                 &gt;14 
                 &gt;4.4 
                 &gt;13 
                 &gt;5.8 
                 nd 
                 &gt;6.0 
               
               
                 p Value 
                 &lt;0.0100 
                 &lt;0.12 
                 &lt;0.019 
                 &lt;0.015 
                 &lt;0.19 
                 &lt;0.019 
                 &lt;0.12 
                 nd 
                 &lt;0.11 
               
               
                 95% CI of 
                 &gt;1.9 
                 &gt;0.63 
                 &gt;1.5 
                 &gt;1.7 
                 &gt;0.47 
                 &gt;1.5 
                 &gt;0.63 
                 nd 
                 &gt;0.65 
               
               
                 OR Quart4 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 Comparison of marker levels in urine samples collected from Cohort 
               
               
                 1 (patients that did not progress beyond RIFLE stage 0, R, or I) and in urine samples 
               
               
                 collected from Cohort 2 (subjects who progress to RIFLE stage F) at 0, 24 hours, and 48 
               
               
                 hours prior to the subject reaching RIFLE stage I. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 1.51 
                 0.990 
                 1.51 
                 0.202 
                 nd 
                 nd 
               
               
                   
                 Average 
                 2.57 
                 2.02 
                 2.57 
                 1.80 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 2.44 
                 2.22 
                 2.44 
                 2.59 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.48 
                   
                 0.30 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.00152 
                 0.00133 
                 0.00152 
                 0.00212 
                 nd 
                 nd 
               
               
                   
                 Max 
                 6.10 
                 5.64 
                 6.10 
                 5.80 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 534 
                 10 
                 534 
                 11 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 204 
                 10 
                 204 
                 11 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 1.60 
                 0.480 
                 1.60 
                 0.163 
                 nd 
                 nd 
               
               
                   
                 Average 
                 2.61 
                 1.86 
                 2.61 
                 0.998 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 2.44 
                 2.11 
                 2.44 
                 1.98 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.42 
                   
                 0.064 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.00152 
                 0.00403 
                 0.00152 
                 0.00212 
                 nd 
                 nd 
               
               
                   
                 Max 
                 6.10 
                 4.76 
                 6.10 
                 5.80 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 454 
                 7 
                 454 
                 8 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 168 
                 7 
                 168 
                 8 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.40 
                 nd 
                 0.38 
                 0.40 
                 nd 
                 0.29 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.096 
                 nd 
                 0.11 
                 0.091 
                 nd 
                 0.10 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 0.29 
                 nd 
                 0.31 
                 0.25 
                 nd 
                 0.044 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 534 
                 nd 
                 454 
                 534 
                 nd 
                 454 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 10 
                 nd 
                 7 
                 11 
                 nd 
                 8 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 0.260 
                 nd 
                 0.214 
                 0.153 
                 nd 
                 0.0999 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 70% 
                 nd 
                 71% 
                 73% 
                 nd 
                 75% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 28% 
                 nd 
                 25% 
                 22% 
                 nd 
                 17% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 0.0899 
                 nd 
                 0.0899 
                 0.100 
                 nd 
                 0.0301 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 80% 
                 nd 
                 86% 
                 82% 
                 nd 
                 88% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 17% 
                 nd 
                 16% 
                 18% 
                 nd 
                  7% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 0.00347 
                 nd 
                 0.00347 
                 0.0319 
                 nd 
                 0.00181 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 90% 
                 nd 
                 100%  
                 91% 
                 nd 
                 100%  
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                  1% 
                 nd 
                  1% 
                  7% 
                 nd 
                  0% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 5.13 
                 nd 
                 5.20 
                 5.13 
                 nd 
                 5.20 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 10% 
                 nd 
                  0% 
                 27% 
                 nd 
                 12% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 70% 
                 nd 
                 70% 
                 70% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 5.80 
                 nd 
                 5.80 
                 5.80 
                 nd 
                 5.80 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                  0% 
                 nd 
                  0% 
                  0% 
                 nd 
                  0% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 95% 
                 nd 
                 94% 
                 95% 
                 nd 
                 94% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 5.80 
                 nd 
                 5.80 
                 5.80 
                 nd 
                 5.80 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                  0% 
                 nd 
                  0% 
                  0% 
                 nd 
                  0% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 95% 
                 nd 
                 94% 
                 95% 
                 nd 
                 94% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 &gt;5.2 
                 nd 
                 &gt;3.1 
                 0 
                 nd 
                 0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 &lt;0.14 
                 nd 
                 &lt;0.33 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 &gt;0.60 
                 nd 
                 &gt;0.32 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 &gt;2.0 
                 nd 
                 &gt;1.0 
                 1.0 
                 nd 
                 2.0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 &lt;0.57 
                 nd 
                 &lt;0.99 
                 0.99 
                 nd 
                 0.57 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 &gt;0.18 
                 nd 
                 &gt;0.063 
                 0.20 
                 nd 
                 0.18 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 na 
                 nd 
                 na 
                 5.1 
                 nd 
                 23 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 &gt;3.1 
                 nd 
                 &gt;3.1 
                 1.7 
                 nd 
                 5.2 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 &lt;0.33 
                 nd 
                 &lt;0.33 
                 0.47 
                 nd 
                 0.13 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 &gt;0.32 
                 nd 
                 &gt;0.32 
                 0.40 
                 nd 
                 0.60 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 na 
                 nd 
                 na 
                 7.3 
                 nd 
                 45 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
            
               
                 C-X-C motif chemokine 2 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 0.689 
                 11.6 
                 0.689 
                 27.9 
                 0.689 
                 3.59 
               
               
                   
                 Average 
                 8.05 
                 33.9 
                 8.05 
                 45.6 
                 8.05 
                 7.16 
               
               
                   
                 Stdev 
                 22.2 
                 60.3 
                 22.2 
                 62.5 
                 22.2 
                 8.31 
               
               
                   
                 p(t-test) 
                   
                 6.7E−5 
                   
                 3.2E−10 
                   
                 0.92 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.534 
                 0.00804 
                 0.0260 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 18.5 
               
               
                   
                 n (Samp) 
                 932 
                 13 
                 932 
                 16 
                 932 
                 7 
               
               
                   
                 n (Patient) 
                 343 
                 13 
                 343 
                 16 
                 343 
                 7 
               
               
                   
                 sCr only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 0.895 
                 27.8 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 Average 
                 8.75 
                 52.6 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 23.4 
                 76.5 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 2.0E−6 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 Max 
                 266 
                 217 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 969 
                 7 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 353 
                 7 
                 nd 
                 nd 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 0.805 
                 9.01 
                 0.805 
                 28.6 
                 nd 
                 nd 
               
               
                   
                 Average 
                 8.30 
                 46.4 
                 8.30 
                 49.6 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 22.4 
                 75.1 
                 22.4 
                 66.0 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 4.9E−6 
                   
                 1.8E−10 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.534 
                 nd 
                 nd 
               
               
                   
                 Max 
                 266 
                 217 
                 266 
                 217 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 797 
                 8 
                 797 
                 14 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 260 
                 8 
                 260 
                 14 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24hr 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 
                 0.63 
                 0.73 
                 0.62 
                 0.83 
                 nd 
                 0.82 
                 0.59 
                 nd 
                 nd 
               
               
                 SE 
                 0.084 
                 0.11 
                 0.11 
                 0.064 
                 nd 
                 0.069 
                 0.11 
                 nd 
                 nd 
               
               
                 p 
                 0.13 
                 0.039 
                 0.25 
                 2.1E−7 
                 nd 
                 2.6E−6 
                 0.44 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 932 
                 969 
                 797 
                 932 
                 nd 
                 797 
                 932 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 13 
                 7 
                 8 
                 16 
                 nd 
                 14 
                 7 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 0.00804 
                 11.6 
                 0.00804 
                 6.36 
                 nd 
                 11.6 
                 0.135 
                 nd 
                 nd 
               
               
                 Sens 1 
                 100%  
                 71% 
                 100%  
                 75% 
                 nd 
                 71% 
                 71% 
                 nd 
                 nd 
               
               
                 Spec 1 
                  0% 
                 82% 
                  0% 
                 75% 
                 nd 
                 83% 
                 43% 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 0.00804 
                 0.00804 
                 0.00804 
                 1.64 
                 nd 
                 1.54 
                 0.00804 
                 nd 
                 nd 
               
               
                 Sens 2 
                 100%  
                 100%  
                 100%  
                 81% 
                 nd 
                 86% 
                 100%  
                 nd 
                 nd 
               
               
                 Spec 2 
                  0% 
                  0% 
                  0% 
                 56% 
                 nd 
                 54% 
                  0% 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 0.00804 
                 0.00804 
                 0.00804 
                 1.45 
                 nd 
                 1.45 
                 0.00804 
                 nd 
                 nd 
               
               
                 Sens 3 
                 100%  
                 100%  
                 100%  
                 94% 
                 nd 
                 93% 
                 100%  
                 nd 
                 nd 
               
               
                 Spec 3 
                  0% 
                  0% 
                  0% 
                 54% 
                 nd 
                 53% 
                  0% 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 4.46 
                 5.17 
                 4.82 
                 4.46 
                 nd 
                 4.82 
                 4.46 
                 nd 
                 nd 
               
               
                 Sens 4 
                 54% 
                 71% 
                 50% 
                 75% 
                 nd 
                 71% 
                 43% 
                 nd 
                 nd 
               
               
                 Spec 4 
                 70% 
                 70% 
                 70% 
                 70% 
                 nd 
                 70% 
                 70% 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 8.41 
                 9.64 
                 8.68 
                 8.41 
                 nd 
                 8.68 
                 8.41 
                 nd 
                 nd 
               
               
                 Sens 5 
                 54% 
                 71% 
                 50% 
                 69% 
                 nd 
                 71% 
                 43% 
                 nd 
                 nd 
               
               
                 Spec 5 
                 80% 
                 80% 
                 80% 
                 80% 
                 nd 
                 80% 
                 80% 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 19.3 
                 20.9 
                 20.1 
                 19.3 
                 nd 
                 20.1 
                 19.3 
                 nd 
                 nd 
               
               
                 Sens 6 
                 38% 
                 57% 
                 38% 
                 62% 
                 nd 
                 64% 
                  0% 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 90% 
                 90% 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 0 
                 &gt;2.0 
                 &gt;3.0 
                 &gt;1.0 
                 nd 
                 &gt;1.0 
                 0.50 
                 nd 
                 nd 
               
               
                 p Value 
                 na 
                 &lt;0.57 
                 &lt;0.34 
                 &lt;1.00 
                 nd 
                 &lt;1.0 
                 0.57 
                 nd 
                 nd 
               
               
                 95% CI of 
                 na 
                 &gt;0.18 
                 &gt;0.31 
                 &gt;0.062 
                 nd 
                 &gt;0.062 
                 0.045 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 na 
                 na 
                 na 
                 na 
                 nd 
                 na 
                 5.5 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 0.20 
                 &gt;0 
                 &gt;1.0 
                 &gt;4.1 
                 nd 
                 &gt;3.0 
                 0.50 
                 nd 
                 nd 
               
               
                 p Value 
                 0.14 
                 &lt;na 
                 &lt;1.00 
                 &lt;0.21 
                 nd 
                 &lt;0.34 
                 0.57 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.023 
                 &gt;na 
                 &gt;0.062 
                 &gt;0.45 
                 nd 
                 &gt;0.31 
                 0.045 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 1.7 
                 na 
                 na 
                 na 
                 nd 
                 na 
                 5.5 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 1.4 
                 &gt;5.1 
                 &gt;4.1 
                 &gt;12 
                 nd 
                 &gt;10 
                 1.5 
                 nd 
                 nd 
               
               
                 p Value 
                 0.57 
                 &lt;0.14 
                 &lt;0.21 
                 &lt;0.020 
                 nd 
                 &lt;0.026 
                 0.66 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.44 
                 &gt;0.59 
                 &gt;0.45 
                 &gt;1.5 
                 nd 
                 &gt;1.3 
                 0.25 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 4.5 
                 na 
                 na 
                 na 
                 nd 
                 na 
                 9.1 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 384 
                 670 
                 384 
                 3140 
                 nd 
                 nd 
               
               
                   
                 Average 
                 850 
                 1270 
                 850 
                 4360 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 1270 
                 1520 
                 1270 
                 6140 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.39 
                   
                 6.2E−11 
                 nd 
                 nd 
               
               
                   
                 Min 
                 1.00E−9 
                 78.9 
                 1.00E−9 
                 226 
                 nd 
                 nd 
               
               
                   
                 Max 
                 9810 
                 4050 
                 9810 
                 21100 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 322 
                 7 
                 322 
                 10 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 188 
                 7 
                 188 
                 10 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 nd 
                 nd 
                 396 
                 3330 
                 nd 
                 nd 
               
               
                   
                 Average 
                 nd 
                 nd 
                 905 
                 4940 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 1320 
                 6790 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 1.3E−10 
                 nd 
                 nd 
               
               
                   
                 Min 
                 nd 
                 nd 
                 1.00E−9 
                 226 
                 nd 
                 nd 
               
               
                   
                 Max 
                 nd 
                 nd 
                 9810 
                 21100 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 280 
                 8 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 157 
                 8 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 0.60 
                 nd 
                 nd 
                 0.82 
                 nd 
                 0.81 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.11 
                 nd 
                 nd 
                 0.083 
                 nd 
                 0.093 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 0.38 
                 nd 
                 nd 
                 1.3E−4 
                 nd 
                 8.4E−4 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 322 
                 nd 
                 nd 
                 322 
                 nd 
                 280 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 7 
                 nd 
                 nd 
                 10 
                 nd 
                 8 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 310 
                 nd 
                 nd 
                 1480 
                 nd 
                 1480 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 71% 
                 nd 
                 nd 
                 70% 
                 nd 
                 75% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 46% 
                 nd 
                 nd 
                 81% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 97.3 
                 nd 
                 nd 
                 667 
                 nd 
                 407 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 86% 
                 nd 
                 nd 
                 80% 
                 nd 
                 88% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 24% 
                 nd 
                 nd 
                 66% 
                 nd 
                 51% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 69.5 
                 nd 
                 nd 
                 407 
                 nd 
                 225 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 100%  
                 nd 
                 nd 
                 90% 
                 nd 
                 100%  
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                 22% 
                 nd 
                 nd 
                 53% 
                 nd 
                 34% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 804 
                 nd 
                 nd 
                 804 
                 nd 
                 865 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 43% 
                 nd 
                 nd 
                 70% 
                 nd 
                 75% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 70% 
                 nd 
                 nd 
                 70% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 1440 
                 nd 
                 nd 
                 1440 
                 nd 
                 1520 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 29% 
                 nd 
                 nd 
                 70% 
                 nd 
                 62% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 80% 
                 nd 
                 nd 
                 80% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 2280 
                 nd 
                 nd 
                 2280 
                 nd 
                 2350 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                 29% 
                 nd 
                 nd 
                 60% 
                 nd 
                 62% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 nd 
                 90% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 0.49 
                 nd 
                 nd 
                 &gt;1.0 
                 nd 
                 &gt;2.1 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.57 
                 nd 
                 nd 
                 &lt;0.99 
                 nd 
                 &lt;0.56 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.044 
                 nd 
                 nd 
                 &gt;0.062 
                 nd 
                 &gt;0.18 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 5.6 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 1.0 
                 nd 
                 nd 
                 &gt;2.0 
                 nd 
                 &gt;0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 1.0 
                 nd 
                 nd 
                 &lt;0.56 
                 nd 
                 &lt;na 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.14 
                 nd 
                 nd 
                 &gt;0.18 
                 nd 
                 &gt;na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 7.3 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 0.99 
                 nd 
                 nd 
                 &gt;7.6 
                 nd 
                 &gt;6.5 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.99 
                 nd 
                 nd 
                 &lt;0.060 
                 nd 
                 &lt;0.086 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.14 
                 nd 
                 nd 
                 &gt;0.92 
                 nd 
                 &gt;0.77 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 7.2 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
            
               
                 Cathepsin B 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 0.632 
                 1.86 
                 0.632 
                 2.76 
                 nd 
                 nd 
               
               
                   
                 Average 
                 2.59 
                 3.31 
                 2.59 
                 13.5 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 8.00 
                 4.58 
                 8.00 
                 20.9 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.81 
                   
                  9.4E−5 
                 nd 
                 nd 
               
               
                   
                 Min 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 1.00E−9 
                 nd 
                 nd 
               
               
                   
                 Max 
                 78.1 
                 12.7 
                 78.1 
                 64.9 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 339 
                 7 
                 339 
                 10 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 194 
                 7 
                 194 
                 10 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 nd 
                 nd 
                 0.726 
                 2.35 
                 nd 
                 nd 
               
               
                   
                 Average 
                 nd 
                 nd 
                 2.90 
                 13.5 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 8.59 
                 23.0 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.0014 
                 nd 
                 nd 
               
               
                   
                 Min 
                 nd 
                 nd 
                 1.00E−9 
                 1.00E−9 
                 nd 
                 nd 
               
               
                   
                 Max 
                 nd 
                 nd 
                 78.1 
                 64.9 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 295 
                 8 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 162 
                 8 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 nd 
                 nd 
                 0.75 
                 nd 
                 0.70 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.11 
                 nd 
                 nd 
                 0.091 
                 nd 
                 0.11 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 0.51 
                 nd 
                 nd 
                 0.0065 
                 nd 
                 0.059 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 339 
                 nd 
                 nd 
                 339 
                 nd 
                 295 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 7 
                 nd 
                 nd 
                 10 
                 nd 
                 8 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 0.397 
                 nd 
                 nd 
                 1.39 
                 nd 
                 0.973 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 71% 
                 nd 
                 nd 
                 70% 
                 nd 
                 75% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 38% 
                 nd 
                 nd 
                 70% 
                 nd 
                 58% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 0.0840 
                 nd 
                 nd 
                 0.973 
                 nd 
                 0.924 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 86% 
                 nd 
                 nd 
                 80% 
                 nd 
                 88% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 15% 
                 nd 
                 nd 
                 60% 
                 nd 
                 57% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 0 
                 nd 
                 nd 
                 0.924 
                 nd 
                 0 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 100%  
                 nd 
                 nd 
                 90% 
                 nd 
                 100%  
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                  0% 
                 nd 
                 nd 
                 59% 
                 nd 
                  0% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 1.41 
                 nd 
                 nd 
                 1.41 
                 nd 
                 1.57 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 57% 
                 nd 
                 nd 
                 60% 
                 nd 
                 50% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 70% 
                 nd 
                 nd 
                 70% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 2.48 
                 nd 
                 nd 
                 2.48 
                 nd 
                 2.74 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 43% 
                 nd 
                 nd 
                 50% 
                 nd 
                 50% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 80% 
                 nd 
                 nd 
                 80% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 5.07 
                 nd 
                 nd 
                 5.07 
                 nd 
                 5.47 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                 29% 
                 nd 
                 nd 
                 40% 
                 nd 
                 38% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 nd 
                 90% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 0.49 
                 nd 
                 nd 
                 0 
                 nd 
                 0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.56 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.043 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 5.5 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 0.49 
                 nd 
                 nd 
                 3.1 
                 nd 
                 3.0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.57 
                 nd 
                 nd 
                 0.34 
                 nd 
                 0.34 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.044 
                 nd 
                 nd 
                 0.31 
                 nd 
                 0.31 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 5.6 
                 nd 
                 nd 
                 30 
                 nd 
                 30 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 1.5 
                 nd 
                 nd 
                 6.3 
                 nd 
                 4.1 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.66 
                 nd 
                 nd 
                 0.092 
                 nd 
                 0.21 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.24 
                 nd 
                 nd 
                 0.74 
                 nd 
                 0.45 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 9.2 
                 nd 
                 nd 
                 53 
                 nd 
                 38 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
            
               
                 Dipeptidyl peptidase IV 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 197 
                 1310 
                 197 
                 1010 
                 nd 
                 nd 
               
               
                   
                 Average 
                 3440 
                 2090 
                 3440 
                 2020 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 42400 
                 2430 
                 42400 
                 2600 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 0.94 
                   
                 0.92 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.200 
                 0.651 
                 0.200 
                 10.1 
                 nd 
                 nd 
               
               
                   
                 Max 
                 677000 
                 5420 
                 677000 
                 7150 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 255 
                 6 
                 255 
                 8 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 158 
                 6 
                 158 
                 8 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 nd 
                 nd 
                 197 
                 847 
                 nd 
                 nd 
               
               
                   
                 Average 
                 nd 
                 nd 
                 706 
                 1390 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 nd 
                 nd 
                 1510 
                 1830 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                 nd 
                 nd 
                   
                 0.28 
                 nd 
                 nd 
               
               
                   
                 Min 
                 nd 
                 nd 
                 0.200 
                 10.1 
                 nd 
                 nd 
               
               
                   
                 Max 
                 nd 
                 nd 
                 12500 
                 4950 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 nd 
                 nd 
                 221 
                 6 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 nd 
                 nd 
                 134 
                 6 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 nd 
                 nd 
                 0.71 
                 nd 
                 0.67 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.12 
                 nd 
                 nd 
                 0.10 
                 nd 
                 0.12 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 0.49 
                 nd 
                 nd 
                 0.049 
                 nd 
                 0.18 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 255 
                 nd 
                 nd 
                 255 
                 nd 
                 221 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 6 
                 nd 
                 nd 
                 8 
                 nd 
                 6 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 52.3 
                 nd 
                 nd 
                 337 
                 nd 
                 294 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 83% 
                 nd 
                 nd 
                 75% 
                 nd 
                 83% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 29% 
                 nd 
                 nd 
                 58% 
                 nd 
                 57% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 52.3 
                 nd 
                 nd 
                 294 
                 nd 
                 294 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 83% 
                 nd 
                 nd 
                 88% 
                 nd 
                 83% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 29% 
                 nd 
                 nd 
                 56% 
                 nd 
                 57% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 0.202 
                 nd 
                 nd 
                 9.55 
                 nd 
                 9.55 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 100%  
                 nd 
                 nd 
                 100%  
                 nd 
                 100%  
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                  1% 
                 nd 
                 nd 
                 11% 
                 nd 
                 12% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 623 
                 nd 
                 nd 
                 623 
                 nd 
                 623 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 50% 
                 nd 
                 nd 
                 62% 
                 nd 
                 50% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 70% 
                 nd 
                 nd 
                 70% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 1020 
                 nd 
                 nd 
                 1020 
                 nd 
                 942 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 50% 
                 nd 
                 nd 
                 50% 
                 nd 
                 50% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 80% 
                 nd 
                 nd 
                 80% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 1810 
                 nd 
                 nd 
                 1810 
                 nd 
                 1580 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                 50% 
                 nd 
                 nd 
                 25% 
                 nd 
                 17% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 nd 
                 90% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 2.0 
                 nd 
                 nd 
                 0 
                 nd 
                 0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.57 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.18 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 23 
                 nd 
                 nd 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 0 
                 nd 
                 nd 
                 3.0 
                 nd 
                 2.0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 na 
                 nd 
                 nd 
                 0.34 
                 nd 
                 0.58 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 na 
                 nd 
                 nd 
                 0.31 
                 nd 
                 0.18 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 na 
                 nd 
                 nd 
                 30 
                 nd 
                 23 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 3.0 
                 nd 
                 nd 
                 4.1 
                 nd 
                 3.1 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 0.34 
                 nd 
                 nd 
                 0.21 
                 nd 
                 0.34 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 0.31 
                 nd 
                 nd 
                 0.45 
                 nd 
                 0.31 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 30 
                 nd 
                 nd 
                 38 
                 nd 
                 30 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 Comparison of marker levels in EDTA samples collected from Cohort 1 (patients that did not progress beyond RIFLE 
               
               
                 stage 0, R, or I) and in EDTA samples collected from Cohort 2 (subjects who progress to RIFLE stage F) at 0, 24 hours, 
               
               
                 and 48 hours prior to the subject reaching RIFLE stage I. 
               
               
                 Beta-2-microglobulin 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 0 hr prior to AKI stage 
                 24 hr prior to AKI stage 
                 48 hr prior to AKI stage 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                   
                 sCr or UO 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 2.46 
                 5.00 
                 2.46 
                 5.64 
                 nd 
                 nd 
               
               
                   
                 Average 
                 3.12 
                 6.46 
                 3.12 
                 7.49 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 2.19 
                 3.84 
                 2.19 
                 6.07 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 3.9E−7 
                   
                 1.0E−9 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.729 
                 2.19 
                 0.729 
                 1.52 
                 nd 
                 nd 
               
               
                   
                 Max 
                 16.7 
                 14.6 
                 16.7 
                 22.7 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 551 
                 12 
                 551 
                 11 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 213 
                 12 
                 213 
                 11 
                 nd 
                 nd 
               
               
                   
                 UO only 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Median 
                 2.54 
                 6.19 
                 2.54 
                 5.64 
                 nd 
                 nd 
               
               
                   
                 Average 
                 3.15 
                 7.19 
                 3.15 
                 6.53 
                 nd 
                 nd 
               
               
                   
                 Stdev 
                 2.22 
                 3.93 
                 2.22 
                 3.65 
                 nd 
                 nd 
               
               
                   
                 p(t-test) 
                   
                 7.7E−7 
                   
                 1.1E−5 
                 nd 
                 nd 
               
               
                   
                 Min 
                 0.729 
                 3.32 
                 0.729 
                 1.52 
                 nd 
                 nd 
               
               
                   
                 Max 
                 16.7 
                 14.6 
                 16.7 
                 11.9 
                 nd 
                 nd 
               
               
                   
                 n (Samp) 
                 464 
                 8 
                 464 
                 9 
                 nd 
                 nd 
               
               
                   
                 n (Patient) 
                 173 
                 8 
                 173 
                 9 
                 nd 
                 nd 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 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 
                 nd 
                 0.88 
                 0.78 
                 nd 
                 0.79 
                 nd 
                 nd 
                 nd 
               
               
                 SE 
                 0.075 
                 nd 
                 0.079 
                 0.083 
                 nd 
                 0.090 
                 nd 
                 nd 
                 nd 
               
               
                 p 
                 1.7E−5 
                 nd 
                 1.8E−6 
                 6.7E−4 
                 nd 
                 0.0011 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 1 
                 551 
                 nd 
                 464 
                 551 
                 nd 
                 464 
                 nd 
                 nd 
                 nd 
               
               
                 nCohort 2 
                 12 
                 nd 
                 8 
                 11 
                 nd 
                 9 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 1 
                 3.81 
                 nd 
                 4.59 
                 4.43 
                 nd 
                 4.43 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 1 
                 75% 
                 nd 
                 75% 
                 73% 
                 nd 
                 78% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 1 
                 75% 
                 nd 
                 83% 
                 82% 
                 nd 
                 82% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 2 
                 3.31 
                 nd 
                 3.81 
                 2.31 
                 nd 
                 2.31 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 2 
                 83% 
                 nd 
                 88% 
                 82% 
                 nd 
                 89% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 2 
                 68% 
                 nd 
                 74% 
                 46% 
                 nd 
                 44% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 3 
                 2.93 
                 nd 
                 3.31 
                 2.27 
                 nd 
                 1.51 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 3 
                 92% 
                 nd 
                 100%  
                 91% 
                 nd 
                 100%  
                 nd 
                 nd 
                 nd 
               
               
                 Spec 3 
                 60% 
                 nd 
                 67% 
                 44% 
                 nd 
                 18% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 4 
                 3.48 
                 nd 
                 3.58 
                 3.48 
                 nd 
                 3.58 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 4 
                 75% 
                 nd 
                 88% 
                 73% 
                 nd 
                 78% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 4 
                 70% 
                 nd 
                 70% 
                 70% 
                 nd 
                 70% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 5 
                 4.31 
                 nd 
                 4.35 
                 4.31 
                 nd 
                 4.35 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 5 
                 58% 
                 nd 
                 75% 
                 73% 
                 nd 
                 78% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 5 
                 80% 
                 nd 
                 80% 
                 80% 
                 nd 
                 80% 
                 nd 
                 nd 
                 nd 
               
               
                 Cutoff 6 
                 5.57 
                 nd 
                 5.57 
                 5.57 
                 nd 
                 5.57 
                 nd 
                 nd 
                 nd 
               
               
                 Sens 6 
                 42% 
                 nd 
                 50% 
                 55% 
                 nd 
                 56% 
                 nd 
                 nd 
                 nd 
               
               
                 Spec 6 
                 90% 
                 nd 
                 90% 
                 90% 
                 nd 
                 90% 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 2 
                 &gt;1.0 
                 nd 
                 &gt;0 
                 2.0 
                 nd 
                 1.0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 &lt;1.0 
                 nd 
                 &lt;na  
                 0.57 
                 nd 
                 1.0 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 &gt;0.062 
                 nd 
                 &gt;na  
                 0.18 
                 nd 
                 0.062 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart2 
                 na 
                 nd 
                 na 
                 22 
                 nd 
                 16 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 3 
                 &gt;3.0 
                 nd 
                 &gt;2.0 
                 0 
                 nd 
                 0 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 &lt;0.34 
                 nd 
                 &lt;0.56 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 &gt;0.31 
                 nd 
                 &gt;0.18 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart3 
                 na 
                 nd 
                 na 
                 na 
                 nd 
                 na 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart 4 
                 &gt;8.4 
                 nd 
                 &gt;6.3 
                 8.4 
                 nd 
                 7.3 
                 nd 
                 nd 
                 nd 
               
               
                 p Value 
                 &lt;0.046 
                 nd 
                 &lt;0.090 
                 0.047 
                 nd 
                 0.065 
                 nd 
                 nd 
                 nd 
               
               
                 95% CI of 
                 &gt;1.0 
                 nd 
                 &gt;0.75 
                 1.0 
                 nd 
                 0.89 
                 nd 
                 nd 
                 nd 
               
               
                 OR Quart4 
                 na 
                 nd 
                 na 
                 68 
                 nd 
                 60 
                 nd 
                 nd 
                 nd 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 Comparison of marker levels in enroll urine samples collected from Cohort 1 (patients 
               
               
                 that did not progress beyond RIFLE stage 0 or R within 48 hrs) and in enroll urine 
               
               
                 samples collected from Cohort 2 (subjects reaching RIFLE stage I or F within 48 hrs). 
               
               
                 Enroll samples from patients already at RIFLE stage I or F were included in Cohort 2. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 1.58 
                 0.320 
                 1.10 
                 0.745 
                 1.48 
                 0.289 
               
               
                 Average 
                 2.51 
                 1.59 
                 2.33 
                 2.38 
                 2.49 
                 1.43 
               
               
                 Stdev 
                 2.46 
                 2.27 
                 2.44 
                 2.80 
                 2.47 
                 2.15 
               
               
                 p(t-test) 
                   
                 0.046 
                   
                 0.95 
                   
                 0.034 
               
               
                 Min 
                 0.00152 
                 0.00133 
                 0.00152 
                 0.00133 
                 0.00152 
                 0.00212 
               
               
                 Max 
                 6.10 
                 6.07 
                 6.10 
                 5.80 
                 6.10 
                 6.07 
               
               
                 n (Samp) 
                 138 
                 35 
                 164 
                 8 
                 111 
                 30 
               
               
                 n (Patient) 
                 138 
                 35 
                 164 
                 8 
                 111 
                 30 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.37 
                 0.49 
                 0.35 
               
               
                   
                 SE 
                 0.055 
                 0.11 
                 0.060 
               
               
                   
                 p 
                 0.017 
                 0.93 
                 0.014 
               
               
                   
                 nCohort 1 
                 138 
                 164 
                 111 
               
               
                   
                 nCohort 2 
                 35 
                 8 
                 30 
               
               
                   
                 Cutoff 1 
                 0.0372 
                 0.255 
                 0.0372 
               
               
                   
                 Sens 1 
                 71% 
                 75% 
                 70% 
               
               
                   
                 Spec 1 
                 10% 
                 35% 
                 11% 
               
               
                   
                 Cutoff 2 
                 0.0182 
                 0.0627 
                 0.0182 
               
               
                   
                 Sens 2 
                 80% 
                 88% 
                 80% 
               
               
                   
                 Spec 2 
                  5% 
                 19% 
                  5% 
               
               
                   
                 Cutoff 3 
                 0.00270 
                 0 
                 0.00408 
               
               
                   
                 Sens 3 
                 91% 
                 100%  
                 90% 
               
               
                   
                 Spec 3 
                  1% 
                  0% 
                  3% 
               
               
                   
                 Cutoff 4 
                 5.08 
                 4.82 
                 5.08 
               
               
                   
                 Sens 4 
                 20% 
                 38% 
                 17% 
               
               
                   
                 Spec 4 
                 70% 
                 70% 
                 70% 
               
               
                   
                 Cutoff 5 
                 5.80 
                 5.80 
                 5.80 
               
               
                   
                 Sens 5 
                  3% 
                  0% 
                  3% 
               
               
                   
                 Spec 5 
                 95% 
                 95% 
                 95% 
               
               
                   
                 Cutoff 6 
                 5.80 
                 5.80 
                 5.80 
               
               
                   
                 Sens 6 
                  3% 
                  0% 
                  3% 
               
               
                   
                 Spec 6 
                 95% 
                 95% 
                 95% 
               
               
                   
                 OR Quart 2 
                 0.70 
                 0 
                 1.3 
               
               
                   
                 p Value 
                 0.56 
                 na 
                 0.71 
               
               
                   
                 95% CI of 
                 0.20 
                 na 
                 0.35 
               
               
                   
                 OR Quart2 
                 2.4 
                 na 
                 4.7 
               
               
                   
                 OR Quart 3 
                 1.6 
                 1.0 
                 1.8 
               
               
                   
                 p Value 
                 0.39 
                 1.0 
                 0.33 
               
               
                   
                 95% CI of 
                 0.55 
                 0.19 
                 0.54 
               
               
                   
                 OR Quart3 
                 4.7 
                 5.3 
                 6.3 
               
               
                   
                 OR Quart 4 
                 2.3 
                 0.65 
                 2.8 
               
               
                   
                 p Value 
                 0.12 
                 0.65 
                 0.084 
               
               
                   
                 95% CI of 
                 0.81 
                 0.10 
                 0.87 
               
               
                   
                 OR Quart4 
                 6.5 
                 4.1 
                 9.3 
               
               
                   
               
            
           
           
               
            
               
                 C-X-C motif chemokine 2 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.129 
                 5.17 
                 0.279 
                 17.3 
                 0.137 
                 4.46 
               
               
                 Average 
                 8.07 
                 22.1 
                 9.66 
                 35.0 
                 8.19 
                 23.9 
               
               
                 Stdev 
                 26.5 
                 45.2 
                 29.3 
                 59.8 
                 26.5 
                 47.2 
               
               
                 p(t-test) 
                   
                 0.0012 
                   
                 0.0052 
                   
                 0.0013 
               
               
                 Min 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
                 0.00804 
                 0.0260 
               
               
                 Max 
                 266 
                 217 
                 266 
                 217 
                 266 
                 217 
               
               
                 n (Samp) 
                 292 
                 61 
                 338 
                 12 
                 211 
                 55 
               
               
                 n (Patient) 
                 292 
                 61 
                 338 
                 12 
                 211 
                 55 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.66 
                 0.77 
                 0.66 
               
               
                   
                 SE 
                 0.041 
                 0.081 
                 0.044 
               
               
                   
                 p 
                 7.9E−5 
                 9.7E−4 
                 1.8E−4 
               
               
                   
                 nCohort 1 
                 292 
                 338 
                 211 
               
               
                   
                 nCohort 2 
                 61 
                 12 
                 55 
               
               
                   
                 Cutoff 1 
                 0.297 
                 6.27 
                 0.297 
               
               
                   
                 Sens 1 
                 70% 
                 75% 
                 71% 
               
               
                   
                 Spec 1 
                 54% 
                 75% 
                 54% 
               
               
                   
                 Cutoff 2 
                 0.00804 
                 5.62 
                 0.00804 
               
               
                   
                 Sens 2 
                 100%  
                 83% 
                 100%  
               
               
                   
                 Spec 2 
                  0% 
                 72% 
                  0% 
               
               
                   
                 Cutoff 3 
                 0.00804 
                 0.00804 
                 0.00804 
               
               
                   
                 Sens 3 
                 100%  
                 100%  
                 100%  
               
               
                   
                 Spec 3 
                  0% 
                  0% 
                  0% 
               
               
                   
                 Cutoff 4 
                 3.89 
                 4.33 
                 3.95 
               
               
                   
                 Sens 4 
                 52% 
                 83% 
                 51% 
               
               
                   
                 Spec 4 
                 70% 
                 70% 
                 70% 
               
               
                   
                 Cutoff 5 
                 6.98 
                 8.37 
                 7.79 
               
               
                   
                 Sens 5 
                 43% 
                 67% 
                 44% 
               
               
                   
                 Spec 5 
                 80% 
                 80% 
                 80% 
               
               
                   
                 Cutoff 6 
                 16.4 
                 20.5 
                 14.8 
               
               
                   
                 Sens 6 
                 30% 
                 50% 
                 36% 
               
               
                   
                 Spec 6 
                 90% 
                 90% 
                 90% 
               
               
                   
                 OR Quart 2 
                 0.16 
                 0 
                 0.17 
               
               
                   
                 p Value 
                 0.0046 
                 na 
                 0.0084 
               
               
                   
                 95% CI of 
                 0.044 
                 na 
                 0.047 
               
               
                   
                 OR Quart 2 
                 0.57 
                 na 
                 0.64 
               
               
                   
                 OR Quart 3 
                 0.85 
                 1.0 
                 1.0 
               
               
                   
                 p Value 
                 0.69 
                 1.0 
                 1.0 
               
               
                   
                 95% CI of 
                 0.39 
                 0.14 
                 0.43 
               
               
                   
                 OR Quart 3 
                 1.9 
                 7.3 
                 2.3 
               
               
                   
                 OR Quart 4 
                 2.1 
                 4.2 
                 2.1 
               
               
                   
                 p Value 
                 0.043 
                 0.073 
                 0.065 
               
               
                   
                 95% CI of 
                 1.0 
                 0.88 
                 0.96 
               
               
                   
                 OR Quart 4 
                 4.2 
                 21 
                 4.5 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 346 
                 1010 
                 nd 
                 nd 
                 344 
                 1250 
               
               
                 Average 
                 771 
                 2410 
                 nd 
                 nd 
                 800 
                 2590 
               
               
                 Stdev 
                 1050 
                 4300 
                 nd 
                 nd 
                 1090 
                 4450 
               
               
                 p(t-test) 
                   
                 5.2E−4 
                 nd 
                 nd 
                   
                 7.8E−4 
               
               
                 Min 
                 1.00E−9 
                 92.1 
                 nd 
                 nd 
                 1.00E−9 
                 92.1 
               
               
                 Max 
                 4830 
                 21100 
                 nd 
                 nd 
                 4830 
                 21100 
               
               
                 n (Samp) 
                 109 
                 24 
                 nd 
                 nd 
                 90 
                 22 
               
               
                 n (Patient) 
                 109 
                 24 
                 nd 
                 nd 
                 90 
                 22 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.70 
                 nd 
                 0.72 
               
               
                   
                 SE 
                 0.064 
                 nd 
                 0.066 
               
               
                   
                 p 
                 0.0018 
                 nd 
                 0.0012 
               
               
                   
                 nCohort 1 
                 109 
                 nd 
                 90 
               
               
                   
                 nCohort 2 
                 24 
                 nd 
                 22 
               
               
                   
                 Cutoff 1 
                 394 
                 nd 
                 394 
               
               
                   
                 Sens 1 
                 71% 
                 nd 
                 73% 
               
               
                   
                 Spec 1 
                 52% 
                 nd 
                 52% 
               
               
                   
                 Cutoff 2 
                 310 
                 nd 
                 346 
               
               
                   
                 Sens 2 
                 83% 
                 nd 
                 82% 
               
               
                   
                 Spec 2 
                 48% 
                 nd 
                 51% 
               
               
                   
                 Cutoff 3 
                 97.3 
                 nd 
                 114 
               
               
                   
                 Sens 3 
                 92% 
                 nd 
                 91% 
               
               
                   
                 Spec 3 
                 27% 
                 nd 
                 28% 
               
               
                   
                 Cutoff 4 
                 730 
                 nd 
                 730 
               
               
                   
                 Sens 4 
                 58% 
                 nd 
                 64% 
               
               
                   
                 Spec 4 
                 71% 
                 nd 
                 70% 
               
               
                   
                 Cutoff 5 
                 1440 
                 nd 
                 1440 
               
               
                   
                 Sens 5 
                 42% 
                 nd 
                 45% 
               
               
                   
                 Spec 5 
                 81% 
                 nd 
                 80% 
               
               
                   
                 Cutoff 6 
                 2150 
                 nd 
                 2150 
               
               
                   
                 Sens 6 
                 38% 
                 nd 
                 41% 
               
               
                   
                 Spec 6 
                 91% 
                 nd 
                 90% 
               
               
                   
                 OR Quart 2 
                 1.8 
                 nd 
                 1.8 
               
               
                   
                 p Value 
                 0.46 
                 nd 
                 0.45 
               
               
                   
                 95% CI of 
                 0.39 
                 nd 
                 0.39 
               
               
                   
                 OR Quart2 
                 8.2 
                 nd 
                 8.4 
               
               
                   
                 OR Quart 3 
                 2.2 
                 nd 
                 1.4 
               
               
                   
                 p Value 
                 0.29 
                 nd 
                 0.69 
               
               
                   
                 95% CI of 
                 0.51 
                 nd 
                 0.28 
               
               
                   
                 OR Quart3 
                 9.8 
                 nd 
                 6.9 
               
               
                   
                 OR Quart 4 
                 4.2 
                 nd 
                 4.6 
               
               
                   
                 p Value 
                 0.045 
                 nd 
                 0.035 
               
               
                   
                 95% CI of 
                 1.0 
                 nd 
                 1.1 
               
               
                   
                 OR Quart4 
                 17 
                 nd 
                 19 
               
               
                   
               
            
           
           
               
            
               
                 Cathepsin B 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.640 
                 1.39 
                 nd 
                 nd 
                 0.760 
                 1.39 
               
               
                 Average 
                 2.41 
                 7.35 
                 nd 
                 nd 
                 2.72 
                 6.90 
               
               
                 Stdev 
                 5.89 
                 14.4 
                 nd 
                 nd 
                 6.66 
                 14.6 
               
               
                 p(t-test) 
                   
                 0.0073 
                 nd 
                 nd 
                   
                 0.046 
               
               
                 Min 
                 1.00E−9 
                 1.00E−9 
                 nd 
                 nd 
                 1.00E−9 
                 1.00E−9 
               
               
                 Max 
                 51.8 
                 64.9 
                 nd 
                 nd 
                 51.8 
                 64.9 
               
               
                 n (Samp) 
                 110 
                 24 
                 nd 
                 nd 
                 91 
                 22 
               
               
                 n (Patient) 
                 110 
                 24 
                 nd 
                 nd 
                 91 
                 22 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.64 
                 nd 
                 0.63 
               
               
                   
                 SE 
                 0.066 
                 nd 
                 0.069 
               
               
                   
                 p 
                 0.029 
                 nd 
                 0.061 
               
               
                   
                 nCohort 1 
                 110 
                 nd 
                 91 
               
               
                   
                 nCohort 2 
                 24 
                 nd 
                 22 
               
               
                   
                 Cutoff 1 
                 0.604 
                 nd 
                 0.604 
               
               
                   
                 Sens 1 
                 71% 
                 nd 
                 73% 
               
               
                   
                 Spec 1 
                 50% 
                 nd 
                 47% 
               
               
                   
                 Cutoff 2 
                 0.388 
                 nd 
                 0.460 
               
               
                   
                 Sens 2 
                 83% 
                 nd 
                 82% 
               
               
                   
                 Spec 2 
                 37% 
                 nd 
                 37% 
               
               
                   
                 Cutoff 3 
                 0.148 
                 nd 
                 0.148 
               
               
                   
                 Sens 3 
                 92% 
                 nd 
                 91% 
               
               
                   
                 Spec 3 
                 18% 
                 nd 
                 18% 
               
               
                   
                 Cutoff 4 
                 1.29 
                 nd 
                 1.29 
               
               
                   
                 Sens 4 
                 54% 
                 nd 
                 55% 
               
               
                   
                 Spec 4 
                 70% 
                 nd 
                 70% 
               
               
                   
                 Cutoff 5 
                 2.34 
                 nd 
                 2.34 
               
               
                   
                 Sens 5 
                 42% 
                 nd 
                 41% 
               
               
                   
                 Spec 5 
                 80% 
                 nd 
                 80% 
               
               
                   
                 Cutoff 6 
                 5.45 
                 nd 
                 7.18 
               
               
                   
                 Sens 6 
                 25% 
                 nd 
                 23% 
               
               
                   
                 Spec 6 
                 90% 
                 nd 
                 90% 
               
               
                   
                 OR Quart 2 
                 1.2 
                 nd 
                 1.0 
               
               
                   
                 p Value 
                 0.76 
                 nd 
                 1.0 
               
               
                   
                 95% CI of 
                 0.30 
                 nd 
                 0.22 
               
               
                   
                 OR Quart2 
                 5.1 
                 nd 
                 4.5 
               
               
                   
                 OR Quart 3 
                 1.3 
                 nd 
                 1.3 
               
               
                   
                 p Value 
                 0.72 
                 nd 
                 0.72 
               
               
                   
                 95% CI of 
                 0.31 
                 nd 
                 0.31 
               
               
                   
                 OR Quart3 
                 5.3 
                 nd 
                 5.5 
               
               
                   
                 OR Quart 4 
                 3.0 
                 nd 
                 2.7 
               
               
                   
                 p Value 
                 0.090 
                 nd 
                 0.14 
               
               
                   
                 95% CI of 
                 0.84 
                 nd 
                 0.72 
               
               
                   
                 OR Quart4 
                 11 
                 nd 
                 10 
               
               
                   
               
            
           
           
               
            
               
                 Neprilysin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 1.28 
                 1.52 
                 nd 
                 nd 
                 1.28 
                 1.32 
               
               
                 Average 
                 6.20 
                 17.1 
                 nd 
                 nd 
                 5.94 
                 19.1 
               
               
                 Stdev 
                 16.9 
                 25.3 
                 nd 
                 nd 
                 17.0 
                 26.3 
               
               
                 p(t-test) 
                   
                 0.11 
                 nd 
                 nd 
                   
                 0.074 
               
               
                 Min 
                 0.0869 
                 0.0203 
                 nd 
                 nd 
                 0.0869 
                 0.0203 
               
               
                 Max 
                 98.9 
                 64.3 
                 nd 
                 nd 
                 98.9 
                 64.3 
               
               
                 n (Samp) 
                 50 
                 9 
                 nd 
                 nd 
                 42 
                 8 
               
               
                 n (Patient) 
                 50 
                 9 
                 nd 
                 nd 
                 42 
                 8 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.57 
                 nd 
                 0.57 
               
               
                   
                 SE 
                 0.11 
                 nd 
                 0.11 
               
               
                   
                 p 
                 0.51 
                 nd 
                 0.53 
               
               
                   
                 nCohort 1 
                 50 
                 nd 
                 42 
               
               
                   
                 nCohort 2 
                 9 
                 nd 
                 8 
               
               
                   
                 Cutoff 1 
                 0.820 
                 nd 
                 0.820 
               
               
                   
                 Sens 1 
                 78% 
                 nd 
                 75% 
               
               
                   
                 Spec 1 
                 40% 
                 nd 
                 43% 
               
               
                   
                 Cutoff 2 
                 0.238 
                 nd 
                 0.238 
               
               
                   
                 Sens 2 
                 89% 
                 nd 
                 88% 
               
               
                   
                 Spec 2 
                 10% 
                 nd 
                 10% 
               
               
                   
                 Cutoff 3 
                 0 
                 nd 
                 0 
               
               
                   
                 Sens 3 
                 100%  
                 nd 
                 100%  
               
               
                   
                 Spec 3 
                  0% 
                 nd 
                  0% 
               
               
                   
                 Cutoff 4 
                 1.68 
                 nd 
                 1.68 
               
               
                   
                 Sens 4 
                 33% 
                 nd 
                 38% 
               
               
                   
                 Spec 4 
                 70% 
                 nd 
                 71% 
               
               
                   
                 Cutoff 5 
                 3.30 
                 nd 
                 3.50 
               
               
                   
                 Sens 5 
                 33% 
                 nd 
                 38% 
               
               
                   
                 Spec 5 
                 80% 
                 nd 
                 81% 
               
               
                   
                 Cutoff 6 
                 10.8 
                 nd 
                 10.8 
               
               
                   
                 Sens 6 
                 33% 
                 nd 
                 38% 
               
               
                   
                 Spec 6 
                 90% 
                 nd 
                 90% 
               
               
                   
                 OR Quart 2 
                 0.92 
                 nd 
                 0.91 
               
               
                   
                 p Value 
                 0.94 
                 nd 
                 0.93 
               
               
                   
                 95% CI of 
                 0.11 
                 nd 
                 0.11 
               
               
                   
                 OR Quart2 
                 7.6 
                 nd 
                 7.7 
               
               
                   
                 OR Quart 3 
                 0.92 
                 nd 
                 0.45 
               
               
                   
                 p Value 
                 0.94 
                 nd 
                 0.54 
               
               
                   
                 95% CI of 
                 0.11 
                 nd 
                 0.036 
               
               
                   
                 OR Quart3 
                 7.6 
                 nd 
                 5.8 
               
               
                   
                 OR Quart 4 
                 1.5 
                 nd 
                 1.5 
               
               
                   
                 p Value 
                 0.69 
                 nd 
                 0.69 
               
               
                   
                 95% CI of 
                 0.21 
                 nd 
                 0.20 
               
               
                   
                 OR Quart4 
                 11 
                 nd 
                 11 
               
               
                   
               
            
           
           
               
            
               
                 Carbonic anhydrase IX 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.0111 
                 0.0219 
                 nd 
                 nd 
                 0.0113 
                 0.0232 
               
               
                 Average 
                 0.0193 
                 0.114 
                 nd 
                 nd 
                 0.0192 
                 0.126 
               
               
                 Stdev 
                 0.0252 
                 0.280 
                 nd 
                 nd 
                 0.0259 
                 0.297 
               
               
                 p(t-test) 
                   
                 0.018 
                 nd 
                 nd 
                   
                 0.021 
               
               
                 Min 
                 0.000386 
                 0.00345 
                 nd 
                 nd 
                 0.00102 
                 0.00345 
               
               
                 Max 
                 0.119 
                 0.859 
                 nd 
                 nd 
                 0.119 
                 0.859 
               
               
                 n (Samp) 
                 50 
                 9 
                 nd 
                 nd 
                 42 
                 8 
               
               
                 n (Patient) 
                 50 
                 9 
                 nd 
                 nd 
                 42 
                 8 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.70 
                 nd 
                 0.71 
               
               
                   
                 SE 
                 0.10 
                 nd 
                 0.11 
               
               
                   
                 p 
                 0.054 
                 nd 
                 0.058 
               
               
                   
                 nCohort 1 
                 50 
                 nd 
                 42 
               
               
                   
                 nCohort 2 
                 9 
                 nd 
                 8 
               
               
                   
                 Cutoff 1 
                 0.0179 
                 nd 
                 0.0179 
               
               
                   
                 Sens 1 
                 78% 
                 nd 
                 75% 
               
               
                   
                 Spec 1 
                 68% 
                 nd 
                 69% 
               
               
                   
                 Cutoff 2 
                 0.0121 
                 nd 
                 0.0121 
               
               
                   
                 Sens 2 
                 89% 
                 nd 
                 88% 
               
               
                   
                 Spec 2 
                 58% 
                 nd 
                 57% 
               
               
                   
                 Cutoff 3 
                 0.00296 
                 nd 
                 0.00296 
               
               
                   
                 Sens 3 
                 100%  
                 nd 
                 100%  
               
               
                   
                 Spec 3 
                 26% 
                 nd 
                 24% 
               
               
                   
                 Cutoff 4 
                 0.0205 
                 nd 
                 0.0205 
               
               
                   
                 Sens 4 
                 56% 
                 nd 
                 50% 
               
               
                   
                 Spec 4 
                 70% 
                 nd 
                 71% 
               
               
                   
                 Cutoff 5 
                 0.0284 
                 nd 
                 0.0274 
               
               
                   
                 Sens 5 
                 22% 
                 nd 
                 38% 
               
               
                   
                 Spec 5 
                 80% 
                 nd 
                 81% 
               
               
                   
                 Cutoff 6 
                 0.0421 
                 nd 
                 0.0358 
               
               
                   
                 Sens 6 
                 11% 
                 nd 
                 12% 
               
               
                   
                 Spec 6 
                 90% 
                 nd 
                 90% 
               
               
                   
                 OR Quart 2 
                 0 
                 nd 
                 0 
               
               
                   
                 p Value 
                 na 
                 nd 
                 na 
               
               
                   
                 95% CI of 
                 na 
                 nd 
                 na 
               
               
                   
                 OR Quart2 
                 na 
                 nd 
                 na 
               
               
                   
                 OR Quart 3 
                 6.5 
                 nd 
                 3.7 
               
               
                   
                 p Value 
                 0.11 
                 nd 
                 0.29 
               
               
                   
                 95% CI of 
                 0.65 
                 nd 
                 0.32 
               
               
                   
                 OR Quart3 
                 65 
                 nd 
                 42 
               
               
                   
                 OR Quart 4 
                 3.2 
                 nd 
                 4.9 
               
               
                   
                 p Value 
                 0.33 
                 nd 
                 0.19 
               
               
                   
                 95% CI of 
                 0.30 
                 nd 
                 0.46 
               
               
                   
                 OR Quart4 
                 36 
                 nd 
                 52 
               
               
                   
               
            
           
           
               
            
               
                 Dipeptidyl peptidase IV 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 130 
                 793 
                 nd 
                 nd 
                 129 
                 1050 
               
               
                 Average 
                 513 
                 1820 
                 nd 
                 nd 
                 486 
                 2010 
               
               
                 Stdev 
                 904 
                 3030 
                 nd 
                 nd 
                 840 
                 3170 
               
               
                 p(t-test) 
                   
                 8.5E−4 
                 nd 
                 nd 
                   
                 4.7E−4 
               
               
                 Min 
                 0.924 
                 0.651 
                 nd 
                 nd 
                 0.924 
                 10.1 
               
               
                 Max 
                 5010 
                 12500 
                 nd 
                 nd 
                 5010 
                 12500 
               
               
                 n (Samp) 
                 89 
                 18 
                 nd 
                 nd 
                 74 
                 16 
               
               
                 n (Patient) 
                 89 
                 18 
                 nd 
                 nd 
                 74 
                 16 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.67 
                 nd 
                 0.71 
               
               
                   
                 SE 
                 0.075 
                 nd 
                 0.078 
               
               
                   
                 p 
                 0.027 
                 nd 
                 0.0079 
               
               
                   
                 nCohort 1 
                 89 
                 nd 
                 74 
               
               
                   
                 nCohort 2 
                 18 
                 nd 
                 16 
               
               
                   
                 Cutoff 1 
                 173 
                 nd 
                 161 
               
               
                   
                 Sens 1 
                 72% 
                 nd 
                 75% 
               
               
                   
                 Spec 1 
                 56% 
                 nd 
                 57% 
               
               
                   
                 Cutoff 2 
                 18.2 
                 nd 
                 48.0 
               
               
                   
                 Sens 2 
                 83% 
                 nd 
                 81% 
               
               
                   
                 Spec 2 
                 22% 
                 nd 
                 35% 
               
               
                   
                 Cutoff 3 
                 8.88 
                 nd 
                 15.1 
               
               
                   
                 Sens 3 
                 94% 
                 nd 
                 94% 
               
               
                   
                 Spec 3 
                 12% 
                 nd 
                 22% 
               
               
                   
                 Cutoff 4 
                 457 
                 nd 
                 457 
               
               
                   
                 Sens 4 
                 61% 
                 nd 
                 62% 
               
               
                   
                 Spec 4 
                 71% 
                 nd 
                 70% 
               
               
                   
                 Cutoff 5 
                 837 
                 nd 
                 698 
               
               
                   
                 Sens 5 
                 50% 
                 nd 
                 56% 
               
               
                   
                 Spec 5 
                 81% 
                 nd 
                 81% 
               
               
                   
                 Cutoff 6 
                 1810 
                 nd 
                 1810 
               
               
                   
                 Sens 6 
                 28% 
                 nd 
                 31% 
               
               
                   
                 Spec 6 
                 91% 
                 nd 
                 91% 
               
               
                   
                 OR Quart 2 
                 0.21 
                 nd 
                 0.29 
               
               
                   
                 p Value 
                 0.18 
                 nd 
                 0.30 
               
               
                   
                 95% CI of 
                 0.022 
                 nd 
                 0.028 
               
               
                   
                 OR Quart2 
                 2.0 
                 nd 
                 3.0 
               
               
                   
                 OR Quart 3 
                 0.96 
                 nd 
                 1.0 
               
               
                   
                 p Value 
                 0.95 
                 nd 
                 1.0 
               
               
                   
                 95% CI of 
                 0.21 
                 nd 
                 0.18 
               
               
                   
                 OR Quart3 
                 4.3 
                 nd 
                 5.6 
               
               
                   
                 OR Quart 4 
                 2.8 
                 nd 
                 4.1 
               
               
                   
                 p Value 
                 0.14 
                 nd 
                 0.063 
               
               
                   
                 95% CI of 
                 0.73 
                 nd 
                 0.93 
               
               
                   
                 OR Quart4 
                 10 
                 nd 
                 18 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 Comparison of marker levels in enroll EDTA samples collected from Cohort 1 (patients 
               
               
                 that did not progress beyond RIFLE stage 0 or R within 48 hrs) and in enroll EDTA 
               
               
                 samples collected from Cohort 2 (subjects reaching RIFLE stage I or F within 48 hrs). 
               
               
                 Enroll samples from patients already at stage I or F were included in Cohort 2. 
               
               
                   
               
             
            
               
                 Beta-2-microglobulin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 2.23 
                 3.61 
                 2.34 
                 4.39 
                 2.30 
                 3.64 
               
               
                 Average 
                 3.01 
                 4.59 
                 3.14 
                 6.99 
                 2.96 
                 4.13 
               
               
                 Stdev 
                 2.15 
                 4.09 
                 2.26 
                 6.39 
                 2.14 
                 2.79 
               
               
                 p(t-test) 
                   
                 0.0018 
                   
                 2.7E−5 
                   
                 0.014 
               
               
                 Min 
                 0.824 
                 1.38 
                 0.824 
                 2.19 
                 0.824 
                 1.38 
               
               
                 Max 
                 13.8 
                 22.7 
                 13.8 
                 22.7 
                 13.8 
                 11.3 
               
               
                 n (Samp) 
                 139 
                 36 
                 165 
                 9 
                 110 
                 31 
               
               
                 n (Patient) 
                 139 
                 36 
                 165 
                 9 
                 110 
                 31 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.64 
                 0.79 
                 0.64 
               
               
                   
                 SE 
                 0.054 
                 0.092 
                 0.059 
               
               
                   
                 p 
                 0.0077 
                 0.0017 
                 0.020 
               
               
                   
                 nCohort 1 
                 139 
                 165 
                 110 
               
               
                   
                 nCohort 2 
                 36 
                 9 
                 31 
               
               
                   
                 Cutoff 1 
                 2.19 
                 3.52 
                 2.19 
               
               
                   
                 Sens 1 
                 72% 
                 78% 
                 71% 
               
               
                   
                 Spec 1 
                 49% 
                 71% 
                 47% 
               
               
                   
                 Cutoff 2 
                 1.81 
                 2.23 
                 1.76 
               
               
                   
                 Sens 2 
                 81% 
                 89% 
                 81% 
               
               
                   
                 Spec 2 
                 31% 
                 48% 
                 28% 
               
               
                   
                 Cutoff 3 
                 1.51 
                 2.18 
                 1.50 
               
               
                   
                 Sens 3 
                 94% 
                 100%  
                 94% 
               
               
                   
                 Spec 3 
                 21% 
                 46% 
                 22% 
               
               
                   
                 Cutoff 4 
                 3.15 
                 3.48 
                 3.00 
               
               
                   
                 Sens 4 
                 53% 
                 78% 
                 55% 
               
               
                   
                 Spec 4 
                 71% 
                 70% 
                 70% 
               
               
                   
                 Cutoff 5 
                 4.30 
                 4.41 
                 4.15 
               
               
                   
                 Sens 5 
                 36% 
                 44% 
                 39% 
               
               
                   
                 Spec 5 
                 81% 
                 80% 
                 80% 
               
               
                   
                 Cutoff 6 
                 5.95 
                 6.04 
                 5.49 
               
               
                   
                 Sens 6 
                 22% 
                 44% 
                 26% 
               
               
                   
                 Spec 6 
                 91% 
                 91% 
                 90% 
               
               
                   
                 OR Quart 2 
                 1.2 
                 &gt;2.0 
                 0.81 
               
               
                   
                 p Value 
                 0.80 
                 &lt;0.56 
                 0.74 
               
               
                   
                 95% CI of 
                 0.36 
                 &gt;0.18 
                 0.22 
               
               
                   
                 OR Quart2 
                 3.8 
                 na 
                 2.9 
               
               
                   
                 OR Quart 3 
                 1.6 
                 &gt;1.0 
                 1.2 
               
               
                   
                 p Value 
                 0.42 
                 &lt;0.99 
                 0.76 
               
               
                   
                 95% CI of 
                 0.51 
                 &gt;0.062 
                 0.36 
               
               
                   
                 OR Quart3 
                 4.9 
                 na 
                 4.0 
               
               
                   
                 OR Quart 4 
                 2.9 
                 &gt;6.8 
                 2.7 
               
               
                   
                 p Value 
                 0.053 
                 &lt;0.082 
                 0.076 
               
               
                   
                 95% CI of 
                 0.99 
                 &gt;0.78 
                 0.90 
               
               
                   
                 OR Quart4 
                 8.4 
                 na 
                 8.3 
               
               
                   
               
            
           
           
               
            
               
                 Renin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 3930 
                 3630 
                 nd 
                 nd 
                 4300 
                 3630 
               
               
                 Average 
                 4190 
                 5880 
                 nd 
                 nd 
                 4310 
                 5880 
               
               
                 Stdev 
                 1810 
                 6690 
                 nd 
                 nd 
                 1930 
                 6690 
               
               
                 p(t-test) 
                   
                 0.15 
                 nd 
                 nd 
                   
                 0.22 
               
               
                 Min 
                 1840 
                 2100 
                 nd 
                 nd 
                 1840 
                 2100 
               
               
                 Max 
                 10400 
                 23300 
                 nd 
                 nd 
                 10400 
                 23300 
               
               
                 n (Samp) 
                 43 
                 9 
                 nd 
                 nd 
                 36 
                 9 
               
               
                 n (Patient) 
                 43 
                 9 
                 nd 
                 nd 
                 36 
                 9 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.50 
                 nd 
                 0.48 
               
               
                   
                 SE 
                 0.11 
                 nd 
                 0.11 
               
               
                   
                 p 
                 0.99 
                 nd 
                 0.89 
               
               
                   
                 nCohort 1 
                 43 
                 nd 
                 36 
               
               
                   
                 nCohort 2 
                 9 
                 nd 
                 9 
               
               
                   
                 Cutoff 1 
                 2560 
                 nd 
                 2560 
               
               
                   
                 Sens 1 
                 78% 
                 nd 
                 78% 
               
               
                   
                 Spec 1 
                 23% 
                 nd 
                 25% 
               
               
                   
                 Cutoff 2 
                 2110 
                 nd 
                 2110 
               
               
                   
                 Sens 2 
                 89% 
                 nd 
                 89% 
               
               
                   
                 Spec 2 
                  9% 
                 nd 
                 11% 
               
               
                   
                 Cutoff 3 
                 2100 
                 nd 
                 2100 
               
               
                   
                 Sens 3 
                 100%  
                 nd 
                 100%  
               
               
                   
                 Spec 3 
                  7% 
                 nd 
                  8% 
               
               
                   
                 Cutoff 4 
                 4690 
                 nd 
                 4900 
               
               
                   
                 Sens 4 
                 22% 
                 nd 
                 22% 
               
               
                   
                 Spec 4 
                 72% 
                 nd 
                 72% 
               
               
                   
                 Cutoff 5 
                 5340 
                 nd 
                 5550 
               
               
                   
                 Sens 5 
                 22% 
                 nd 
                 22% 
               
               
                   
                 Spec 5 
                 81% 
                 nd 
                 81% 
               
               
                   
                 Cutoff 6 
                 6480 
                 nd 
                 6490 
               
               
                   
                 Sens 6 
                 11% 
                 nd 
                 11% 
               
               
                   
                 Spec 6 
                 91% 
                 nd 
                 92% 
               
               
                   
                 OR Quart 2 
                 1.0 
                 nd 
                 1.1 
               
               
                   
                 p Value 
                 1.0 
                 nd 
                 0.92 
               
               
                   
                 95% CI of 
                 0.12 
                 nd 
                 0.13 
               
               
                   
                 OR Quart2 
                 8.4 
                 nd 
                 9.6 
               
               
                   
                 OR Quart 3 
                 1.0 
                 nd 
                 1.9 
               
               
                   
                 p Value 
                 1.0 
                 nd 
                 0.54 
               
               
                   
                 95% CI of 
                 0.12 
                 nd 
                 0.25 
               
               
                   
                 OR Quart3 
                 8.4 
                 nd 
                 14 
               
               
                   
                 OR Quart 4 
                 1.6 
                 nd 
                 1.1 
               
               
                   
                 p Value 
                 0.62 
                 nd 
                 0.92 
               
               
                   
                 95% CI of 
                 0.23 
                 nd 
                 0.13 
               
               
                   
                 OR Quart4 
                 12 
                 nd 
                 9.6 
               
               
                   
               
            
           
           
               
            
               
                 Neprilysin 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.607 
                 0.869 
                 nd 
                 nd 
                 0.605 
                 0.869 
               
               
                 Average 
                 0.878 
                 1.43 
                 nd 
                 nd 
                 0.862 
                 1.43 
               
               
                 Stdev 
                 0.838 
                 1.32 
                 nd 
                 nd 
                 0.864 
                 1.32 
               
               
                 p(t-test) 
                   
                 0.12 
                 nd 
                 nd 
                   
                 0.12 
               
               
                 Min 
                 0.0682 
                 0.312 
                 nd 
                 nd 
                 0.0682 
                 0.312 
               
               
                 Max 
                 3.76 
                 4.43 
                 nd 
                 nd 
                 3.76 
                 4.43 
               
               
                 n (Samp) 
                 42 
                 9 
                 nd 
                 nd 
                 36 
                 9 
               
               
                 n (Patient) 
                 42 
                 9 
                 nd 
                 nd 
                 36 
                 9 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.66 
                 nd 
                 0.68 
               
               
                   
                 SE 
                 0.11 
                 nd 
                 0.11 
               
               
                   
                 p 
                 0.14 
                 nd 
                 0.095 
               
               
                   
                 nCohort 1 
                 42 
                 nd 
                 36 
               
               
                   
                 nCohort 2 
                 9 
                 nd 
                 9 
               
               
                   
                 Cutoff 1 
                 0.685 
                 nd 
                 0.684 
               
               
                   
                 Sens 1 
                 78% 
                 nd 
                 78% 
               
               
                   
                 Spec 1 
                 69% 
                 nd 
                 72% 
               
               
                   
                 Cutoff 2 
                 0.337 
                 nd 
                 0.337 
               
               
                   
                 Sens 2 
                 89% 
                 nd 
                 89% 
               
               
                   
                 Spec 2 
                 10% 
                 nd 
                  8% 
               
               
                   
                 Cutoff 3 
                 0.308 
                 nd 
                 0.308 
               
               
                   
                 Sens 3 
                 100%  
                 nd 
                 100%  
               
               
                   
                 Spec 3 
                  5% 
                 nd 
                  6% 
               
               
                   
                 Cutoff 4 
                 0.806 
                 nd 
                 0.684 
               
               
                   
                 Sens 4 
                 67% 
                 nd 
                 78% 
               
               
                   
                 Spec 4 
                 71% 
                 nd 
                 72% 
               
               
                   
                 Cutoff 5 
                 0.992 
                 nd 
                 0.821 
               
               
                   
                 Sens 5 
                 33% 
                 nd 
                 67% 
               
               
                   
                 Spec 5 
                 81% 
                 nd 
                 81% 
               
               
                   
                 Cutoff 6 
                 1.84 
                 nd 
                 1.84 
               
               
                   
                 Sens 6 
                 33% 
                 nd 
                 33% 
               
               
                   
                 Spec 6 
                 90% 
                 nd 
                 92% 
               
               
                   
                 OR Quart 2 
                 0 
                 nd 
                 0 
               
               
                   
                 p Value 
                 na 
                 nd 
                 na 
               
               
                   
                 95% CI of 
                 na 
                 nd 
                 na 
               
               
                   
                 OR Quart2 
                 na 
                 nd 
                 na 
               
               
                   
                 OR Quart 3 
                 2.2 
                 nd 
                 1.0 
               
               
                   
                 p Value 
                 0.42 
                 nd 
                 1.0 
               
               
                   
                 95% CI of 
                 0.33 
                 nd 
                 0.11 
               
               
                   
                 OR Quart3 
                 15 
                 nd 
                 8.7 
               
               
                   
                 OR Quart 4 
                 1.5 
                 nd 
                 3.2 
               
               
                   
                 p Value 
                 0.69 
                 nd 
                 0.23 
               
               
                   
                 95% CI of 
                 0.20 
                 nd 
                 0.47 
               
               
                   
                 OR Quart4 
                 11 
                 nd 
                 22 
               
               
                   
               
            
           
           
               
            
               
                 Carbonic anhydrase IX 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
                 Cohort 1 
                 Cohort 2 
               
               
                   
               
               
                 Median 
                 0.116 
                 0.113 
                 nd 
                 nd 
                 0.122 
                 0.113 
               
               
                 Average 
                 0.145 
                 0.340 
                 nd 
                 nd 
                 0.150 
                 0.340 
               
               
                 Stdev 
                 0.132 
                 0.598 
                 nd 
                 nd 
                 0.138 
                 0.598 
               
               
                 p(t-test) 
                   
                 0.053 
                 nd 
                 nd 
                   
                 0.083 
               
               
                 Min 
                 0.0202 
                 0.0472 
                 nd 
                 nd 
                 0.0202 
                 0.0472 
               
               
                 Max 
                 0.657 
                 1.90 
                 nd 
                 nd 
                 0.657 
                 1.90 
               
               
                 n (Samp) 
                 43 
                 9 
                 nd 
                 nd 
                 36 
                 9 
               
               
                 n (Patient) 
                 43 
                 9 
                 nd 
                 nd 
                 36 
                 9 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 At Enrollment 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 sCr or UO 
                 sCr only 
                 UO only 
               
               
                   
               
               
                   
                 AUC 
                 0.51 
                 nd 
                 0.49 
               
               
                   
                 SE 
                 0.11 
                 nd 
                 0.11 
               
               
                   
                 p 
                 0.95 
                 nd 
                 0.95 
               
               
                   
                 nCohort 1 
                 43 
                 nd 
                 36 
               
               
                   
                 nCohort 2 
                 9 
                 nd 
                 9 
               
               
                   
                 Cutoff 1 
                 0.0653 
                 nd 
                 0.0579 
               
               
                   
                 Sens 1 
                 78% 
                 nd 
                 78% 
               
               
                   
                 Spec 1 
                 21% 
                 nd 
                 19% 
               
               
                   
                 Cutoff 2 
                 0.0472 
                 nd 
                 0.0472 
               
               
                   
                 Sens 2 
                 89% 
                 nd 
                 89% 
               
               
                   
                 Spec 2 
                 14% 
                 nd 
                 14% 
               
               
                   
                 Cutoff 3 
                 0.0467 
                 nd 
                 0.0467 
               
               
                   
                 Sens 3 
                 100%  
                 nd 
                 100%  
               
               
                   
                 Spec 3 
                 14% 
                 nd 
                 14% 
               
               
                   
                 Cutoff 4 
                 0.147 
                 nd 
                 0.155 
               
               
                   
                 Sens 4 
                 33% 
                 nd 
                 33% 
               
               
                   
                 Spec 4 
                 72% 
                 nd 
                 72% 
               
               
                   
                 Cutoff 5 
                 0.183 
                 nd 
                 0.183 
               
               
                   
                 Sens 5 
                 33% 
                 nd 
                 33% 
               
               
                   
                 Spec 5 
                 81% 
                 nd 
                 81% 
               
               
                   
                 Cutoff 6 
                 0.241 
                 nd 
                 0.241 
               
               
                   
                 Sens 6 
                 33% 
                 nd 
                 33% 
               
               
                   
                 Spec 6 
                 91% 
                 nd 
                 92% 
               
               
                   
                 OR Quart 2 
                 0.61 
                 nd 
                 0.30 
               
               
                   
                 p Value 
                 0.62 
                 nd 
                 0.33 
               
               
                   
                 95% CI of 
                 0.083 
                 nd 
                 0.026 
               
               
                   
                 OR Quart2 
                 4.4 
                 nd 
                 3.4 
               
               
                   
                 OR Quart 3 
                 0.28 
                 nd 
                 0.67 
               
               
                   
                 p Value 
                 0.30 
                 nd 
                 0.69 
               
               
                   
                 95% CI of 
                 0.025 
                 nd 
                 0.089 
               
               
                   
                 OR Quart3 
                 3.1 
                 nd 
                 5.0 
               
               
                   
                 OR Quart 4 
                 1.0 
                 nd 
                 1.1 
               
               
                   
                 p Value 
                 1.0 
                 nd 
                 0.90 
               
               
                   
                 95% CI of 
                 0.16 
                 nd 
                 0.17 
               
               
                   
                 OR Quart4 
                 6.2 
                 nd 
                 7.2 
               
               
                   
               
            
           
         
       
     
     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.