Observational Study of Pediatric Acute Kidney Injury, Risk Factors and Outcomes
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury
Study type: Observational [Patient Registry]

Summary: 
      Pediatric acute kidney injury (AKI) is associated with increased morbidity and mortality in
      critically ill patients. Currently, understanding of the epidemiology and diagnosis of AKI in
      children is limited by single center retrospective data and inconsistent diagnostic and
      stratification criteria. The hypotheses of the AWARE study is that 1) renal angina, a
      composite of early injury signs and risk of disease, will predict severe subsequent AKI in
      critically ill children and 2) the incorporation of urinary biomarkers into the renal angina
      scoring system will improve the prediction of the severe injury. The AWARE study is conducted
      to describe AKI epidemiology in a heterogeneous multinational cohort of critically ill
      children, characterize AKI risk factors and associated morbidity, and validate the KDIGO AKI
      criteria as a predictor of pediatric AKI outcomes. The multi-center, multi-national registry
      will create the largest ever repository of information available on AKI in children.
    

Detailed description: 
      The AWARE study is a multicenter prospective observational study designed to achieve the
      following three goals:

        1. Establish the first international pediatric AKI registry to describe in detail the
           epidemiology and outcome of AKI in different pediatric and cardiac ICUs around the
           world.

        2. Validate the precision of RAI in ruling out AKI in a large, heterogeneous study
           population.

        3. Evaluate the predictive value of using RAI before and after the incorporation of four
           different urinary AKI biomarkers used in different combinations.

      To achieve these primary goals, children admitted to PICUs and/or pediatric cardiac ICUs from
      different US and international centers will be screened for enrollment eligibility. Patients
      admitted to general PICU and non-surgical patients admitted to cardiac ICUs are considered
      the target population of AWARE. Patients admitted to neonatal ICUs and post-surgical
      admissions to cardiac ICUs are not included in AWARE. Both clinical variables and urinary
      biomarkers would be needed to accomplish the analysis.

      A- Clinical variables: Clinical data of interest at study entry will include age, gender,
      race, ethnicity, height, weight, date of ICU admission, date of ICU discharge, date of
      hospital discharge, admission diagnosis(es) and primary co-morbidities. Creatinine clearance
      (eCrCl) will be estimated by the modified Schwartz formula29. Baseline creatinine will be
      collected if the patient had a listed value in the medical record in the 90 days prior to
      admission, with the lowest value selected if multiple measurements are present. In cases
      where no baseline data is available, reference eCrCl will be estimated as 120 mL/min/1.73m2.
      30

      Clinical data will be recorded on admission and on a daily basis for the first seven days of
      the PICU admission or till discharge from the PICU whatever is earlier. Another set of data
      will be collected to evaluate the primary and secondary outcomes of the study (see later).
      The outcomes data will be collected on day 28 after ICU admission when available or by most
      recent available data before hospital discharge for patients with no available data on day
      28.

      Clinical parameters of interest include:

        -  use of fluid resuscitation in peri-ICU period ( normal saline, PlasmalyteTM ,Ringer's
           Lactate, 5% Albumin, starch based fluids including dextran composites)

        -  daily first shift heart rate (beats per minute) from day 1 through day 7 (at the most)
           of ICU admission

        -  daily first shift respiratory rate (breaths per minute) from day 1 through day 7 (at the
           most) of ICU admission

        -  daily first shift systolic and diastolic blood pressure and mean arterial pressure
           (arterial line measurements will be used when available) from day 1 through day 7 (at
           the most) of ICU admission

        -  daily first shift temperature from day 1 through day 7 (at the most) of ICU admission

        -  use of mechanical ventilation (yes/no)

        -  daily first shift mean airway pressure when applicable from day 1 through day 7 (at the
           most) of ICU admission

        -  duration of mechanical ventilation

        -  daily first shift oxygen blood saturation ( SpO2) from day 1 through day 7 (at the most)
           of ICU admission

        -  daily first shift fraction of inspired oxygen (FiO2) (%) from day 1 through day 7 (at
           the most) of ICU admission

        -  use of nephrotoxins (yes/no) from day 0 through day 7 (at the most) of ICU admission

        -  types of nephrotoxic agents:

             -  Nonsteroidal anti-inflammatory drugs (NSAIDS)

             -  Aminoglycosides,

             -  anti-viral therapy,

             -  Vancomycin,

             -  Piperacillin/Tazobactam,

             -  Calcineurin inhibitors,

             -  IV radio-contrasts ( Including Gadolinium for MRI)

        -  use of vasoactive support (yes/no) from day 0 through day 7 (at the most) of ICU
           admission

        -  use of diuretics on day 0 and during admission (yes/no)

        -  class of diuretics used (Loop diuretics, Thiazides, Potassium sparing, Carbonic
           anhydrase inhibitors, Vasopressin antagonist, Osmotic diuretic,)

        -  serum creatinine (SCr) (mg/dl) from 3 months prior to ICU admission through up 28 days
           after admission

        -  fraction of inspired oxygen (FiO2) (%) from day 1 through day 7 (at the most) of ICU
           admission

        -  total fluid in (mL) from day 0 through day 7 (at the most of ICU admission)

        -  total fluid out (mL) from day 0 through day 7 (at the most of ICU admission)

        -  total urine output (mL) from day 0 through day 7 (at the most of ICU admission)

        -  urine output per 12-hour shift (mL/hr) from day 0 through day 7 (at the most of ICU
           admission)

        -  use of renal replacement therapy (RRT) (yes/no)

        -  modality of RRT when available

        -  use of ventricular assisted devices or extracorporeal Membrane Oxygenation (ECMO)

        -  outcome data

             -  mortality

             -  PICU length of stay

             -  hospital length of stay

      Calculated daily values include:

        -  Change from baseline creatinine calculated as = Daily Cr/Baseline Cr

        -  AKI stage per Kidney Disease Improving Global Outcomes (KDIGO) guidelines

             -  Stages 1,2 ,3 assessed by both creatinine and urine output (Table-1)31

             -  % Fluid overload: cumulative PICU fluid overload percentage (% FO), calculated as =
                ((total PICU Fluid in (L) - total PICU fluid out (L)) / PICU admit weight (kg))*100

        -  urine output per kg per 8 hour interval

        -  Renal angina index (RAI) will be assessed on Days 0 and 1.

        -  RAI = composite of risk strata and AKI clinical injury score

           o Risk strata (AKI risk tiers):

        -  1 (moderate risk): This stratum include all patients admitted to PICU and not fulfilling
           the criteria of high risk or very high risk strata

        -  3 (high risk): This include all patients with history of solid organ or bone marrow
           transplantation (BMT)

        -  5 (very high risk): This include all patients who receive both invasive mechanical
           ventilatory support AND vasoactive medication at any time in the first 12 hours of ICU
           admission.

           o AKI Clinical Injury scores:

        -  1 (ICU status and no increase from baseline creatinine or <5% fluid overload FO)

        -  2 (> 5% FO or change from baseline creatinine of 1-1.49x)

        -  4 (>10% FO or increase from baseline creatinine of 1.5-1.99x)

        -  8 (>15% FO or increase from baseline creatinine of >= 2x).

      RAI = Risk score X Injury Score The range of indices is therefore: 1, 2, 3, 4, 5, 6, 8, 10,
      12, 20, 24, and 40. RAI >= 8 indicates fulfillment of renal angina ( Basu et al5)

      Urine samples: The collection of urine samples is optional for the participating sites. The
      urine samples will be collected in the morning between 6 and 10 A.M. and/or in the afternoon
      between 3 and 7 P.M. for up to four days (day 0 through day 3) on all enrolled patients. Some
      centers may collect daily urine samples, others may choose to collect samples in both time
      windows. Urine will be drained only from the collection apparatus of an indwelling urinary
      drainage system or intermittent catheterization. Patients will not be bagged or catheterized
      separately/independently for the purposes of this study. Collected urine samples will be kept
      on ice or in 4° C refrigerator until they are processed. During processing, specimens will be
      centrifuged at 4°C for fifteen minutes. The supernatant will then be divided into up to nine
      1-mL aliquots depending on the collected urine volume and stored at minus 80°C. The stored
      urine samples from all participating sites will be shipped to the Center for Acute Care
      Nephrology Biomarker Core Laboratory in the Division of Nephrology and Hypertension at
      Cincinnati Children's Hospital Medical Center when the coordinating site request the samples
      to be shipped at the time point set forth by the coordinating site. The shipping supplies and
      instructions will be provided by the coordinating site.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        All medical and surgical patients admitted to the pediatric intensive care unit
      
Biospecimen description: 
      Urine samples will be collected from participating centers (pending local IRB approval)
    
Keywords: Acute kidney injury; Pediatrics; Critical Care