Supplemental Appendix to: Classifying Acute Kidney Injury by Urine ...

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Department of Critical Care Medicine, University of Pittsburgh School of. Medicine, Pittsburgh, PA. 3Department of ... (for patients without history of. CKD) derived ...
Supplemental Appendix to: Classifying Acute Kidney Injury by Urine Output Versus Serum Creatinine John A. Kellum1-2, Florentina E. Sileanu1-3, Raghavan Murugan1-2, Nicole Lucko1-2, Andrew D. Shaw1,4, Gilles Clermont1-2

1The

Center for Critical Care Nephrology. Department of Critical Care Medicine,

University of Pittsburgh School of Medicine, and University of Pittsburgh Medical Center, Pittsburgh, PA. 2The

CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness)

Center. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 3Department

of Biostatistics, University of Pittsburgh Graduate School of Public Health,

Pittsburgh, PA. 4Department

of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN.

Complete Methods Source Population The High-Density Intensive Care (HiDenIC)-8 database includes data on 45,655 adult patients admitted to any of 8 ICUs including medical, cardiac, transplant, surgical, neurological and trauma, within a single tertiary care academic medical center (UPMC, Pittsburgh, PA) during an 8-year period (July 2000-October 2008). For this study we applied the following exclusion criteria: 1) hemodialysis or renal transplant prior to hospital admission (n=3,762); 2) known baseline creatinine ≥ 4 mg/dl (n=105); 3) insufficient information to determine AKI status (n=499); 4) measurement of serum creatinine (SC) inadequate to stage AKI (n=491); 5) incomplete capture of urine output (UO) preventing staging of AKI (n=8,753). The remaining 32,045 patients comprised the study cohort (Figure 4). Data Collection After obtaining institutional review board approval, we de-identified data using an honest broker. We obtained data from several computerized databases. Data on all patients admitted to an ICU at UPMC from 2000 to 2008 are contained in the HiDenIC8 database. UPMC has an electronic data repository called the Medical Archival Repository System (MARS)1 containing MARS-MediPAC (i.e. demographic, clinical, insurance data), MARS-Financial (i.e. itemized billing data) and MARS-Clinical (i.e. labs, diagnostics, surgical procedures, discharge summaries). The MARS data were combined with data from the Eclypsis database, the core of inpatient electronic health records, that has ICU patients’ physiology and demographic information including blood pressure, respiration rate, temperature, heart rate, medications, fluids, mechanical ventilation, feeding, oxygen, renal replacement therapy (RRT), and

transfusions. The honest broker also obtained information from the United States Renal Data System (USRDS) and the National Death Index (NDI) and merged these results with the HiDenIC-8 database prior to de-identification. Study Cohorts We classified race as white, black and other (when race was not reported it was classified as other). Co-morbid conditions were determined by International Classification Diseases, 9th edition (ICD-9) codes. We designated patients as surgical or medical based on the diagnosis related group (DRG) at hospital admission. The APS-III score was computed from electronic abstraction of all physiologic variables comprising the acute physiology components of the APACHE III as described, assuming normality when values were missing.2 Because sepsis is underreported with ICD-9 codes, we defined suspected sepsis as the ordering of blood cultures and antibiotics within 24 hours of each other, as defined previously.3 Baseline, admission and reference serum creatinine were determined as previously described.4,5 Definitions of these values include: 1) baseline creatinine = lowest value among a. the most recent pre-hospital creatinine value up to one year prior to the index hospital admission and b. creatinine recorded in the first 24 hours of hospital admission; 2) admission creatinine = creatinine recorded in the first 24 hours of hospital admission; 3) reference creatinine = the baseline creatinine when available, otherwise the lowest between a. creatinine recorded in the first 24 hours of hospital admission; b. first 24 hours of ICU admission; and c. (for patients without history of CKD) derived from the Modification of Diet in Renal Disease (MDRD) equation for serum creatinine using a GFR of 75mL/min/1.73m2 (see table S4 for results by method).

Acute Kidney Injury Classification and Duration Patients were classified according to the maximum KDIGO criteria6 met during hospitalization using SC and UO criteria. Because we used RRT as an outcome we did not apply it as a rule to the small number of subjects that were started on RRT prior to achieving stage 3 criteria by UO or creatinine. For SC criteria, daily creatinine measures and the reference creatinine were used to determine the changes in kidney function and the maximum KDIGO stage. For UO criteria, UO was redistributed hourly provided that the gap between 2 actual values was ≤ 3 hours (i.e. if on hour 1 the urine measure was 100 and on hour 3 the urine measure was 300 we redistributed the values as follows: hour 1 – 100; hour 2 – 150; hour 3 – 150). In order to stage a patient based on UO they had to have a minimum of 6 hours of data. Duration of AKI was determined separately for SC and UO criteria. In order to determine duration of AKI using SC criteria, hourly SC was interpolated linearly from point to point provided that the gap between 2 actual values was ≤ 48 hours (patients with gaps in SC > 48 hours were excluded). Patients were grouped based on their maximum AKI stage during hospital stay based on the interpolated creatinine values and their persistence of AKI was assessed every 24 hours from the first time they reached their maximum stage. The process was repeated until SC no longer put the patient in their maximum stage (i.e the patient either recovered, dropped to a lower AKI stage, or had no more creatinine values measured). Persistence for UO was based on the hourly UO data and was assessed in the same 24 hour fashion as for the creatinine rule. The durations of oliguria required for staging (6 hours from stage 1, 12 hours for stage 2

and 24 hours for stage 3) were not including when determining persistence (i.e., duration was determined from the point at which the criterion was fulfilled). Outcome Ascertainment Our primary outcomes were provision of RRT (in hospital and as chronic therapy after discharge—see below), hospital mortality, and survival up to one year. Chronic RRT was defined by the entrance date into USRDS. Mortality at one year was determined from the National Center for Health Statistics National Death Index database or the Social Security Administration’s Death Master File. Sensitivity Analysis Prior studies have questioned whether patients with small absolute changes in serum creatinine should be included in the classification of AKI even though the relative change in creatinine meets the definition for AKI.7 This occurs when patients have very low baseline serum creatinine. For example a patient with a baseline creatinine of 0.5 mg/dl would reach stage 1 AKI at 0.75 mg/dl. To examine whether these patients are different from other patients in terms of long-term outcomes related to AKI stage, we stratified our analysis by patients with baseline serum creatinine