Comparative Evaluation of Urinary Biological Markers for the Prognostic Stratific

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DESCRIPTION (provided by applicant): Acute renal failure (ARF) is a serious complication in hospitalized patients and is frequently associated with adverse clinical outcomes. However, ARF can also be associated with a more benign, self-limited clinical course. Patients at risk for adverse outcomes are often not easily distinguished from those with a more benign course, making the appropriate and timely application of treatment strategies a difficult task. Novel, prognostic tools that can improve risk stratification among patients with ARF are therefore urgently needed. In recent years, an increasing number of urinary biological markers of acute kidney injury have been described. Among these, the most clinically relevant urinary markers include Kidney Injury Molecule-1 (KIM-1) (a tubular dedifferentiation marker), Neutrophil Gelatinase-Associated Lipocalin (NGAL) (a tubular proliferation marker), interleukin-18 (IL-18) (a mediator of tubular ischemic injury), N-acetyl-(-D-glucosaminidase (NAG) (a tubular brush border enzyme), cystatin C and (-1 microglobulin (two markers of impaired tubular protein absorption). Although predominantly studied for the early detection of ARF, some of these markers might also predict adverse clinical outcomes among patients with established ARF, and therefore, might be useful for risk stratification. To date, no studies have evaluated the performance characteristics of the above-mentioned urinary biological markers for the prediction of adverse outcomes in patients with established ARF in a comprehensive and comparative fashion. The hypotheses to be investigated are that urinary KIM-1, NGAL, IL-18, NAG, cystatin C, and (-1 microglobulin, individually or in combination, are superior to clinical prognostic scores in predicting adverse outcomes in patients with established ARF, including dialysis requirement and hospital mortality. We will test these hypotheses in a large cohort of 300 hospitalized patients with ARF, of which over 200 have already been accrued. We will also combine urinary biological markers with or without the addition of a clinical prognostic score, and compare the performance characteristics of these combinations with that of single prognostic tests. We expect to demonstrate that individual markers are associated with adverse outcomes in patients with established ARF, and might be superior to clinical prognostic scores. We further hypothesize that a combination of two or more markers will increase prognostic accuracy for predicting adverse outcomes. The research project is achievable as two thirds of the cohort has already been enrolled, and offers important new insights into the prognostic value of urinary biomarkers for the prediction of adverse outcomes in patients with ARF. This study might provide a foundation for the development of a more reliable prognostic risk stratification tool in ARF, which will be validated externally in other ARF cohorts, and help provide a more guided therapeutic intervention for patients with ARF.