Genetic Determinants of Outcomes in Acute Kidney Injury

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): AKI is defined as a reduction in kidney function of abrupt onset that is characterized by a fall in glomerular filtration rate usually detected by a corresponding rise in serum creatinine. AKI is among the strongest risks for increased morbidity and mortality observed in acutely ill, hospitalized patients, and may also be an important risk factor for development and progression of chronic kidney disease to end-stage renal disease. While AKI has long been known to be associated with high short term morbidity and mortality, it has traditionally been thought to be a self-limited disease process, with no long term clinical sequelae in survivors. This view has been dramatically altered in recent years, as accumulating data strongly suggests that survivors of AKI are at enhanced risk of developing progressive chronic kidney disease (CKD) with associated risk of further progression to end stage renal disease. Moreover, both AKI and CKD may be independent risk factors for cardiovascular disease events. Though short-term consequences have been extensively studied, there have been no studies prospectively examining long-term outcomes in survivors of AKI relative to at-risk controls. There is a great need for rigorous prospective assessment of the natural history of AKI with careful longitudinal follow up and with robust biosample collection to further inform disease mechanisms. In response to these concerns, in 2008, the NIDDK initiated the prospective Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study to enroll hospitalized adults and children with and without AKI. The overarching goals of ASSESS-AKI are to delineate the natural history of AKI, the impact of varying severity of AKI on renal, cardiovascular and other clinical and patient-centered outcomes, as well as to identify predictors of adverse events after an episode of AKI. There is also a need for new molecular and genetic markers of risk for poor outcomes in AKI to identify patients who might benefit from more aggressive care or new therapies and to elucidate the underlying pathologic mechanisms responsible for this progression. This renewal application proposes to continue the University of Washington (UW) site as part of the ASSESS-AKI Consortium, to add new measurements of biomarkers relevant to key ASSESS-AKI outcomes, and to enhance planned genetic analyses. We have established a multidisciplinary investigative team with expertise in acute kidney injury, critical care medicine, bioinformatics, and techniques for genetic analysis. The UW site participation is a unique resource of great utility for the ASSESS-AKI Consortium.