Acute kidney injury (AKI) is defined as a rapid and often reversible decline in glomerular filtration rate. Recent data indicate that the incidence of AKI is increasing in hospitalized patients in the United States. Between 5% and 20% of critically ill patients experience an episode of AKI, and numerous studies have documented that the development of AKI in this population is a risk amplifier for short-term mortality. Though short-term consequences have been extensively studied, to date, there have been few studies examining long-term outcomes in survivors of AKI. Recently our group and others have used administrative data to demonstrate that survivors of AKI are at risk to develop or accelerate the course of chronic kidney disease, and to develop end-stage renal disease. However, at present, limited outcome data exists in prospectively followed cohorts of individuals who experience AKI, and sparse data is available providing mechanistic insight into the biologic processes and molecular mechanisms whereby episodes of AKI may contribute to the development and progression of kidney disease. Thus, there is 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. Recent evidence suggests a role for common genetic variation in determining host susceptibility to renal disease. The central hypothesis of this proposal is that common genetic variation influences susceptibility to the development of AKI the long-term risk for development and progression to CKD in survivors of AKI enrolled by the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Consortium. To examine this hypothesis, we have established a multidisciplinary investigative team with expertise in acute kidney injury, critical care medicine, trauma surgery, bioinformatics, and techniques for genetic analysis. Furthermore, we propose to leverage other large cohorts to validate genetic associations with AKI and development of CKD. This will create a unique resource of great utility for the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Consortium.
Acute kidney injury (AKI) is defined as a rapid and often reversible decline in glomerular filtration rate. Chronic Kidney Disease (CKD) is a progressive and persistent reduction in glomerular filtration for which AKI is a major predisposing risk factor. The central hypothesis of this proposal is that common genetic variation influences susceptibility to the development of AKI, recovery of kidney function after the development of AKI, and impacts long-term risk for development and progression to CKD in survivors of AKI. Identification of genetic variants altering susceptibility to these outcomes will provide novel methods for patient risk stratification and will provide insight on the molecular mechanisms underlying AKI and progression to CKD.
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