Acute kidney injury (AKI) occurs in 5-7% of all hospital admissions and recent evidence has shown that even minor changes in renal function are associated with increased risk of death. In the ICU, AKI is associated with 50% mortality, a statistic which has not changed even with dialysis therapy. In fact the Acute Renal Failure Trial Network study, a combined VA and NIH sponsored dialysis dosing study, showed no change in mortality statistics when comparing dialysis dosing. Clearly new approaches are urgently needed to address this life-threatening disease. Given the fact that the VA population is aging, prone to diabetes and hypertension, AKI is a major health problem in this group. Upon completion of this VA Merit Review, investigators in the renal community will have new targets for small molecular drug discovery that should ameliorate the mortality associated with AKI.