Role of established hypertension in impaired renal recovery and function post-AKI in hypertensive males and females

Acute kidney injury (AKI) is a major clinical problem of common occurrence in the U.S. affecting 20% of all hospitalized patients with mortality rates as high as 80%. With 46% of U.S. adults classified as hypertensive based on the newest guidelines, hypertension is a very common co-morbid condition with AKI. Moreover, AKI is an independent risk factor for the development of hypertension. Interestingly, the male gender is associated with greater severity and mortality following AKI, and young males have a greater prevalence of hypertension vs. age-matched females. Despite the widespread prevalence of hypertension and AKI, the impact of hypertension on the progression of renal injury post-AKI in either sex is poorly understood. Our goal is to improve our understanding of how sex and BP impact renal outcomes following AKI. Proposed studies will employ ischemia-reperfusion (IR) as an experimental model of AKI to test the central hypothesis that hypertension exacerbates IR injury leading to impaired renal recovery and promotion of chronic kidney disease (CKD) in males through activation of 12/15 lipoxygenase and increases in endoplasmic reticulum stress and tubular cell death. In contrast, greater GPx4 in females attenuates increases in 12/15 lipoxygenase promoting more rapid recovery. Studies will further determine if established hypertension increases the susceptibility to develop chronic kidney disease. IR injury is a frequent complication of critical illness and carries a significant risk of mortality predominately due to cardiovascular events. Based on the high prevalence of hypertension and AKI as co-morbid conditions, the proposed studies are in line with the mission of the AHA to build healthier lives, free of cardiovascular diseases and stroke. Coupled with the Training Plan and Career Development Plan, this Award will provide me with the expertise and skills necessary to achieve my long-term career goal to secure a tenure-track faculty position at a leading academic institution and successfully establish an independent, extramurally-funded, and innovative research program focused on hypertension and kidney research.