Kidney Tubular Injury and Dysfunction and Racial Disparities in Incident Hypertension and Kidney Function Decline
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PROJECT SUMMARY The overarching goal of this competitive revision application is to extend the mission of the University of Alabama at Birmingham-University of California, San Diego O'Brien Center for Acute Kidney Injury (AKI) Research (P30) by examining factors that contribute to racial disparities in kidney-related health outcomes, which are disproportionately represented in the Southeastern US. Black Americans are at higher risk for hypertension (HTN) and chronic kidney disease (CKD) than white Americans. The public health implications of these disparities are enormous. It is estimated that over half of the elevated risk of heart disease, stroke and death in black Americans compared with white Americans is attributable to their higher lifetime prevalence of HTN and CKD. This places prevention of HTN and CKD among the most important public health priorities for addressing racial disparities in cardiovascular disease and mortality. However, efforts to develop effective strategies are hampered by a limited understanding of why black Americans experience higher rates of HTN and CKD. This is particularly important at younger ages because HTN and CKD manifest earlier in black Americans. Kidney tubules play a central role in the regulation of blood pressure and glomerular filtration rate (GFR). Tubular atrophy and interstitial fibrosis disrupt numerous biologic processes related to blood pressure control and glomerular filtration, contributing to the onset of HTN and GFR decline. Our group and others have shown that serum and urine measures of tubule health associate with the development of HTN and CKD progression in select populations. Further, in older age groups, we have preliminary data that suggest black adults have greater tubular injury and dysfunction than white adults as measured by serum and urine markers. However, these prior studies were limited by focusing on older populations or those with established co-morbidities, making it unclear how tubular injury may develop in younger, healthier adults, and whether early damage to the kidney tubules contributes to the disproportionate development of HTN and CKD in black as compared to white adults. The Coronary Artery Risk Development in Young Adults (CARDIA) Study provides an ideal opportunity to examine associations of markers of kidney tubule health with the development of HTN and CKD in younger adults, and recruited participants in the Southeast US, among other areas. The goals of this application are to (1) determine racial differences in biomarkers of kidney tubule injury and dysfunction and to identify whether unique patterns of kidney damage are more common in black than in white adults; (2) examine the association of novel markers of kidney tubule health with risk of incident HTN and rapid eGFR decline; and (3) quantify the contribution of abnormalities in kidney tubule health to the observed racial disparities in HTN and CKD among CARDIA participants. This competitive revision application will substantially add to the ongoing work of our center by identifying novel factors associated with racial disparities in the burden of HTN and CKD.
