The kidney is a key organ involved in the pathogenesis and/or course of many common clinical disorders including diabetes and hypertension. Kidney damage is a major determinant of morbidity and mortality in patients with diabetes or hypertension. In addition, inherent abnormalities within the kidneys may contribute to increases in blood pressure that in turn cause further renal damage. However, it is unclear why some patients with diabetes or hypertension suffer kidney damage whereas other patients do not. Moreover, primary abnormalities within the kidney that promote increased blood pressure in various patient populations have never been clearly defined. Although there is consensus that genetic factors contribute to individual variation in susceptibility to kidney target organ damage and to variation in the risk for hypertension, little progress has been made in identifying specific genes responsible for individual variation in renal function, susceptibility to renal damage, or the pathogenesis of high blood pressure. Accordingly, in the current studies, we will investigate the following hypothesis: the genotype of the kidney is a major determinant of renal function and the pathogenesis of hypertension. Specifically, we will determine the cardiovascular and renal effects of transplanting individual chromosome segments from a normotensive strain of rats selectively into the kidney of the spontaneously hypertensive rat (SHR). This strategy of kidney specific gene transfer will enable us to: 1) investigate the mechanisms and extent to which naturally occurring gene variation inside the kidney contributes to inherited variation in renal function and blood pressure, and 2) map specific chromosome regions that contain molecular variants expressed in the kidney that influence renal function and the risk for hypertension.
