BACKGROUND:

Although hypertension is a predisposing factor for end stage renal disease, the underlying hypothesis of this study was that in select African-American families genetic factors predisposed them to develop ESRD in the face of hypertension. An inherited basis for H-ESRD was supported by familial clustering of H-ESRD among African Americans that could not be explained by socioeconomic status, access to medical care, and the prevalence of diabetes and hypertension.

DESIGN NARRATIVE:

DNA samples were collected, identified, and clinically characterized from African-American sib-pairs (and other family members with hypertensive end-stage renal disease). This aspect of the study was based on the fact that Dr. Freedman, the principal investigator, had already developed a unique "family history of end-stage renal disease" database independently funded by the End-Stage Renal Disease Network Six. This registry served as a very large and unique collection of African-American end-stage renal disease patients. He began with a candidate gene approach for linkage to hypertensive end-stage renal disease in his patient samples using a variety of growth factor genes, genes involved in sodium transport and vascular tone, as well as human homologues of rodent genes that had, or were to be identified in the future as contributing to ESRD in that organism. If this initial first pass of candidate genes failed to demonstrate linkage to hypertensive end-stage renal disease, a systematic genome-wide scan was to be performed with available simple sequence length polymorphisms (SSLP) and other polymorphic markers. Hypertensive end-stage renal disease is a condition of enormous clinical and economic importance and identification of associated or causative renal-failure genes would form a genetic basis for the detection of high-risk individuals and assist in development of intervention and treatment strategies to prevent this condition.