MECHANISMS OF HYPERTENSION AND RENAL FAILURE IN BLACKS

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We propose that black patients with hypertension who have a family member with end stage renal disease secondary to hypertension (H-ESRD) are at a high risk of also developing renal disease. Black patients whose kidneys have failed from nephrosclerosis can be used to define a high risk population. We will test the following five hypotheses: 1) The first degree relatives of patients with H-ESRD are at high risk of developing hypertension and renal insufficiency; 2) If renal dysfunction precedes hypertension, those first degree relatives who have abnormal renal hemodynamics are more likely to develop hypertension than those with normal renal hemodynamics; 3) If hypertension precedes renal disease, those first degree relatives who are documented to be hypertensive will be more likely to have detectable declines in renal function over the period of observation than those who are normotensive at the beginning of observation; 4) Abnormal renal vasodilator responses to acute L-arginine infusion will define a high-risk group of subjects that later will demonstrate detectable declines in renal function; and 5) the influence of chronic low dose exposure to lead from the environment is relevant in some families and may intensify the consequences of hypertension. The following specific aims test these hypotheses: 1) To study, prospectively, black individuals who are first degree relatives of 100 black patients with H-ESRD currently receiving dialytic support in our facility; 2) To evaluate prospectively renal vasodilator responses to acute L-arginine infusion in these black subjects, and use these responses to define specific phenotypic subsets of black hypertensive patients; 3) To evaluate body stores of lead in these subjects; 4) To correlate in prospective follow-up studies, early declines in renal function and/or development of hypertension with the initial results of renal vasodilatory responsiveness and body stores of lead; 5) To identify hypertensive sib-pairs, and to store their genomic DNA samples for RFLP, microsatellite, and linkage analysis at candidate gene loci.