MECHANISMS OF HYPERTENSION AND RENAL FAILURE IN BLACKS

我们建议有家庭成员的黑人高血压患者 继发于高血压的终末期肾病（H-ESRD）的患者 患肾病的风险也很高。 黑人患者的肾脏 肾硬化失败可用于定义高风险 人口 我们将测试以下五个假设：1）第一个 H-ESRD患者的一级亲属处于发展的高风险中， 高血压和肾功能不全; 2）如果肾功能不全先于 高血压，肾功能异常的一级亲属 血液动力学比那些 肾血流动力学正常; 3）如果高血压先于肾病， 那些被记录为高血压的一级亲属将 更有可能有可检测到的肾功能下降， 观察期内血压正常的人比观察开始时血压正常的人 观察; 4）对急性L-精氨酸的异常肾血管舒张反应 输注将定义一组高风险受试者， 显示可检测的肾功能下降;和5）影响 长期低剂量暴露于环境中的铅， 有些家庭，可能会加剧高血压的后果。 的 以下具体目标验证了这些假设：1）为了学习， 前瞻性地，黑人个体谁是一级亲属的100 在我们的研究中，目前接受透析支持的H-ESRD黑人患者 2）前瞻性评价肾血管舒张反应， 在这些黑人受试者中进行急性L-精氨酸输注， 对定义黑色高血压的特定表型子集的反应 3）评估这些受试者体内铅的储存量; 4） 在前瞻性随访研究中， 高血压的功能和/或发展，初步结果为 肾血管舒张反应性和铅的体内储存; 5）识别 高血压同胞对，并储存他们的基因组DNA样品用于RFLP， 微卫星和候选基因位点的连锁分析。

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.