The goal of this supplementary proposal to the African-American Study of Kidney Disease and Hypertension (AASK) is to determine whether lead is a significant contributor to the etiology of hypertension and kidney disease in African-American men and women. Hypertension as well as chronic kidney disease have substantially higher prevalence rates among African-Americans than among other racial and ethnic backgrounds in the United States. In addition, African-Americans have higher blood lead levels and a higher prevalence of chronic lead exposure. Whether lead contributes to the etiology of hypertension and kidney disease in African-Americans is not known. To test the hypothesis that etiologic associations exist between lead, hypertension and kidney disease in African-Americans, we propose to conduct a case-control study that is both clinical in nature and epidemiological in design. Cases will be hypertensive African-Americans with renal disease, while controls will be hypertensive African-Americans with normal renal function. Bone is the depot tissue for lead in the human body, and lead deposited in dense cortical bone has a half-life that is measured in years. To measure cumulative lifetime exposure to lead in each case and control participant, we shall employ a direct, non-invasive measurement of lead in bone in vivo: 109-Cd gamma ray induced K-shell energy dispersive X-Ray Fluorescence (K-XRF). K-XRF bone lead measurements have also been shown to be a highly accurate index of lifetime lead absorption. Current lead absorption will be assessed by determination of each participant's blood lead level by atomic absorption spectrometry. This study aims to address two specific hypotheses: Hypothesis 1: Lead burden is associated with progressive renal disease in hypertensive African-Americans. Hypothesis 2: Lead burden blunts the beneficial effects of blood pressure lowering on progressive renal disease in African-Americans. If this study confirms that lead is a significant contributor to the etiology of hypertension and kidney disease in African-American men, then we shall have identified a specific environmental cause of this highly prevalent disease, a cause that is preventable. This project would not be possible without the existence of the multi-center AASK study that is currently underway at our institutions. Participants in AASK undergo extensive and comprehensive measurements of renal function; no previous study of lead exposure and renal disease has utilized such a sensitive marker of renal function
