The Zuni Pueblo, located in McKinley County, New Mexico, has a population of 10,000. There is an epidemic of end-stage renal disease (ESRD) at Zuni. The prevalence of ESRD at Zuni is 10.9 and 3.6 times the rates for U.S. Whites and American Indians, respectively, and is increasing at one of the fastest rates in the world. This epidemic is attributable to IgA nephropathy (IgAN) and diabetic nephropathy (DN) and provides a unique opportunity to explore risk factors for the occurrence and progression of two common causes (IgAN and DN) of ESRD at Zuni and around the world. To maximize this opportunity, the investigators established the Zuni Kidney Project (ZKP). The ZKP will use the combined resources of the University of New Mexico Health Sciences Center (UNMHSC), Indian Health Service (IHS), Center for Human Genome Studies at Los Alamos National Laboratory (CHGS@LANL), National Institutes of Health (NIH), Centers for Disease Control (CDC), Harvard University, Emory University, Johns Hopkins University, and Case Western Reserve University Schools of Medicine. The ZKP's mission is to reduce the burden of renal disease at Zuni. The ZKP has four major objectives, as follow: 1) conduct a population-based, cross-sectional survey to precisely estimate the prevalence of incipient and overt renal disease, and create a base population and DNA repository to support a future search for candidate genes in incipient cases in a planned, nested, case-control study (case-based design); 2) conduct a prevalent case-control study to identify environmental, socioeconomic, and genetic determinants of renal disease; 3) conduct a study of three cohorts (controls, incipient renal disease, and overt renal disease) to describe the natural history and identify environmental, socioeconomic, and genetic determinants for disease progression; and 4) conduct an intervention trial to compare the safety and efficacy of an angiotensin-converting enzyme inhibitor (ACEi) versus an angiotensin II receptor antagonist (AIIRA) in IgAN and DN, and its effect on the renal expression of genes implicated in disease progression. The investigators state that information gained from the intervention trial will provide valuable pilot data for planning a larger, multicenter study to compare the safety and efficacy of ACEi versus AIIRA in American Indians with renal disease.
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