This project will examine the long-term health risk for people who have been living kidney donors. The primary focus will be on Caucasians and African Americans who have undergone donor nephrectomy though data from donors from other ethnic backgrounds will also be obtained. Donor health will be compared to that of specific cohorts of non-donors. With waiting times for deceased donor organs approaching 5 years, living donor transplants now account for 40% of kidney transplants nationwide. Incomplete and limited follow-up may underestimate the true long-term morbidity and mortality of living kidney donation, particularly as national trends indicate approval of older, more obese donors. The overall hypothesis for this project is that Caucasian and African American living kidney donors, when compared to individuals who are not kidney donors, have: (a) Lower or the same incidence of renal failure, cardiovascular (CV) events and death, (b) Lower or the same level of risk for renal and CV disease and (c) Better or the same quality of life. To test this hypothesis, kidney donors will be studied at two sites (predominantly Caucasian donors at Mayo Clinic, Rochester, MN;Caucasian and African American donors at the University of Alabama, Birmingham, AL). Comparison controls for the study will be spouses and siblings of each donor and, for a subgroup, community control subjects from the Rochester Epidemiology Project, Olmsted County, MN, and the Jackson Heart Study, Jackson, MS. The study will be carried out by a multidisciplinary team with extensive experience in clinical research and donor follow-up. The research plan will: (a) Identify all living kidney donors;determine the incidence of renal failure, CV and overall deaths and compare observed to expected event rates using community-based and national estimates, (b) Recruit all surviving renal donors (2 or more years after donation) and controls to screen for the presence of CV risk factors and measure surrogate markers for renal and CV disease, (c) Carry out glomerular filtration rate (GFR) measurements using iothalamate clearance on donors returning for in-center follow-up and examine the relationship between GFR and extent of CV disease or levels of CV surrogate markers, (d) Determine the impact of renal donation on long-term quality of life. Key strategies will be: (i) Retrospective identification and search for events on all donors, (ii) In-center or mailed health update including examination and laboratory testing, i) Analysis of CV risk by measured GFR with comparison to renal disease patients, (iv) Quality of life assessment, (v) Evaluation results for donors and spouse, sibling and community controls will be compared.