Predictors and Impact of Low GFR After Living Kidney Donation

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DESCRIPTION (provided by applicant): In the past decade, as the incidence of end-stage renal disease has grown and the number of cadaveric kidneys has remained stagnant, there has been a dramatic increase in the use of living kidney donors. Several studies and our preliminary data have demonstrated a subset of donors with unexpectedly poor renal function post-donation. These donors thus meet criteria for chronic kidney disease (CKD). The clinical implications of low GFR in living donors is unclear, however epidemiologic studies have found that individuals with CKD have a greater deterioration in renal function and a greater number of cardiovascular (CV) events; this also coincides with the increased presence of markers of renal and CV risk. We hypothesize that kidney donation confers an increased risk of long-term renal and cardiovascular complications in a subset of donors who develop a low GFR post-donation. We further hypothesize that there are specific risk factors for developing a low GFR post-donation that are readily identifiable prior to donation. To test these hypotheses, we propose 2 complementary studies: 1. A retrospective/cross-sectional study of donors between 1 and 6 years post-donation. 2. A prospective study of donors and non-donor controls, followed for up to 5 years. We will examine risk factors for renal progression and CV events in living donors to determine whether GFR <60 places donors at increased risk. These will include ambulatory blood pressure, urinary microalbumin, lipid profile, C-reactive protein, and endothelial function. This will provide early data about possible future risks in this subset of donors, and offer insight into the mechanisms of risk in CKD. Donor phenotypes that may increase the risk of low post-donation GFR have not been well-explored, and have not been evaluated in a racially and ethnically diverse population. We will assess potential predictors of a post-donation GFR of <60, including race, ethnicity, pre-donation blood pressure, and pre-donation body mass index. This information may be used to establish evidence-based exclusion criteria for donation and to improve the informed consent process. This study of living kidney donors will supply valuable information on the medical risks of uninephrectomy in a diverse population, and will contribute to the development of data-driven policies for living kidney donation. The primary purpose of this application is to support the candidate, Dr. Elizabeth Ommen as she develops into an independent investigator in the areas of renal disease and hypertension, with an emphasis on minority populations. She will supplement the formal training in clinical research that she has already received with more advanced courses in epidemiology and statistics. Her mentors will use their research