This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 8/10/2007 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. Kidneys from living donors now comprise over one-third of all kidneys donated in the United States, and this number is growing steadily. Existing data suggest that long-term effects of donor nephrectomy on the health of the donor are minimal, but small sample size, retrospective data collection, imperfect measurement of outcomes, and absence of an appropriate comparison group limit the conclusions of these studies. Moreover, there are limited data evaluating donor eligibility criteria;of note, though Blacks and Hispanics are known to have a greater susceptibility to renal failure, there is virtually no data on the impact of living donation in these potentially high risk populations. Several studies and our preliminary data have demonstrated a subset of donors with unexpectedly poor renal function post-donation. We have found an incidence of glomerular filtration rate (GFR) 60 ml/min in 31% of our donors at 6-months to 1-year post-donation, and GFR has remained low in this group at further follow-up. These donors thus meet current criteria for chronic kidney disease (CKD). 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. However, the clinical implications of low GFR in living donors are unclear. We will examine risk factors for renal progression and CV events in living donors to determine whether a GFR of 60 ml/min places donors at increased risk. This will provide early data about possible future risks in this subset of donors, and offer insight into the mechanisms of risk in CKD. The incidence of GFR 60 ml/min in our living donors is higher than previously reported;this may relate to particular characteristics in our donors. 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 pre-donation characteristics that predict development of low post-donation GFR in a donor population that includes a large proportion of Blacks and Hispanics. This information could be used to establish evidence-based exclusion criteria for donation and to improve the informed consent process. We hypothesize that kidney donation confers an increased risk of long-term renal and CV 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 identifiable prior to donation. To test these hypotheses, we propose the following complementary specific aims.: 1. To assess the clinical phenotype of living donors with low GFR post-donation and to determine the association of low GFR with markers of renal and cardiovascular risk. In this aim, we will evaluate living donors between 1 and 6 years post-donation. We will retrospectively determine pre-donation phenotypes, and measure GFR and markers of renal and CV risk in a cross-sectional analysis. Our goals are to describe the prevalence of low GFR in a racially and ethnically diverse population, to determine pre-donation characteristics that may increase the odds of low GFR post-donation, and to assess the extent of alterations in markers of renal and CV risk that occur in those with low GFR post-donation. Donors who donated a kidney at Mount Sinai Medical Center after January of 2000 will be eligible, and will have a single study visit where they will undergo ambulatory BP, urine collection for microalbumin:creatinine, and blood tests for calculation of GFR and measurement of lipid profile and C-reactive protein (CRP). Pre-donation characteristics including demographic information, pre-donation BMI, and pre-donation BP will be collected from chart and database review. Donors with a post-donation GFR 60 ml/min will comprise the study group, and will be compared to those with a GFR ?60 ml/min. 2. To prospectively assess the risk factors for low post-donation GFR and the impact of low post-donation GR on changes in markers of renal and cardiovascular risk. In this aim we will prospectively study potential living kidney donors at Mount Sinai Medical Center and Columbia-Presbyterian Medical Center to describe the incidence of low GFR in a racially and ethnically diverse population, to determine the pre-donation characteristics that predict a low post-donation GFR, and to measure changes in markers of renal and CV risk in those with a low GFR post-donation. The donor populations of Mount Sinai and Columbia include a high percentage of Blacks and Hispanics and therefore will enable comparison of outcomes across race and ethnicity. Donors will be compared to a control population who do not proceed to donation for reasons other than medical exclusion, and will be followed for up to 5 years. Subjects will be evaluated pre-donation, at 6 months, 1 year, and then yearly during the study period. At each visit, subjects will undergo ambulatory BP monitoring for determination of 24-hour BP and nocturnal dipping pattern, urine for microalbumin:creatinine ratio, and blood tests for calculation of GFR and measurement of lipid profile and CRP. A sub-group will also undergo non-invasive measurement of endothelial reactivity as an exploratory sub-study.
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