Predictors and Impact of Low GFR After Living Kidney Donation

描述（由申请人提供）： 在过去的十年中，随着终末期肾病发病率的增加，尸体肾的数量一直停滞不前，活体肾供体的使用急剧增加。几项研究和我们的初步数据已经证明了一个子集的捐助者与意想不到的肾功能差捐赠后。因此，这些供体符合慢性肾脏疾病（CKD）的标准。目前尚不清楚活体供者低GFR的临床意义，但流行病学研究发现，CKD患者的肾功能恶化程度更严重，心血管（CV）事件数量更多;这也与肾脏和CV风险标志物的存在增加相一致。我们假设，肾脏捐赠赋予长期肾脏和心血管并发症的风险增加的一个子集的捐助者谁开发低GFR捐赠后。我们进一步假设，有特定的风险因素，发展低GFR捐赠后，捐赠前很容易识别。为了验证这些假设，我们提出了两项补充研究： 1.对捐赠后1至6年的捐赠者进行的回顾性/横断面研究。 2.一项对供体和非供体对照的前瞻性研究，随访长达5年。 我们将检查活体供者肾脏进展和心血管事件的风险因素，以确定GFR <60是否会增加供者的风险。这些将包括动态血压、尿微量白蛋白、血脂、C反应蛋白和内皮功能。这将提供关于这部分供体未来可能风险的早期数据，并深入了解CKD的风险机制。 可能增加捐献后低GFR风险的捐献者表型尚未得到充分探索，也未在种族和人种多样化的人群中进行评估。我们将评估献血后GFR <60的潜在预测因素，包括种族、民族、献血前血压和献血前体重指数。这些信息可用于建立基于证据的献血排除标准，并改善知情同意过程。 这项对活体肾脏捐赠者的研究将为不同人群中单肾切除术的医疗风险提供有价值的信息，并将有助于制定活体肾脏捐赠的数据驱动政策。 本申请的主要目的是支持候选人Elizabeth Ommen博士发展成为肾脏疾病和高血压领域的独立研究者，重点关注少数民族人群。她将补充临床研究的正式培训，她已经收到了更先进的流行病学和统计学课程。她的导师们会利用他们的研究

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