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，由于终末期肾脏疾病的发病率增加，身体肾脏的数量仍然停滞不前，活体肾脏捐赠者的使用急剧增加。几项研究和我们的初步数据表明，捐赠者中有一组在捐献后肾功能出乎意料地差。因此，这些捐赠者符合慢性肾脏疾病(CKD)的标准。低GFR对活体供者的临床意义尚不清楚，但流行病学研究发现，CKD患者的肾功能恶化更严重，心血管(CV)事件更多；这也与肾脏和心血管风险标志物的存在增加不谋而合。我们假设，在捐献后肾小球滤过率较低的供者中，肾脏捐献会增加长期肾脏和心血管并发症的风险。我们进一步假设，有特定的风险因素发展成低GFR的捐赠后，很容易在捐赠之前确定。为了检验这些假设，我们提出了两项补充研究： 1.对捐献后1至6年的捐赠者进行回顾/横断面研究。 2.对捐赠者和非捐赠者对照进行前瞻性研究，跟踪时间长达5年。 我们将研究活体捐赠者肾脏进展和心血管事件的风险因素，以确定GFR&lt；60是否会使捐赠者面临更高的风险。这些指标包括动态血压、尿微量白蛋白、血脂、C反应蛋白和内皮功能。这将提供关于这一捐赠者子集未来可能存在的风险的早期数据，并提供对CKD风险机制的洞察。 可能增加捐献后低GFR风险的供者表型还没有得到很好的研究，也没有在种族和民族多样化的人群中进行评估。我们将评估捐献后GFR为60英镑的潜在预测因素，包括种族、民族、捐献前血压和捐献前体重指数。这些信息可用于建立基于证据的捐赠排除标准，并改进知情同意程序。 这项关于活体肾脏捐赠者的研究将提供关于单肾切除在不同人群中的医疗风险的有价值的信息，并将有助于制定活体肾脏捐赠的数据驱动政策。 这项申请的主要目的是支持候选人伊丽莎白·奥曼博士发展成为肾脏疾病和高血压领域的独立研究员，重点是少数群体。她将通过流行病学和统计学方面的更高级课程来补充她已经接受的临床研究方面的正式培训。她的导师将利用他们的研究

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