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和尸体肾脏的数量停滞不前，活体肾脏捐赠者的使用急剧增加。多项研究和我们的初步数据表明，一部分捐赠者在捐赠后肾功能异常差。因此，这些捐赠者符合慢性肾脏病（CKD）的标准。活体捐献者低 GFR 的临床意义尚不清楚，但流行病学研究发现 CKD 患者的肾功能恶化程度更大，心血管 (CV) 事件也更多；这也与肾脏和心血管风险标志物的增加相一致。我们假设，对于捐献后肾小球滤过率较低的一部分捐献者来说，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，存在导致捐赠后肾小球滤过率低的特定风险因素，这些因素在捐赠前很容易识别。为了检验这些假设，我们提出了两项补充研究： 1. 对捐赠者捐赠后 1 至 6 年的回顾性/横断面研究。 2. 对捐赠者和非捐赠者对照进行长达 5 年的前瞻性研究。 我们将检查活体捐献者肾脏进展和心血管事件的危险因素，以确定 GFR <60 是否会使捐献者面临更高的风险。这些包括动态血压、尿微量白蛋白、血脂、C 反应蛋白和内皮功能。这将提供有关这部分捐赠者未来可能存在的风险的早期数据，并深入了解 CKD 的风险机制。 可能增加捐献后 GFR 低风险的捐献者表型尚未得到充分探索，也尚未在种族和民族多样化人群中进行评估。我们将评估捐赠后 GFR <60 的潜在预测因素，包括种族、民族、捐赠前血压和捐赠前体重指数。该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流程。 这项针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，并将有助于制定数据驱动的活体肾脏捐赠政策。 此应用程序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，重点关注少数群体。她将通过更高级的流行病学和统计学课程来补充她已经接受的临床研究正式培训。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