Living Donor Extended Time Outcomes (LETO) Study

项目总结 我们提交此竞争性修订申请是对NOT-DK-20-012的回应，以扩展我们现有的 R01DK120551项目名为“活体捐赠者延长的时间结果(LETO)”。母公司Leto Study将招募 对1100名黑人活体肾脏捐赠者进行全国抽样，以评估他们在捐赠后15-20年的健康状况。 最初申请的主要目的是在全国样本中确定黑人活体肾脏捐赠者 具有2个载脂蛋白L1基因(APOL1)的肾脏风险变异具有较高的发生临床意义的风险 慢性肾脏疾病(估计肾小球滤过率&45毫升/分钟/1.73平方米)大约20年后 捐款。“ 只有黑人捐赠者才是父母Leto研究的注册对象。在本修订版中，R01DK120551 申请，我们建议增加500名白人活体肾脏捐赠者的登记，这将把Leto转变为 研究种族差异的强大研究平台。 这一扩展将使我们能够实现一个新的目标：量化和比较临床发展的风险 捐献后大约20年，在全国范围内的黑人和 白色活体肾脏捐赠者，并量化生物(遗传的，不可改变的)与非生物的相对重要性 导致观察到的健康差距的生物(非遗传的、潜在的可改变的)因素。 我们将使用同样具有成本效益的“混合”研究设计--联合分析在家中收集的数据 研究访问以及作为临床护理一部分收集的数据(已输入国家登记)-- 大大增加了跟踪的人年数，增强了学习力。 我们相信，这项研究的结果将强烈主张采取如下政策 改进长期后续行动和向在世捐赠者提供终身健康保险的机制--有理由 这不仅是道义上的要求，也是减少在获得活体捐赠者方面的种族差距的有力工具 移植。

PROJECT SUMMARY We are submitting this competitive revision application in response to NOT-DK-20-012 to expand our existing R01DK120551 project titled “Living donor Extended Time Outcomes (LETO).” The parent LETO study will recruit a national sample of 1,100 black living kidney donors to assess their health status ~15-20 years after donation. The primary aim of the original application is to determine in a national sample whether black living kidney donors with 2 apolipoprotein L1 gene (APOL1) renal-risk variants are at higher risk of developing clinically significant chronic kidney disease (estimated glomerular filtration rate <45 ml/min/1.73m2) approximately two decades after donation.” Only black donors are targeted for enrollment into the parent LETO study. In this revision R01DK120551 application, we propose to add enrollment of 500 white living kidney donors, which will convert LETO into a powerful research platform to study racial disparities. This expansion will allow us to address a new aim: to quantify and compare the risk of developing clinically significant chronic kidney disease approximately two decades after donation in a national sample of black vs. white living kidney donors, and to quantify the relative importance of biologic (genetic, unmodifiable) vs. non- biologic (non-genetic, potentially modifiable) factors contributing to any observed health disparity. We will use the same cost-effective “hybrid” study design—jointly analyzing data collected at home-based research visits together with data collected as part of clinical care (as entered into a national registry)—that greatly increases the number of person-years of follow-up and enhances study power. We believe that findings from this study will strongly advocate for the adoption of policies such as such as mechanisms for improved long-term follow-up and provision of lifelong health insurance to living donors--justified not only as a moral imperative but also as a powerful tool to reduce racial disparities in access to living donor transplant.