Trajectory of post-donation renal function in living kidney donors

 描述(申请人提供)：在美国，每年约有6000名健康的人接受活体供肾切除手术，以造福于所爱的人甚至陌生人。肾脏捐赠者面临的直接风险很低，而且众所周知。然而，捐赠者的长期安全性最近受到了质疑，大型国家研究报告称，肾脏捐赠者的终末期肾病(ESRD)发生率较高。鉴于这些健康的人正在为他人的利益进行手术，而对自己没有任何好处，了解肾脏捐赠者是如何进展到ESRD的，以及哪些捐赠者可能是ESRD进展的最大风险，这一点至关重要。使用估计的肾小球滤过率(EGFR)评估捐献后的肾功能轨迹可能会显示肾功能衰竭的进展。我们也许能够通过在不同的高危捐赠者群体中模拟捐献后EGFR的轨迹来证明哪些捐赠者患ESRD的风险最大。在美国，患有高血压(HTN)和/或糖尿病(DM)的患者患ESRD的风险更高。少数肾捐献者在捐献时患有HTN或DM；然而，肾捐献者在捐献后发生HTN的风险更高。此外，与白人捐赠者相比，非裔美国捐赠者患HTN和DM的风险更高。更常见的共病是肥胖：超过五分之一的在世肾脏捐赠者在捐赠时肥胖。虽然短期内 随访被证明是安全的，捐献后较高的体重指数与较低的EGFR和HTN相关。这项建议将研究患有HTN、DM或在捐献时肥胖的捐赠者的EGFR的轨迹，以评估这些群体是否有更高的ESRD风险。为了实现这一点，我们将利用一项正在进行的、由R01资助的大型多中心研究来解决以下问题：1)模拟发生捐赠后HTN后活体肾脏捐赠者的肾功能轨迹，进一步分析种族对EGFR轨迹的影响；2)模拟发生捐赠后DM后捐赠者的肾功能轨迹。 进一步分析种族因素的影响；3)建立供者肾功能的轨迹模型 捐献时肥胖的人，并进一步分析种族的影响。考虑到父母研究的丰富的一次数据收集和二次数据联系，这些目标是高度可行的。这项辅助研究的独特贡献将是对每个高风险捐赠者群体中的EGFR轨迹进行数据建模。我们假设捐献时的肥胖、捐献后HTN的发病率和捐献后DM的发病率将与随后的肾功能下降相关，在每组中，非裔美国捐赠者将比白人捐赠者面临更高的风险。更好地了解肥胖、糖尿病、HTN和种族在捐赠者中的相互作用将有助于指导临床医生更好地选择捐赠者，促进活体肾脏捐赠者在手术风险和捐赠后结果方面的知情同意，并为捐赠者提供护理以确保最佳结果。

 DESCRIPTION (provided by applicant): Every year, about 6000 healthy individuals undergo live donor nephrectomy in the United States to benefit a loved one or even a stranger. Immediate risks to kidney donors are low and well-understood. However, long- term donor safety has recently come into question, with large national studies reporting higher incidence of end stage renal disease (ESRD) in kidney donors. Given that these are healthy individuals undergoing an operation for the benefit of another person, at no benefit to themselves, it is vitally important to understand how kidney donors progress to ESRD and which donors might be at greatest risk of ESRD progression. The trajectory of renal function after donation using estimated glomerular filtration rate (eGFR) may show progression of renal failure. We may be able to demonstrate which donors are at greatest risk of ESRD by modeling the trajectory of eGFR after donation within different at-risk groups of donors. In the US, patients with hypertension (HTN) and/or diabetes mellitus (DM) are at higher risk for ESRD. A small minority of kidney donors has HTN or DM at time of donation; however, kidney donors have a higher risk of developing HTN after donation. Further, African American donors had a higher risk of developing HTN and DM compared to Caucasian donors. A more common comorbidity is obesity: over one-fifth of living kidney donors are obese at the time of donation. While short-term follow up has been shown to be safe, higher body-mass index is associated with lower eGFR and HTN post-donation. This proposal will study the trajectory of eGFR in donors who develop HTN, develop DM, or are obese at time of donation in order to evaluate whether these groups are at higher risk for ESRD. To accomplish this, we will leverage a major, ongoing, R01-funded, multicenter study to address the following: 1) to model the trajectory of renal function in living kidney donors after incident post-donation HTN, with further analysis of effect of race on eGFR trajectory; 2) to model the trajectory of renal function in donors after incident post-donation DM, with further analysis of effect of race; and 3) to model the trajectory of renal function in donors who are obese at time of donation, with further analysis of effect of race. These aims are highly feasible given the rich primary data collection and secondary data linkage of the parent study. The unique contribution of this ancillary study will be data modeling for eGFR trajectory within each at-risk group of donors. We hypothesize that obesity at time of donation, post-donation incidence of HTN, and post-donation incidence of DM will be associated with subsequent decline in kidney function, and that African American donors will be at higher risk for this declin than Caucasian donors within each group. Better understanding the interplay between obesity, DM, HTN, and race in donors will help guide clinicians to better select candidates for donation, to facilitate informed consent of living kidney donors both in operative risks as well as post-donation outcomes, and to provide care to donors to ensure optimal outcomes.