Living Donor Extended Time Outcomes (LETO) Study

项目总结 我们将这项题为“活体捐赠者延长的时间结局(LETO)”的建议作为辅助研究提交给新的 发起了“APOL1长期肾脏移植成果”(Apollo)网络。阿波罗联盟 代表了最雄心勃勃的国家研究，涉及捐赠者载脂蛋白L1基因的含义 (APOL1)肾脏风险变异对肾移植结果的影响。然而，父母的预期设计 阿波罗没有能力评估活体捐赠者的捐献后肾脏健康状况和受者的结局 他们的肾脏由于随访期短和长期趋势而导致数量减少 有2个APOL1肾脏风险变异体的人在最近历年捐献。我们提出了一种经济实惠的“混合动力”。 研究设计--将以家庭为基础的研究访问收集的数据与部分收集的数据进行联合分析 临床护理(已登记在国家登记处)--这将大大增加 跟进，增强学习动力。我们将招募1100名在2001-2005年间捐献的活体捐赠者 这些数据将对非裔美国人活体肾脏捐赠的临床实践产生重大影响。我们的 具体目标是： 目标1：在具有全国代表性的样本中确定非洲裔美国人活体肾脏捐赠者是否有2 APOL1肾病风险变异患上临床上有意义的慢性肾脏疾病的风险更高(估计 肾小球滤过率&lt；45ml/min/1.73m2)，大约在捐赠后20年。 目的2：确定其他独立的(或APOL1交互的)基因变异是否与 临床重大慢性肾脏疾病的风险(估计的肾小球滤过率和lt；45ml/min/1.73m2) 非裔美国人活着的肾脏捐赠者。 目的3：确定供者APOL1肾脏风险变异和其他新的遗传风险因素对移植肾的影响 具有全国代表性的活体供肾移植受者的存活率和受者结局 来自活着的非裔美国人捐赠者。

PROJECT SUMMARY We submit this proposal titled “Living donor Extended Time Outcomes (LETO)” as an ancillary study to the newly initiated “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) Network. The APOLLO Consortium represents the most ambitious national study addressing the implications of donor apolipoprotein L1 gene (APOL1) renal-risk variants on kidney transplant outcomes. However, the prospective design of the parent APOLLO is underpowered to assess postdonation kidney health in living donors and outcomes in recipients of their kidneys due to due to short follow-up duration and secular trends resulting in diminishing numbers of persons with 2 APOL1 renal-risk variants donating in recent calendar years. We propose a 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 will greatly increase the number of person-years of follow-up and enhance study power. We will enroll 1,100 living donors who donated from 2001-2005 to generate data that will have a major impact on the clinical practice of living kidney donation in African Americans. Our specific aims are: Aim 1: To determine in a nationally representative sample whether African American living kidney donors with 2 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. Aim 2: To determine whether other independent (or APOL1 interactive) gene variants associate with increased risk of clinically significant chronic kidney disease (estimated glomerular filtration rate <45 ml/min/1.73m2) in African American living kidney donors. Aim 3: To determine the impact of donor APOL1 renal-risk variants and other novel genetic risk factors on graft survival and recipient outcomes in a nationally representative sample of living donor kidney transplant recipients from African American living donors.