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Living Donor Extended Time Outcomes (LETO) Study

活体捐赠者延长时间结果 (LETO) 研究

基本信息

批准号：
10413009
负责人：
Chi-yuan Hsu
金额：
$ 56.47万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10413009
关键词：
Address African American African American population African ancestry American Ancillary Study Apolipoproteins Biometry Calendar Caring Cessation of life Chronic Kidney Failure Communities Data Data Analyses Donor Exclusions Donor Selection Enrollment Epidemiology European Evaluation Genes Genetic Genotype Glomerular Filtration Rate Goals Graft Survival Guidelines Health Heterozygote Home Hybrids Informed Consent Kidney Kidney Diseases Kidney Failure Kidney Transplantation Knowledge Living Donors Longitudinal Studies Organ Procurements Other Genetics Outcome Outcome Study Parents Patients Persons Publishing Registries Renal function Reporting Research Research Design Research Priority Retrospective Studies Risk Safety Sampling Societies Time Transplant Recipients Transplantation Uncertainty United States National Institutes of Health Visit adverse outcome base clinical care clinical practice clinical risk clinically significant cohort cost effective design follow-up genetic risk factor genetic variant high risk improved innovation ischemic injury kidney allograft living kidney donor novel programs prospective risk variant symposium trend

项目摘要

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.

项目概要我们提交了这项题为“活体捐赠者延长时间结果（LETO）”的提案作为新的辅助研究发起“APOL1长期肾移植成果”（APOLLO）网络。阿波罗联盟代表了解决供体载脂蛋白 L1 基因影响的最雄心勃勃的国家研究 (APOL1) 肾移植结果的肾脏风险变异。然而，母公司的前瞻性设计 APOLLO 无法评估活体捐献者的捐献后肾脏健康状况以及受捐者的结局由于随访时间短和长期趋势导致肾脏数量减少最近几年进行捐赠的具有 2 个 APOL1 肾脏风险变异的人。我们提出一种具有成本效益的“混合动力” 研究设计——联合分析在家研究访问中收集的数据以及作为部分收集的数据临床护理（进入国家登记处）——这将大大增加接受治疗的人年数跟进，增强学习动力。我们将招募 1,100 名 2001 年至 2005 年期间捐赠的活体捐赠者，以产生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：在全国代表性样本中确定非裔美国人活体肾脏捐赠者是否具有 2 APOL1 肾脏风险变异具有较高的患临床显着慢性肾脏疾病的风险（估计捐赠后大约二十年，肾小球滤过率<45 ml/min/1.73m2）。目标 2：确定其他独立（或 APOL1 相互作用）基因变异是否与增加临床上显着的慢性肾脏疾病的风险（估计肾小球滤过率<45 ml/min/1.73m2）非裔美国人活体肾脏捐赠者。目标 3：确定供体 APOL1 肾脏风险变异和其他新遗传风险因素对移植物的影响活体肾移植受者全国代表性样本的存活率和受者结果来自非裔美国活体捐赠者。