Living Donor Extended Time Outcomes (LETO) Study

活体捐赠者延长时间结果 (LETO) 研究

• 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
• 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

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.

项目摘要 我们将此标题为“活捐赠者延长时间成果（LETO）”作为辅助研究提交给新的 启动“ APOL1长期肾脏移植结果”（Apollo）网络。阿波罗财团 代表最雄心勃勃的国家研究，以解决供体载脂蛋白L1基因的含义 （APOL1）肾脏移植结果上的肾风险变体。但是，父母的前瞻性设计 Apollo在评估捐赠者的奉献肾脏健康和接受者的成果中的能力不足 由于后续持续时间短和世俗趋势，他们的孩子导致数量减少 最近日历年捐赠了2个APOL1肾风险变种的人。我们提出了一种成本效益的“混合” 研究设计 - 综合地分析了基于家庭的研究访问的数据以及收集的数据 临床护理（进入国家注册中心） - 将大大增加人数的数量 随访并增强研究能力。我们将注册1,100名从2001 - 2005年捐赠的活捐赠者生成 对非洲裔美国人的生活肾脏捐赠的临床实践有重大影响的数据。我们的 具体目的是： 目的1：在全国代表性的样本中确定非裔美国人活着的肾脏捐赠者是否有2个 APOL1肾风险变体患有临床意义的慢性肾脏疾病的风险更高（估计） 捐赠后大约二十年后，肾小球过滤率<45 mL/min/1.73m2）。 目标2：确定其他独立（或APOL1互动）基因变体是否与增加 临床上重要的慢性肾脏疾病的风险（估计的肾小球过滤率<45 mL/min/1.73m2） 非裔美国人活肾捐赠者。 目标3：确定供体APOL1肾风险变体和其他新型遗传风险因素对移植物的影响 在全国代表性的供体肾脏移植接受者中，生存和接受者的结果 来自非裔美国人的活捐助者。