1/13 ApoL1 Genotypes in Kidney Donors and Long-Term Outcomes in Kidney Transplant Recipients Clinical Center

1/13 肾脏捐献者的 ApoL1 基因型和肾移植受者的长期结果 临床中心

• 批准号: 9975172
• 负责人: ALESSIA FORNONI
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975172
• 关键词: APOL1 gene; Address; Affect; African; African American; African Caribbean; Alleles; Allografting; Biological; Biology; Categories; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Sciences; Code; Collaborations; Communities; Data; Development; Disease; Enrollment; Ethnic Origin; Ethnic group; Evaluation; Florida; Funding; Genes; Genetic; Genetic study; Genotype; Graft Survival; Grant; Health; Hispanics; Human; Hypertension; Incidence; Individual; Infrastructure; Institutes; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Knowledge; Latino; Link; Living Donors; Longitudinal cohort; Microalbuminuria; Molecular Profiling; Monitor; Network-based; Organ; Organ Donations; Organ Procurements; Organ Transplantation; Outcome; Patients; Population; Population Heterogeneity; Prevalence; Primates; Prospective Studies; Prospective cohort; Prospective cohort study; Proteinuria; Puerto Rico; Quality of life; Recovery; Renal function; Reperfusion Therapy; Reporting; Retrospective Studies; Risk; Sampling; Site; Southeastern United States; System; Translational Research; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States; United States National Institutes of Health; United States Virgin Islands; Urine; Variant; Waiting Lists; allograft rejection; base; clinical center; cohort; design; follow-up; genetic variant; indexing; kidney biopsy; patient population; patient subsets; podocyte; repository; risk variant; social media; tool; transplant centers

ABSTRACT The kidney donor profile index (KDPI) incorporates factors known to affect allograft survival; among them, African ethnicity is a variable considered to adversely affect graft outcome. Risk variants of Apoliproprotein L1 (APOL1) gene have been recently linked to chronic kidney disease in individuals of African ancestry. Retrospective data suggest that the presence of two APOL1 risk variants in the donor can affect long-term allograft outcomes. These data will need to be validated in prospective cohorts and studied in donors of African ancestry, including the unique population of Latinos of African Descent which will be captured by our network design (Florida/Puerto Rico/US Virgin Islands). Aim 1 of this application will validate long-term graft outcomes in recipients of organs from deceased and living donors of African descent carrying two APOL1 risk variants when compared to less than two risk variants. Aim 2 will compare recipient outcomes between Latinos of African Descent and Blacks (African Americans and African Caribbeans) as well as capture potential interactions with donor-, recipient- and transplant-related “second hits”. Aim 3 will focus on the clinical consequences of donation from individuals carrying two APOL1 risk variants and will develop translational tools for the study of ApoL1 biology to be shared with the APOLLO Network and with the scientific community. We have engaged a unique team of interdisciplinary and interinstitutional collaborators which includes five Organ Procurement Recovery Agencies as well as eight transplant centers serving Florida, Puerto Rico and the US Virgin Islands along with UNOS support. In addition, we are collaborating with geneticists funded by a NIH-U54 grant focused on genetic studies in diverse patient populations. To leverage our expertise, we have engaged world renowned experts in the field of ApoL1 biology/genetics as well as our Clinical and Translational Science Institute. These relationships along with our previous expertise in large multi-center longitudinal cohorts, such as NEPTUNE and CureGN, will aid in the successful development of this study at a national level.

摘要 肾脏捐赠者概况指数(KDPI)包含了已知的影响同种异体移植物存活的因素；其中， 非洲族裔是一个被认为会对贪污结果产生不利影响的变量。载脂蛋白L1的危险变异体 (APOL1)基因最近被认为与非洲血统个人的慢性肾脏疾病有关。 回溯性数据表明，供者中存在两个APOL1风险变异可能会影响长期 同种异体移植的结果。这些数据需要在未来的队列中进行验证，并在非洲的捐赠者中进行研究 血统，包括非洲裔独一无二的拉美裔人口，这将被我们的网络捕捉到 设计(佛罗里达/波多黎各/美属维尔京群岛)。此应用程序的目标1将验证移植的长期结果 携带两个APOL1风险变异的已故和在世非洲裔捐赠者的器官受者 与不到两个风险变种相比。AIM 2将比较受赠者的拉丁裔结果 非洲人后裔和黑人(非裔美国人和非洲加勒比人)以及捕捉潜力 与供者、受者和移植相关的“二次点击”的互动。目标3将专注于临床 携带两个APOL1风险变异的个人捐献的后果，并将发展为 将与阿波罗网络和科学界共享研究APOL1生物学的工具。 我们聘请了一支独特的跨学科和跨机构合作团队，其中包括五个 器官采购恢复机构以及八个移植中心，为佛罗里达州、波多黎各和 美属维尔京群岛以及联合国操作系统的支持。此外，我们正在与遗传学家合作，由一个 NIH-U54基金专注于不同患者群体的基因研究。为了利用我们的专业知识，我们有 聘请了APOL1生物学/遗传学领域的世界知名专家以及我们的临床和 翻译科学研究所。这些关系以及我们之前在大型多中心的专业知识 纵向队列，如海王星和CureGN，将有助于这项研究在一个 国家级。