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.

抽象的 肾脏供体概况指数（KDPI）包含已知影响同种异体移植物存活的因素； 非洲种族被认为是对载脂蛋白 L1 的风险变异产生不利影响的一个变量。 (APOL1) 基因最近被发现与非洲血统个体的慢性肾病有关。 回顾性数据表明，供体中存在两种 APOL1 风险变异可能会影响长期 同种异体移植结果。这些数据需要在前瞻性队列中进行验证，并在非洲捐赠者中进行研究。 血统，包括我们的网络将捕获的非洲裔拉丁裔的独特群体 设计（佛罗里达/波多黎各/美属维尔京群岛）。本申请的目标 1 将验证长期移植结果。 携带两种 APOL1 风险变异的非洲人后裔死者和活体捐赠者的器官接受者 与少于两个风险变体进行比较时，目标 2 将比较拉丁美洲人之间的接受者结果。 非洲人后裔和黑人（非裔美国人和非洲加勒比人）以及挖掘潜力 与供体、受体和移植相关的“第二次打击”的互动将集中于临床。 携带两种 APOL1 风险变异的个人捐赠的后果将产生转化 与 APOLLO 网络和科学界共享的 ApoL1 生物学研究工具。 我们聘请了一支由跨学科和跨机构合作者组成的独特团队，其中包括五名 器官采购恢复机构以及为佛罗里达州、波多黎各和美国提供服务的八个移植中心 在 UNOS 的支持下，我们正在与美属维尔京群岛的遗传学家合作。 NIH-U54 拨款重点关注不同患者群体的基因研究 为了利用我们的专业知识，我们拥有。 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 这些关系以及我们之前在大型多中心方面的专业知识。 纵向队列，例如 NEPTUNE 和 CureGN，将有助于这项研究的成功开展 国家级。