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 肾脏供体轮廓指数（KDPI）结合了已知影响同种异体移植存活的因素。他们之中， 非洲种族是一个被认为会对移植结果产生不利影响的变量。载脂蛋白L1的风险变体 （APOL1）基因最近与非洲血统个体的慢性肾脏疾病有关。 回顾性数据表明，捐赠者中存在两个APOL1风险变体可能会影响长期 同种异体结果。这些数据将需要在非洲人的捐助者中的潜在队列和研究中得到验证 祖先，包括非洲血统的独特人群，我们的网络将捕获 设计（佛罗里达州/波多黎各/美国维尔京群岛）。本应用的目标1将验证长期移植结果 在来自死者和非洲血统的生物捐助者的器官中，带有两个Apol1风险变体 与少于两个风险变体相比。 AIM 2将比较拉丁美洲人之间的接收者结果 非洲血统和黑人（非洲裔美国人和非洲加勒比海）以及捕获潜力 与供体，​​受体和移植相关的“第二次命中”的相互作用。 AIM 3将重点放在临床上 携带两个Apol1风险变体的个人捐赠的后果，并将发展转化 研究APOL1生物学的工具将与Apollo网络和科学界共享。 我们与一支由跨学科和跨机构合作者组成的独特团队，其中包括五个 器官采购恢复机构以及为佛罗里达州，波多黎各和的八个移植中心 美国维尔京群岛以及UNOS的支持。此外，我们正在与由A的遗传学家合作 NIH-U54赠款专注于潜水者患者人群的遗传研究。为了利用我们的专业知识，我们有 在Apol1生物学/遗传学领域以及我们的临床和我们的临床和 翻译科学研究所。这些关系以及我们以前在大型中心方面的专业知识 纵向人群，例如海王星和治疗，将有助于成功地开发这项研究 国家一级。