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

摘要 肾脏供体特征指数（KDPI）包含已知影响同种异体移植物存活的因素;其中， 非洲种族被认为是对移植结果产生不利影响的一个变量。载脂蛋白L1的风险变体 （APOL 1）基因最近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APOL 1风险变异可影响长期预后。 同种异体移植物结局。这些数据需要在未来的队列中得到验证，并在非洲国家的捐助者中进行研究。 祖先，包括非洲血统的拉丁美洲人的独特人口，这将被我们的网络捕获 设计（佛罗里达/波多黎各/美属维尔京群岛）。本申请的目的1将确认长期移植物结局 来自携带两种APOL 1风险变异体的已故和在世非洲裔捐赠者的器官接受者 与少于两个风险变量相比。目标2将比较拉丁美洲人之间的接收结果， 非洲裔和黑人（非裔美国人和非裔加勒比人）以及捕捉潜力 与供体、受体和移植相关的“二次命中”的相互作用。目标3将侧重于临床 携带两种APOL 1风险变体的个体捐赠的后果，并将发生翻译 与APOLLO网络和科学界分享ApoL 1生物学研究工具。 我们聘请了一个独特的跨学科和跨机构的合作者团队，其中包括五个 器官采购恢复机构以及八个移植中心，服务于佛罗里达，波多黎各和 美属维尔京群岛沿着，并得到联合国海洋资源共享网络的支持。此外，我们正在与遗传学家合作， NIH-U 54基金专注于不同患者人群的遗传研究。为了利用我们的专业知识，我们 聘请了ApoL 1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。这些关系沿着我们之前在大型多中心的专业知识 纵向队列，如NEPTUNE和CureGN，将有助于本研究的成功发展， 国家层面

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.