8/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

项目概要/摘要 数据表明，来自非裔美国人（AA）已故供体的移植肾与以下疾病相关： 相对于来自非AA供体的肾脏，存活率降低。其他数据表明， APOL 1风险变异，仅在AA个体中发现，与风险增加有关。 一般AA人群中CKD/ESRD的发生率。该基因的两种风险变体在AA中的患病率为13%， 可能是导致移植失败的部分或全部原因。也有传闻说， 具有两种APOL 1风险变体的肾脏捐献者发展ESRD引起了进一步的关注。第一阶段 来自已故或活着的AA肾脏供体的APOLLO研究接受者被招募到一个多中心 明确阐述APOL 1变异体对肾移植结局影响的观察性研究， 捐赠者健康埃默里APOLLO临床联盟（CC 8）由5个移植项目组成，位于 格鲁吉亚和德克萨斯。根据地理位置和转诊模式，这些计划始终提供移植 照顾大量的AA人群。作为一个例子，最新的方案具体报告发布的 SRTR表明，在2021年，在埃默里移植中心等待的个人中有65.2%是AA （全国为31.8%），65.6%的移植是在AA受体（33.7%）。 国）。在APOLLO研究的I期，CC 8招募了212名来自AA供体的肾脏接受者， 占APOLLO研究的13个临床中心和4个核心项目总入组人数的8.6%。 我们已经从100%的这些接受者中收集并提交了DNA样本用于APOL 1基因分型， 分别从98.4%和96.9%的受者中采集了血液和尿液样本。我们 还收集了97%的受试者的研究指定的临床和人口统计数据。拟议 在APOLLO研究的第二阶段，我们将对入组受试者的随访延长至研究的第4年。 奖这将要求所有受试者重新同意，允许我们收集新的血液和尿液生物样本 以及收集临床数据和测量肾功能和蛋白尿。我们还将提供 对入组受者进行的任何移植肾活检和未染色活检载玻片的结果， 未来的研究。我们相信，我们对阿波罗联合体的继续贡献将有助于 该研究的最终目的是确定APOL 1风险变异在肾脏疾病长期结局中的作用， 移植和活体肾脏捐赠。

Project Summary/Abstract Data demonstrate that transplanted kidneys from African American (AA) deceased donors are associated with reduced survival relative to kidneys from non-AA donors. Additional data demonstrate that the presence of two APOL1 risk variants, that are found exclusively in AA individuals, have been associated with an increased risk of CKD/ESRD in the general AA population. Two risk variants of this gene have a prevalence of 13% in AAs and may account for some or all of the increased risk of transplant loss. There are also anecdotal reports of AA living kidney donors with two APOL1 risk variants developing ESRD raising further concerns. In the first phase of the APOLLO study recipients of kidneys from deceased or living AA kidney donors were enrolled in a multi-center observational study to definitively address the impact of APOL1 variants on kidney transplant outcomes and donor health. The Emory APOLLO Clinical Consortium (CC8) is comprised of 5 transplant programs located in Georgia and Texas. Based on geography and referral patterns these programs consistently provide transplant care to a large population of AAs. As an example, the most recent Program Specific Report released by the SRTR demonstrated that in 2021 65.2% of the individuals waitlisted at the Emory Transplant Center were AAs (versus 31.8% nationally) and 65.6% of the transplants performed were in AA recipients (versus 33.7% nationally). In phase I of the APOLLO study CC8 enrolled 212 recipients of kidneys from AA donors representing 8.6% of the total enrollment of the 13 clinical centers and 4 core programs that comprise the APOLLO study. We have collected and submitted DNA samples for APOL1 genotyping from 100% of these recipients and have collected initial of blood and urine study specimens from 98.4% and 96.9% of these recipients respectively. We have also collected study-specified clinical and demographic data from 97% of these recipients. In the proposed second phase of the APOLLO study, we will extend the follow up of enrolled subjects through the 4th year of the award. This will require all subjects to be reconsented allowing us to collect new biosamples of blood and urine as well as the collection of clinical data and measurements of renal function and proteinuria. We will also provide the results of any transplant kidney biopsies performed on enrolled recipients and unstained biopsy slides for future studies. We are confident that our continued contributions to the APOLLO consortium will contribute to the study's ultimate aim of defining the role of APOL1 risk variants in the long-term outcomes of kidney transplantation and living kidney donation.