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

8/14 APOL1长期肾移植结果网络（APOLLO）临床中心

• 批准号: 10731273
• 负责人: KENNETH A. NEWELL
• 金额: $ 37.2万
• 依托单位: EMORY UNIVERSITY
• 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 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731273
• 关键词: Acceleration; Acute; Address; African American; African American population; African ancestry; Albumins; Allografting; American; Antibodies; Apolipoproteins; Award; Bacterial Infections; Biopsy; Blood; Caring; Child health care; Clinical; Clinical Data; Collection; Consent; Cost Savings; Counseling; Creatinine; DNA; Data; Decision Making; Disparity; Donor person; Education; End stage renal failure; Enrollment; Ensure; Environmental Risk Factor; European; Evaluation; Face; Failure; Future; Genes; Genetic; Genotype; Geography; Graft Survival; HLA Antigens; Health; Health Care Costs; Hospitals; Immunosuppression; Individual; Kidney; Kidney Failure; Kidney Transplantation; Lesion; Living Donors; Longterm Follow-up; Measurement; Measures; Medical; Medical center; Observational Study; Organ; Organ Donor; Outcome; Outcome Study; Participant; Patients; Pattern; Phase; Phenotype; Policies; Prevalence; Proteinuria; Public Health; Quality of life; Recurrent disease; Registries; Renal function; Reporting; Research; Risk; Role; Safety; Sampling; Serum; Site; Slide; Specific qualifier value; Specimen; Texas; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Universities; Urine; Variant; Virus Diseases; Waiting Lists; clinical center; cohort; digital pathology; ethnic difference; follow-up; gene interaction; genetic risk factor; genetic variant; graft failure; high risk; improved; kidney biopsy; living kidney donor; medical schools; novel; post-transplant; primary outcome; programs; prospective; racial difference; recruit; repository; risk variant; secondary outcome; transplant centers

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.

项目摘要/摘要 数据显示，来自非裔美国人(AA)已故捐赠者的移植肾脏与 与非再生障碍性贫血供者的肾脏相比，存活率降低。更多的数据表明，有两个 仅在再生障碍性贫血患者中发现的APOL1风险变异与风险增加有关 CKD/ESRD在普通再障人群中的分布。该基因的两个风险变异在AAS和AAS中的患病率为13% 可能是移植失败风险增加的部分或全部原因。也有关于戒酒协会生活的轶事报道 具有两个APOL1风险变异的肾脏捐赠者患上终末期肾病，引起了进一步的关注。在第一阶段， 阿波罗研究的接受者来自已故或在世的AA肾脏捐赠者在一个多中心登记 明确研究载脂蛋白1变异对肾移植结果的影响和 捐赠者健康。埃默里·阿波罗临床联盟(CC8)由5个移植项目组成，位于 佐治亚州和德克萨斯州。根据地理位置和转诊模式，这些计划持续提供移植 照顾到大量的AA人群。例如，由世界银行发布的最新计划具体报告 SRTR显示，2021年，在埃默里移植中心等待登记的个人中，65.2%是AA (全国为31.8%)，65.6%的移植是再生障碍性贫血受者(33.7%) 全国范围内)。在阿波罗研究的第一阶段，CC8招募了212名来自AA捐赠者的肾脏接受者，这些捐赠者代表 阿波罗研究的13个临床中心和4个核心项目总招生人数的8.6%。 我们已经收集并提交了100%接受APOL1基因分型的DNA样本，并已 分别从98.4%和96.9%的受者采集初始的血液和尿液标本。我们 还从97%的受助者那里收集了研究指定的临床和人口统计数据。在建议的 在阿波罗研究的第二阶段，我们将延长对登记受试者的跟进至第四年 获奖。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 以及临床数据的收集和肾功能和蛋白尿的测量。我们还将提供 在登记的受者身上进行的任何移植肾活检的结果和未染色的活检切片 未来的研究。我们相信，我们对阿波罗财团的持续贡献将有助于 这项研究的最终目的是确定载脂蛋白1风险变量在肾脏长期结局中的作用 移植和活体肾脏捐献。