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U Maryland Mid-Atlantic APOLLO Research Network Omic and Clinical Center

马里兰大学大西洋中部阿波罗研究网络组学和临床中心

基本信息

批准号：
10729890
负责人：
Jonathan S Bromberg
金额：
$ 19.95万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
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/10729890
关键词：
Acceleration Acute Address African American African ancestry Albumins Allografting American Antibodies Apolipoproteins Bacterial Infections Biopsy Blood Child Classification Clinical Data Consent Cost Savings Counseling Creatinine DNA Data Disparity Donor person Education Enrollment Ensure Environmental Risk Factor European Evaluation Face Failure Genes Genetic Genotype Geography Graft Survival HLA Antigens Health Care Costs Hospitals Immunosuppression Individual Kidney Kidney Failure Kidney Transplantation Lesion Living Donors Longterm Follow-up Maryland Measures Medical Medical center Monitor Organ Outcome Outcome Study Outcomes Research Participant Pattern Phase Phenotype Policies Prevalence Proteinuria Quality of life Recurrent disease Registries Renal function Reporting Research Research Personnel Risk Role Safety Serum Site Slide Time Transplant Recipients Transplantation United Network for Organ Sharing United States National Institutes of Health Universities Urine Variant Virus Diseases Washington biobank clinical center cohort digital pathology ethnic difference follow-up gene interaction genetic risk factor graft failure high risk improved indexing kidney biopsy living kidney donor medical schools novel post-transplant primary outcome programs prospective racial difference recruit repository risk variant safety assessment secondary outcome

项目摘要

Project Summary Relative to kidneys from European American (EA) deceased donors (DDs), kidneys transplanted from African American (AA) DDs have significantly shorter graft survival. Several landmark studies revealed kidney transplants from DDs with two apolipoprotein L1 gene (APOL1) risk variants, defining APOL1 high-risk genotypes, have shorter graft survival. APOL1-associated lesions were detected in most failed grafts from these APOL1 high-risk genotype DDs. Importantly, many kidneys transplanted from DDs with two APOL1 risk variants do not fail rapidly. We hypothesize that APOL1 interacts with other environmental and inherited factors to cause early failure of DD kidney transplants (DDKT). The National Institutes of Health (NIH) established the “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) U01 Consortium in 2017 to prospectively address several critical questions regarding broad APOL1 genotyping in AA DDKT and assessing safety in AA live kidney donation. Results could transform the US policy for allocation of kidneys and lead to improved graft survival, reassignment of AA DD kidneys to lower (i.e., better) kidney donor profile index (KDPI) classification and thus lesser discard of good-quality kidneys and more kidney transplants, greater assurance of safety for living AA donors, and cost savings. In addition, the role of recipient APOL1 genotypes on transplant outcomes is controversial and APOLLO addresses this question. The APOLLO Consortium includes a Scientific and Data Research Center (SDRC) and 13 Clinical Centers (CCs), including our center. Our CC, the “10/14 APOL1 Long- term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center” at the University of Maryland School of Medicine (UMSOM) and Medical Center (UMMC) is comprised of 4 additional kidney transplant programs at the Sentara, Georgetown, George Washington, and Children’s National Hospitals. We recruited recipients of AA DD and LD kidney transplants and AA live donors during the initial phase of APOLLO. Through 9/29/22, the APOLLO SDRC and Consortium have prospectively collected DNA from a national cohort of 3604 AA DDs and are following outcomes in 4890 DDKT. The 13 APOLLO CCs consented and collected bio-samples from 2436 DDKT recipients. In APOLLO Phase 1, our University of Maryland CC enrolled 65.3% of all recipients of an APOLLO DDKT with DNA and biosamples (81 out of 124). We also recruited 32 AA LD and 28 AA LDKT recipients. In APOLLO Phase 2, the Specific Aims of our CC are to: Aim 1. To prospectively collect long-term follow-up data on all APOLLO participants. Aim 2. To provide detailed clinical data and biospecimens on APOLLO participants from our CC. Aim 3. To facilitate return of APOL1 genotype results. Impact: APOL1 genotyping has the potential to reduce the discard of good-quality kidneys from AA donors and increase the number of transplants overall. Identifying the secondary environmental or genetic factors that modify phenotypic outcomes will improve allograft survival and quality of life for all transplant recipients.

项目概要相对于来自欧洲裔美国人 (EA) 已故捐赠者 (DD) 的肾脏，移植自非裔美国人 (AA) DD 的移植物存活率明显较短。几项具有里程碑意义的研究揭示了肾脏来自具有两个载脂蛋白 L1 基因 (APOL1) 风险变异的 DD 的移植物，定义了 APOL1 高风险基因型不同，移植物存活时间较短。在大多数失败的移植物中检测到 APOL1 相关病变 APOL1 高风险基因型 DD。重要的是，许多肾脏移植自带有两个 APOL1 风险变异的 DD 不要很快失败。我们假设 APOL1 与其他环境和遗传因素相互作用，导致 DD 肾移植 (DDKT) 的早期失败。美国国立卫生研究院 (NIH) 建立了“APOL1 长期肾移植成果”(APOLLO) U01 联盟于 2017 年前瞻性地解决关于 AA DDKT 中广泛 APOL1 基因分型和评估 AA 活肾安全性的几个关键问题捐款。结果可能会改变美国的肾脏分配政策并提高移植物的存活率，将 AA DD 肾脏重新分配至较低（即更好）的肾脏供体概况指数 (KDPI) 分类，从而减少优质肾脏的废弃，增加肾移植数量，更好地保证活体 AA 的安全捐助者和节省成本。此外，受者 APOL1 基因型对移植结果的作用是有争议，APOLLO 解决了这个问题。 APOLLO 联盟包括科学和数据研究中心 (SDRC) 和 13 个临床中心 (CC)，包括我们的中心。我们的 CC，“10/14 APOL1 长- 马里兰大学学院“肾移植成果网络 (APOLLO) 临床中心” 医学部 (UMSOM) 和医疗中心 (UMMC) 包括 4 个额外的肾移植项目，位于 Sentara、乔治敦、乔治华盛顿和国家儿童医院。我们招募了 AA 获得者 APOLLO 初始阶段的 DD 和 LD 肾移植以及 AA 活体捐献者。截至 22 年 9 月 29 日， APOLLO SDRC 和联盟前瞻性地从全国 3604 名 AA DD 队列中收集了 DNA，正在关注 4890 DDKT 的结果。 13 个 APOLLO CC 同意并从 2436 个样本中收集了生物样本 DDKT 接受者。在 APOLLO 第一阶段，我们的马里兰大学 CC 招收了所有接受者的 65.3% APOLLO DDKT 包含 DNA 和生物样本（124 份中的 81 份）。我们还招募了 32 名 AA LD 和 28 名 AA LDKT 收件人。在 APOLLO 第 2 阶段，我们 CC 的具体目标是：目标 1. 前瞻性地收集长期数据所有 APOLLO 参与者的后续数据。目标 2. 提供详细的临床数据和生物样本来自我们 CC 的 APOLLO 参与者。目标 3. 促进 APOL1 基因型结果的返回。影响：APOL1 基因分型有可能减少 AA 捐献者优质肾脏的废弃率，并提高移植总数。识别改变表型的次要环境或遗传因素结果将提高所有移植受者的同种异体移植存活率和生活质量。