1/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

1/14 APOL1长期肾移植结果网络（APOLLO）临床中心

• 批准号: 10731266
• 负责人: Brad C Astor
• 金额: $ 6.03万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 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/10731266
• 关键词: Academic Medical Centers; Acceleration; Acute; Address; African American; African ancestry; Albumins; Allografting; American; Antibodies; Apolipoproteins; Bacterial Infections; Blood; Caring; Clinic; 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; Immunosuppression; Individual; Injury; Intervention; Iowa; Kidney; Kidney Failure; Kidney Transplantation; Lesion; Living Donors; Longterm Follow-up; Measures; Medical; Minnesota; Monitor; Nebraska; Organ; Outcome; Outcome Study; Participant; Pattern; Phase; Phenotype; Policies; Prevalence; Proteinuria; Public Health; Quality of life; Recurrent disease; Registries; Relative Risks; Renal function; Reporting; Research; Risk; Role; Safety; Serum; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States National Institutes of Health; Universities; Urine; Variant; Virus Diseases; Wisconsin; base; clinical center; cohort; ethnic difference; follow-up; gene interaction; genetic risk factor; genetic variant; graft failure; graft function; high risk; improved; kidney biopsy; living kidney donor; novel; post-transplant; primary outcome; programs; prospective; racial difference; recruit; risk variant; secondary outcome

PROJECT SUMMARY/ABSTRACT Recipients of a kidney transplant from an African-American deceased donor have worse outcomes than their counterparts receiving an organ from a European-American deceased donor. In addition, kidney transplants from deceased donors with two apolipoprotein L1 gene (APOL1) high-risk genotypes, which is almost exclusively found in individuals of recent African ancestry, have shorter survival. Some recipients of these organs, however, have good long-term outcomes. Therefore, we hypothesize that APOL1 genes interact with other environmental or inherited factors to cause accelerated failure of kidney transplants. Similarly, living donors of recent African ancestry face increased risk of post-donation kidney failure compared to European-American living donors, but the potential impact of APOL1 genotypes in these donors is unclear. The National Institutes of Health (NIH) established the “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) U01 Consortium in 2017 to prospectively address several questions regarding APOL1 genotyping in kidney transplantation. The APOLLO Consortium includes a Scientific and Data Research Center and 13 Clinical Centers, including our University of Wisconsin Clinical Center. In the proposed APOLLO Phase 2, we will collect extended long-term data on graft function, injury, and survival to more comprehensively define outcomes associated with donor and recipient APOL1 genetic variants and continue to recruit new living donors of African ancestry. Working with the SDRC, we will return APOL1 genotype results to enrolled transplant recipients and living donors. The data to be collected will define the impact of genotypes on graft outcomes and living donors and identify secondary factors that modify outcomes. These data are critical to improve allograft survival and quality of life for all transplant recipients.

项目概要/摘要 接受非裔美国人已故捐赠者肾脏移植的患者的结果比接受移植的患者更差 他们的同行接受了一位已故欧美裔捐赠者的器官。此外，肾 来自具有两个载脂蛋白 L1 基因 (APOL1) 高风险基因型的已故捐献者的移植物，即 几乎只存在于近代非洲血统的个体中，存活时间较短。部分收件人 然而，这些器官具有良好的长期结果。因此，我们假设 APOL1 基因 与其他环境或遗传因素相互作用，导致肾移植加速失败。 同样，近代非洲血统的活体捐赠者面临捐赠后肾衰竭的风险增加 与欧美活体捐赠者相比，但 APOL1 基因型对这些人的潜在影响 捐助者不清楚。美国国立卫生研究院 (NIH) 建立了“APOL1 长期肾脏 移植成果”（APOLLO）U01联盟于2017年前瞻性地解决了几个问题 关于肾移植中的 APOL1 基因分型。 APOLLO 联盟包括一个科学和 数据研究中心和 13 个临床中心，包括我们的威斯康星大学临床中心。在 拟议的 APOLLO 第 2 阶段，我们将收集有关移植物功能、损伤和生存的长期数据 更全面地定义与捐赠者和接受者 APOL1 遗传变异相关的结果， 继续招募新的非洲血统活体捐赠者。与 SDRC 合作，我们将归还 APOL1 向登记的移植受者和活体捐赠者提供基因型结果。要收集的数据将定义 基因型对移植结果和活体捐赠者的影响，并确定影响的次要因素 结果。这些数据对于提高所有移植受者的同种异体移植存活率和生活质量至关重要。