APOL1 Long-Term Kidney Transplantation Outcomes-Consortium for the Responsible and Ethical Evaluation of Organ Donation (APOLLOCREED)Clinical Center

APOL1长期肾移植结果-器官捐献负责任和道德评估联盟（APOLLOCREED）临床中心

• 批准号: 9594467
• 负责人: Daniel Conlon Brennan
• 金额: $ 27.78万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-10-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9594467
• 关键词: APOL1; Long; Term; Kidney; Transplantation

Project Summary Two coding sequence genetic variants in APOL1 commonly found in people of Western Sub-Saharan Africa ancestry (SSAA) are associated with kidney diseases such as Focal Segmental Glomerulosclerosis (FSGS), Hypertension Attributed-End Stage Kidney Disease, and HIV-Associated Nephropathy(HIVAN). The presence of 2 APOL1- risk alleles in SSAA deceased donors is associated with 2-to-4-times higher risk of renal graft loss in the recipient. Living donors with APOL1 risk alleles may be at risk for kidney disease and excluded from donating. This application seeks to establish a large consortium of Organ Procurement Organizations (OPO) and Transplant Centers called the APOLLO-CREED—APOL1 Long-term Outcomes-Consortium for Responsible and Ethical Evaluation of organ Donation to: 1) define the outcomes of transplantation from a donor with 2 APOL1 risk alleles to guide clinical and cost-effective organ use, and define the health outcomes of living donors according to APOL1 genotype to guide living donor selection; 2) quantify outcomes of non- renal (e.g. liver) organs transplanted from donors with two APOL1 risk alleles; and 3) inform the ethical foundation of APOL1 testing for deceased donor allocation and living donor selection. To accomplish these goals, the APOLLO-CREED will consist of over 10 Organ Procurement Organizations and over 20 large and small volume, adult and pediatric Transplant Centers, from a wide geographical area to collect blood and clinical data from living and deceased donors of African Ancestry (AA) and from recipients of organs from these donors. Biospecimens for APOL1 genetic analysis will be mailed directly to the Data Coordinating Center (DCC). Clinical outcomes of all recipients of organs from donors at risk for APOL1 alleles will be ascertained through linkage to data already collected by the United Network of Organ Sharing (UNOS) as captured in the Scientific Registry of Transplant Recipients (SRTR) databases and uploaded to the DCC. Health outcomes for living donors/candidates will be integrated through linkage to the new SRTR “Living Donor Collective.” Cost data linked to the SRTR are also available and will be used to support cost-effectiveness analyses that could inform national allocation policy. A bioethicist with transplant experience will assist in the design and performance of the study and aid in the translation of the results to widespread clinical use. This efficient study design requires minimal time, effort, and cost from OPOs and Transplant Centers.

项目概要 APOL1 中的两个编码序列遗传变异常见于西撒哈拉以南非洲地区的人群 血统（SSAA）与肾脏疾病有关，例如局灶节段性肾小球硬化症（FSGS）， 高血压归因于终末期肾病和 HIV 相关肾病 (HIVAN) 的存在。 SSAA 已故捐献者中 2 个 APOL1- 风险等位基因与肾移植物丢失风险增加 2 至 4 倍相关 具有 APOL1 风险等位基因的活体捐赠者可能有患肾脏疾病的风险，因此被排除在外。 该申请旨在建立一个大型器官获取组织（OPO）联盟。 和移植中心称为 APOLLO-CREED—APOL1 长期成果联盟 对器官捐赠进行负责任和道德的评估，以： 1) 确定器官移植的结果 具有 2 个 APOL1 风险等位基因的捐赠者可指导临床和具有成本效益的器官使用，并确定健康结果 根据 APOL1 基因型对活体捐赠者进行分类，以指导活体捐赠者的选择；2) 量化非活体捐赠者的结果； 从具有两个 APOL1 风险等位基因的捐赠者移植的肾脏（例如肝脏）器官；以及 3) 告知伦理； 为已故捐献者分配和活体捐献者选择提供 APOL1 测试的基础。 目标，APOLLO-CREED 将由 10 多个器官采购组织和 20 多个大型和 小型成人和儿童移植中心，从广泛的地理区域收集血液和 来自非洲血统 (AA) 的活着的和已故的捐赠者以及来自非洲血统的器官接受者的临床数据 这些用于 APOL1 基因分析的生物样本将直接邮寄到数据协调中心。 (DCC) 将确定所有来自有 APOL1 等位基因风险的捐献者的器官接受者的临床结果。 通过链接到联合器官共享网络（UNOS）已收集的数据（如 移植受者科学登记 (SRTR) 数据库并上传至 DCC 健康结果。 活体捐赠者/候选人将通过与新的 SRTR“活体捐赠者集体”的联系进行整合。 还可以获得与 SRTR 相关的数据，这些数据将用于支持成本效益分析， 具有移植经验的生物伦理学家将协助设计和制定国家分配政策。 研究的表现并有助于将结果转化为广泛的临床应用。 设计需要 OPO 和移植中心最少的时间、精力和成本。