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

项目摘要 在撒哈拉以南非洲西部人群中常见的APOL1的两个编码序列遗传变异 先证者(SSAA)与肾脏疾病有关，如局灶节段性肾小球硬化(FSGS)， 高血压归因于终末期肾病和艾滋病毒相关性肾病(HIVAN)。他的存在 在SSAA已故供者中，2个APOL1风险等位基因与肾移植失败风险增加2-4倍相关 在收件人身上。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，并被排除在 捐献。本申请旨在建立一个由器官采购组织(OPO)组成的大型联盟 和被称为Apollo-Creed-APOL1长期成果的移植中心-联盟 对器官捐赠进行负责任和道德评估：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，以指导临床和经济有效的器官使用，并定义健康结果 根据APOL1基因对活体捐赠者进行评估，以指导活体捐献者的选择；2)量化非 从具有两个APOL1风险等位基因的捐赠者移植的肾(例如肝脏)器官；以及3)告知伦理 APOL1试验用于已故供者分配和活体供者选择的基础。要实现这些目标 目标，阿波罗信条将由10多个器官采购组织和20多个大型和 体积小，成人和儿科移植中心，从广泛的地理区域采集血液和 非洲血统(AA)活着和已故捐赠者以及来自以下来源的器官接受者的临床数据 这些捐赠者。用于APOL1基因分析的生物样品将直接邮寄到数据协调中心 (DCC)。将确定所有具有APOL1等位基因风险的捐赠者器官受者的临床结果 通过链接到器官共享联合网络(UNOS)已经收集的数据， 移植受者科学登记处(SRTR)数据库并上传到DCC。的健康结果 活体捐赠者/候选人将通过与新的SRTR“活体捐赠者集体”建立联系进行整合。成本 还提供了与SRTR相关的数据，并将用于支持成本效益分析，这些分析可以 告知国家分配政策。一位有移植经验的生物伦理学家将协助设计和 执行研究并帮助将结果转化为广泛的临床应用。这项高效的研究 从OPO和移植中心进行设计只需要最少的时间、精力和成本。

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.