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APOL 1的两种编码序列遗传变异 祖先（SSAA）与肾脏疾病如局灶节段性肾小球硬化（FSGS）有关， 终末期肾病引起的高血压和HIV相关肾病（HIVAN）。存在 SSAA死亡供体中2个APOL 1风险等位基因与2-4倍的肾移植物丢失风险相关 在接受者。携带APOL 1风险等位基因的活体供者可能有肾脏疾病的风险， 捐赠这项申请旨在建立一个大型的器官采购组织联盟（OPO）。 和移植中心称为APOLLO-CREED-APOL 1长期结局联盟， 对器官捐献进行负责任和道德的评估，以：1）从一个 具有2个APOL 1风险等位基因的供体，以指导临床和成本效益的器官使用，并定义健康结果 根据APOL 1基因型对活体供者进行评估，以指导活体供者的选择; 2）量化非 从具有两个APOL 1风险等位基因的供体移植的肾（例如肝）器官;以及3）告知伦理 APOL 1检测用于已故供体分配和活体供体选择的基础。完成这些 目标，阿波罗信条将包括10多个器官采购组织和20多个大型和 小容量，成人和儿童移植中心，从广泛的地理区域收集血液， 来自非洲器官移植（AA）活体和已故捐赠者以及来自 这些捐助者。用于APOL 1基因分析的生物标本将直接邮寄至数据协调中心 （DCC）。将确定所有接受APOL 1等位基因风险供体器官的受者的临床结局 通过与联合器官共享网络（UNOS）已经收集的数据的链接， 移植受体科学登记（SRTR）数据库，并上传到DCC。的健康结果 活体捐献者/候选人将通过与新的SRTR“活体捐献者集体”的联系进行整合。成本 与SRTR相关的数据也是可用的，并将用于支持成本效益分析，这些分析可以 为国家分配政策提供信息。具有移植经验的生物伦理学家将协助设计和 研究的性能，并帮助将结果转化为广泛的临床应用。这项有效的研究 设计需要OPO和移植中心最少的时间、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.