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.
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), and 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 in an efficient study design that requires minimal time, effort, and cost from OPOs and Transplant Centers.
