PROJECT SUMMARY We submit this application in response to RFA-DK-22-506. The North East Consortium for Transplant Outcomes in APOL1 Kidney Recipients (NECTAR), APOLLO Clinical Center 6 (CC6), is a current member of the APOLLO Consortium - a national consortium of transplant programs established in 2017, which collaborates with United Network for Organ Sharing, Association of Organ Procurement Organizations, American Society of Histocompatibility and Immunogenetics and Scientific Registry of Transplant Recipients. The goal of this consortium is to prospectively evaluate the role of APOL1 kidney risk variants on graft outcomes in kidney transplant recipients (KTRs) and kidney function of living donors (LD) with African ancestry. The APOL1 risk variants G1 and G2 have a prevalence of 30% and 8%, respectively, among African Americans (AAs). Presence of homozygous risk variants increases the risk of non-diabetic end-stage kidney disease by 7-10 fold. NECTAR/CC6 oversees 6 Engaged transplant centers, Icahn School of Medicine at Mount Sinai (ISMMS), Weill Medical College-NewYork Presbyterian (WMC-NYP), New York University Medical Center, Northwell Health, SUNY-Upstate Medical University, and 2 Non-Engaged transplant centers, SUNY- Stony Brook University Hospital and Robert Wood Johnson University Hospital. Our 8 centers have enrolled 125 recipients of deceased donor kidneys, 30 living donor recipients, and 35 living donors with African ancestry and have collected >90% the DNA for the total cohort of 190 enrollees. Our site has established regular communication to monitor CC6 enrollment and oversee biospecimen collection and data entry at our own site and that of our network centers to ensure accurate timely completion of forms. The goal of this current proposal is to continue collaboration with the APOLLO Consortium to understand the potential modifiers of graft loss associated with APOL1 kidney risk variants, identify biomarkers predictive of graft loss, and expand the database of LD with African ancestry to better define kidney donor risk. In Phase 2, we will (1) re-engage/reconsent ALL study participants enrolled in Phase 1 to collect long-term data on kidney function outcomes in KTRs and LDs, including measurement of urine albumin to creatinine ratios, (2) obtain comprehensive data on post-transplant clinical course of ALL KTRs to understand potential second hits, (3) collect additional urine and blood biospecimens beyond 1 year post-transplant and kidney biopsy slides associated with diagnostic or surveillance kidney biopsies at the main CC6 sites (ISMMS and WMC-NYP), (4) recruit new LD with African ancestry at ISMMS and WMC-NYP, and (5) collaborate with Scientific Data and Coordinating Center to return genotype results of all interested participants accurately and safely while adhering to rules of privacy of protected health information. NECTAR/CC6 will participate in the Steering Committee and develop the necessary protocols for accurate and comp...