Project Summary/Abstract Data demonstrate that transplanted kidneys from African American (AA) deceased donors are associated with reduced survival relative to kidneys from non-AA donors. Additional data demonstrate that the presence of two APOL1 risk variants, that are found exclusively in AA individuals, have been associated with an increased risk of CKD/ESRD in the general AA population. Two risk variants of this gene have a prevalence of 13% in AAs and may account for some or all of the increased risk of transplant loss. There are also anecdotal reports of AA living kidney donors with two APOL1 risk variants developing ESRD raising further concerns. In the first phase of the APOLLO study recipients of kidneys from deceased or living AA kidney donors were enrolled in a multi-center observational study to definitively address the impact of APOL1 variants on kidney transplant outcomes and donor health. The Emory APOLLO Clinical Consortium (CC8) is comprised of 5 transplant programs located in Georgia and Texas. Based on geography and referral patterns these programs consistently provide transplant care to a large population of AAs. As an example, the most recent Program Specific Report released by the SRTR demonstrated that in 2021 65.2% of the individuals waitlisted at the Emory Transplant Center were AAs (versus 31.8% nationally) and 65.6% of the transplants performed were in AA recipients (versus 33.7% nationally). In phase I of the APOLLO study CC8 enrolled 212 recipients of kidneys from AA donors representing 8.6% of the total enrollment of the 13 clinical centers and 4 core programs that comprise the APOLLO study. We have collected and submitted DNA samples for APOL1 genotyping from 100% of these recipients and have collected initial of blood and urine study specimens from 98.4% and 96.9% of these recipients respectively. We have also collected study-specified clinical and demographic data from 97% of these recipients. In the proposed second phase of the APOLLO study, we will extend the follow up of enrolled subjects through the 4th year of the award. This will require all subjects to be reconsented allowing us to collect new biosamples of blood and urine as well as the collection of clinical data and measurements of renal function and proteinuria. We will also provide the results of any transplant kidney biopsies performed on enrolled recipients and unstained biopsy slides for future studies. We are confident that our continued contributions to the APOLLO consortium will contribute to the study's ultimate aim of defining the role of APOL1 risk variants in the long-term outcomes of kidney transplantation and living kidney donation.