13/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

We are applying to continue participating as an APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Study Clinical Center (CC). The NIH-funded APOLLO Study is performing a national prospective evaluation of deceased donor and recipient APOL1 risk variants in transplants from African American kidney donors to determine effects on outcomes. In addition, APOLLO studies APOL1 genotypes in African American living kidney donors for effects on their post-donation health. Kidney transplants from deceased African American donors typically do not function as long as those from European American deceased donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 (APOL1) gene risk variants in donors may contribute. The APOL1 risk variants are common in populations with recent African ancestry (such as African Americans), where they are strongly associated with end-stage kidney disease. In contrast, they are rare in other population groups. APOL1 genotype data may prove to be clinically useful in those with recent African ancestry in the setting of allocation of deceased donor kidneys for transplantation and assessment of prospective live kidney donors. Genotypic information may provide a more accurate assessment of the likelihood for long-term graft function in donor kidneys, thereby improving matching of donor kidneys with recipients to optimize graft and patient survival. Information may better inform physicians about organ quality prior to decisions on allocation. Information lacking from prior studies will be analyzed, including recipient APOL1 genotypes, kidney histology, viral infection (BK, CMV, SARS-CoV-2), donor specific antibodies, medications, cold ischemia time and acute rejection. Our investigative team, led by two PIs with complementary expertise, recruited the second largest number of eligible kidney transplant recipients in APOLLO to date. Before APOL1 genotyping can be clinically useful, a prospective national study was required to evaluate transplant outcomes from African American kidney donors and recipients of their kidneys based on their genotypes. This was the rationale and setting for the landmark APOLLO Study. Our CC has worked closely with the Wake Forest APOLLO Scientific and Data Research Center (SDRC) and the other participating CCs to recruit and prospectively follow eligible kidney donors and transplant recipients based on the APOLLO Protocol. In Phase 2, we will continue follow-up and measure urine albumin, as well as collect additional biosamples. APOLLO results have the potential to transform the organ allocation and informed consent processes in kidney transplantation, optimize renal allograft survival, reduce discard of good-quality kidneys, and protect the health of living kidney donors.