9/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

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PROJECT SUMMARY/ABSTRACT Successful kidney transplant reverses many of the chronic abnormalities in chronic kidney disease (CKD) and has shown to improve not only quality of life but also patient survival compared to renal replacement therapy. It is vital to identify strategies that improve and prolong organ function. APOL1 risk alleles have been shown to explain in part the increased risk of African Americans compared to non-African American for end-stage kidney disease. However, the association of APOL1 alleles with kidney transplant outcomes such as deterioration of kidney function, acute rejection, and allograft loss as well as living donor health is unclear. APOL1 genotyping has the potential to reduce the discard of good-quality kidneys from AA donors and increase the number of transplants overall. We are responding to RFA-DK-22-506 – “APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Centers”, to continue as a clinical center that builds upon the accomplishments of our established multidisciplinary research group in the first phase. As a successful recruitment site with our aligned 19 transplant programs, the proposal builds upon an established infrastructure and our experience recruiting APOLLO participants. In Phase 1 of APOLLO, we have successfully consented 156 kidney transplant recipients and 12 living donors, with DNA on hand in 151 recipients (97%) and 12 donors (100%), across these centers. We propose to collect long-term follow-up data on all APOLLO participants. (Aim 1); to provide detailed clinical data and biospecimens on APOLLO participants from our CC providing unique data not available in national registries: kidney biopsy results, acute rejection types and treatment, recurrent disease, changes in immunosuppression, medical compliance, bacterial and viral infections, proteinuria, creatinine and donor specific HLA antibodies, among others (Aim 2); and to facilitate return of APOL1 genotype results to participants (Aim 3). We are committed to collaborative protocol development, sharing best practices, and team science to achieve the APOLLO’s objectives. The APOLLO network has established a high-quality resource (data and specimen repository of blood, urine, DNA, and RNA) for future basic, clinical and translational research in transplantation. The proposed research plan will have future diagnostic, prognostic and therapeutic implications. In addition, it could have policy implications as kidneys may need to be allocated in the future taking into account the donor APOL1 genotype. The proposed research plan, by improving our understanding of the impact of APOL1 gene in kidney transplantation, has the potential to dramatically impact public health and diminish kidney discards for transplantation.