Kidney Transplant Outcomes and APOL1

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PROJECT SUMMARY Chronic kidney disease (CKD) affects >10% of the adult US population, costs tens of billions of dollars annually, and can lead to progressive kidney failure leading to need for renal replacement therapy. Successful kidney transplant reverses many of the chronic abnormalities in 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. We have established a multidisciplinary investigative team and outline plans for a multicenter transplant prospective recruiting clinical center for the RFA-DK-16-025 – “APOL1 Long- term Kidney Transplantation Outcomes Network (APOLLO) Clinical Centers”, to assess the outcome of kidney transplant recipients and living donors in relation to the African-ancestry APOL1 alleles. APOL1 risk alleles have been shown to explain a large part of the increased risk of African Americans compared to non-African American for end-stage renal 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. We propose to assess if the presence of APOL1 donor risk alleles is associated with kidney transplant outcomes (rate of change of kidney function, rates of acute rejection and graft failure defined as re- transplantation, initiation of dialysis or GFR < 15 ml/min/1.73m2) (Aim 1); to determine if acute rejection, viral infections and other genetic factors in the donor-recipient pair alters the impact of donor APOL1 risk alleles with kidney transplant outcomes (Aim 2); and determine the impact of kidney donation in African American donors with APOL1 risk alleles with up to 3.5 years of longitudinal follow-up (Aim 3). We are committed to collaborative protocol development, sharing best practices, and team science to achieve the APOLLO's objectives. The APOLLO network will also establish 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.