PROJECT SUMMARY We submit this proposal titled “Living donor Extended Time Outcomes (LETO)” as an ancillary study to the newly initiated “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) Network. The APOLLO Consortium represents the most ambitious national study addressing the implications of donor apolipoprotein L1 gene (APOL1) renal-risk variants on kidney transplant outcomes. However, the prospective design of the parent APOLLO is underpowered to assess postdonation kidney health in living donors and outcomes in recipients of their kidneys due to due to short follow-up duration and secular trends resulting in diminishing numbers of persons with 2 APOL1 renal-risk variants donating in recent calendar years. We propose a cost-effective “hybrid” study design—jointly analyzing data collected at home-based research visits together with data collected as part of clinical care (as entered into a national registry)—that will greatly increase the number of person-years of follow-up and enhance study power. We will enroll 1,100 living donors who donated from 2001-2005 to generate data that will have a major impact on the clinical practice of living kidney donation in African Americans. Our specific aims are: Aim 1: To determine in a nationally representative sample whether African American living kidney donors with 2 APOL1 renal-risk variants are at higher risk of developing clinically significant chronic kidney disease (estimated glomerular filtration rate <45 ml/min/1.73m2) approximately two decades after donation. Aim 2: To determine whether other independent (or APOL1 interactive) gene variants associate with increased risk of clinically significant chronic kidney disease (estimated glomerular filtration rate <45 ml/min/1.73m2) in African American living kidney donors. Aim 3: To determine the impact of donor APOL1 renal-risk variants and other novel genetic risk factors on graft survival and recipient outcomes in a nationally representative sample of living donor kidney transplant recipients from African American living donors.