39Renal Electrolyte and Hypertension Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA; 40Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; 41Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland, USA; and 42Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)–sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. Methods: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. Results: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. Conclusion: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation. Kidney Int Rep (2020) 5, 278–288; https://doi.org/10.1016/j.ekir.2019.11.022 KEYWORDS: African Americans; APOL1; chronic kidney disease; graft failure; kidney transplantation; outcomes ª 2019 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). I mplementation of a new Kidney Allocation System in 2014 was an attempt to remedy the shortage of kidneys for transplantation and premature loss of functioning allografts caused by recipient death from nonrenal causes.1,2 The new Kidney Allocation System attempts to increase renal allograft survival by better matching recipients with quality of donor kidneys. The Kidney Allocation System also improves equity for highly sensitized patients and those with longer dialysis vintage. An essential aspect of the new Kidney Allocation System is the Kidney Donor Risk Index (KDRI), a scoring system based on 10 deceased-donor factors that objectively determines the quality of kidneys and estimates graft life span. African American ethnicity/race is an important characteristic considered in the KDRI because it projects an approximate 20% higher risk for allograft loss. The KDRI was designed before widespread recognition of the role of apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants (RRVs) on susceptibility to ESKD in populations with recent African ancestry.3,4 These populations have similar genetic composition to individuals currently residing in Africa. APOL1 RRVs are present nearly exclusively in individuals with recent African ancestry and cause a range of kidney diseases in an autosomal recessive inheritance pattern.5 A minority of individuals with APOL1 high-risk genotypes (2 RRVs; G1G1, G2G2, or G1G2) develop nephropathy.5 Retrospective studies support that variation in donor APOL1 genotypes, not donor African American ancestry per se, increases the risk for shorter renal allograft survival.6–9 Donor high-risk APOL1 genotypes are also associated with kidney disease in living-kidney donors.10 To improve safety in living-kidney donation and outcomes for kidney transplant recipients, as well as increase knowledge of APOL1 effects after transplantation, the National Institute of Diabetes and Digestive and Kidney Diseases issued a request for applications entitled the APOLLO in November 2016.11 The National Institute on Minority Health and Health Disparities and the National Institute of Allergy and Infectious Diseases provide cofunding and research expertise. This U01 Consortium supports a Scientific and See Commentary on Page 252 BI Freedman et al.: APOLLO Study Design and Rationale CLINICAL RESEARCH Kidney International Reports (2020) 5, 278–288 279 Data Research Center (SDRC or Coordinating Center) including a cIRB and Clinical Laboratory Improvement Amendments–approved genotyping laboratory. APOLLO supports 13 Clinical Centers