APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale

Abstract

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.

COVID-19–Associated Glomerular Disease

“…Current models of APOL1-induced nephrotoxicity suggest that intrinsic renal expression is important for nephrotoxicity and specifically, for podocyte injury. 27,30,31 Patient 2 showed discordance between recipient and transplant kidney APOL1 genotype. The patient (recipient) carried the high-risk APOL1 genotype, whereas the donor graft carried low-risk genotype G1/G0.…”

Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical Practice

“…Donor candidates can be informed that having two APOL1 allele risk variants increases the lifetime risk of kidney failure but that the precise kidney failure risk for an affected individual after donation cannot currently be quantified. The guideline also emphasizes the need for ongoing research to define the role of APOL1 genotyping in the living donor candidate evaluation, a topic being addressed in new initiatives like the National Institutes of Health-sponsored APOL1-Long Term Outcomes study and the Living Donor Extended Time Outcomes study (13).…”

Donor Family History of ESKD and Long-term Outcomes Among African American Living Kidney Donors: A Retrospective Cohort Study

“…Our current knowledge of impact of APOL1 variants on post-donation kidney function is limited (13) and therefore APOL1 testing is not routinely used for donor selection. The NIH initiated prospective study encompassing all live African American kidney donors in United States, APOL1 Long-term Kidney Transplantation Outcomes Network(APOLLO), is designed to address some of these issues (14). Until results of such studies are available, family history remains an important tool in donor selection.…”