4/14 APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

NIH RePORTER · NIH · U01 · $310,000 · view on reporter.nih.gov ↗

Abstract

Abstract Kidneys from deceased African American donors have reduced allograft survival compared to kidneys from donors from European Americans. Likewise, kidneys from deceased donors with 2 apolipoprotein L1 gene (APOL1) renal-risk variants, defined as APOL1 high-risk genotypes, have shorter allograft survival. Importantly, many kidneys transplanted from deceased donors with 2 APOL1 risk variants do not fail rapidly. We postulate that APOL1 interacts with other environmental or inherited factors to accelerate the failure of kidneys transplanted from deceased donors. APOL1 renal-risk variants are almost exclusively in individuals of recent African ancestry. Relative differences in the prevalence of blood types and human leukocyte antigens lead to more kidneys from deceased African American donors being allocated to African Americans, potentially exacerbating disparities in transplant outcomes. African American living kidney donors face a greater risk of post-donation kidney failure compared to White living donors, but including APOL1 genotyping in the evaluation and selection of African American donors remains controversial. The National Institutes of Health established the “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) Consortium in 2017 to prospectively address several critical questions regarding the broad implementation of APOL1 genotyping in kidney transplantation and to assess its role in the evaluation of living donors. APOLLO assesses factors determining time to allograft failure (primary outcome), post-transplant kidney function and proteinuria (secondary outcomes) in kidneys from donors with recent African ancestry. The APOLLO Consortium includes a Scientific and Data Research Center (SDRC) and 13 Clinical Centers, including our Center with 8 kidney transplant programs, encompassing high-volume and smaller programs with diverse practice patterns and geographic representation. Through 9/29/22, APOLLO, in its initial phase, has prospectively collected DNA from 3604 deceased donors and is following outcomes for the 4890 recipients. APOLLO has collected DNA from 2436 recipients of whom Clinical Center 04 (CC04) has enrolled 17.1% (417). CC04 also recruited 7% (15) of the APOLLO living donors and their recipients. In the proposed APOLLO Phase 2 study, we will prospectively collect long-term follow-up data and measure urine albumin to creatinine ratio > 2 years after transplantation for all APOLLO Phase 1 participants. For those at the University of Alabama at Birmingham, we will provide detailed clinical data, collect biospecimens (blood and urine after 1st post-transplant year), and collect slides from all allograft biopsies for APOLLO Digital Pathology Repository. Working with the SDRC, CC04 will return APOL1 genotype results to recipients and living donors at our aligned transplant programs. The results from this national study have the potential to transform organ allocation and informed-consent processes for the transplantati...

Key facts

NIH application ID
10917274
Project number
5U01DK115997-07
Recipient
UNIVERSITY OF ALABAMA AT BIRMINGHAM
Principal Investigator
Gaurav Agarwal
Activity code
U01
Funding institute
NIH
Fiscal year
2024
Award amount
$310,000
Award type
5
Project period
2017-09-25 → 2028-05-31