APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors

• Authors: Barry I. Freedman, Wake Forest School of Medicine; Stephen Pastan, Emory University; Ajay K. Israni, University of Minnesota; David Schladt, Minneapolis Medical Research Foundation Inc; Bruce A. Julian, University of Alabama Birmingham; Michael D. Gautreaux, Wake Forest School of Medicine; Vera Hauptfeld, University of Alabama Birmingham; Robert Bray, Emory University; Howard Gebel, Emory University; Allan D Kirk, Emory University; Robert S. Gaston, Emory University School of Medicine; Jeffrey Rogers, Wake Forest School of Medicine; Alan C. Farney, Wake Forest School of Medicine; Giuseppe Orlando, Wake Forest School of Medicine; Robert J. Stratta, Wake Forest School of Medicine; Sumit Mohan, Columbia Univ Coll Phys & Surg; Lijun Ma, Wake Forest School of Medicine; Carl D. Langefeld, Wake Forest School of Medicine; Donald W. Bowden, Wake Forest School of Medicine; Pamela J. Hicks, Wake Forest School of Medicine; Nicholette D. Palmer, Wake Forest School of Medicine; Amudha Palanisamy, Wake Forest School of Medicine; Amber M. Reeves-Daniel, Wake Forest School of Medicine; W. Mark Brown, Wake Forest School of Medicine; Jasmin Divers, Wake Forest School of Medicine
• Journal Title: Transplantation
• Volume: Volume 100, Number 1
• Publisher: Lippincott, Williams & Wilkins | 2016-01-01, Pages 194-202
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/TP.0000000000000969
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Pathology; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Surgery; Transplantation; NONDIABETIC NEPHROPATHY; ALLOGRAFT SURVIVAL; UNITED-STATES; ORGAN DONORS; GENE-GENE; RECIPIENTS; VARIANTS; ASSOCIATION; DISEASE; RISK

Abstract

Background. Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. Methods. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLAmatch, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Results. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 - 10-4), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Conclusions. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.