APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors

Transplantation. 2016 Jan;100(1):194-202. doi: 10.1097/TP.0000000000000969.

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, HLA match, 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), 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • African Americans / genetics*
  • Age Factors
  • Allografts
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Biomarkers / blood
  • Chi-Square Distribution
  • Creatinine / blood
  • Female
  • Genotype
  • Graft Survival / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Lipoproteins, HDL / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Phenotype
  • Proportional Hazards Models
  • Registries
  • Risk Factors
  • Time Factors
  • Tissue Donors*
  • Tissue and Organ Procurement
  • Treatment Outcome
  • United States / epidemiology
  • Young Adult

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Biomarkers
  • Lipoproteins, HDL
  • Creatinine