H- 10: Criteria for living donor transplantation
C- 01: Focal and segmental hyalinosis
Apolipoprotein L1 Gene Variants in Deceased Organ Donors Are
Associated With Renal Allograft Failure
B. I. Freedman1,2,*, B. A. Julian3, S. O. Pastan4, A. K. Israni5,6, et al.
Journal : American Journal of Transplantation
Year : 2015 / Month : June
Volume : 15
Pages : 1615–1622
Keywords: translational research / science; clinical research / practice; genetics; kidney
transplantation / nephrology; molecular biology; donors and donation: deceased; genetics; kidney
disease; molecular biology; genomics
ABSTRACT
Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors
were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2
variants were genotyped in newly accrued DNA samples from African American deceased donors of
kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft
outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and
race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor
type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward
shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR]
2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR
2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with
allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy
variants reproducibly associate with higher risk for allograft failure after transplantation. These findings
warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk
variants at organ recovery and incorporation of results into allocation and informed-consent processes.
COMMENTS
Variants of the apolipoprotein L1 (APOL1) gene have been linked to a variety of renal diseases
including focal segmental glomerulosclerosis and hypertension-attributed nephropathy Such genetic
variants have been first described in patients with African ancestry, but have also been observed in the
white population to a lesser degree. Two common coding variants in the APOL1gene (G1 and G2),
known to impact resistance to Trypanosoma infections, appear to confer most of the renal-associated
risk. Patients with two copies of the coding variants are at highest risk while those with one allele have
similar risk to patients with zero alleles.
Recipients who received a donor kidney with two APOL1 alleles had over a twofold increased risk of
graft failure (HR 2.26; 95% CI 1.37–3.74; p = 0.001). Despite a larger sample (n = 221), two APOL1
alleles was not independently associated with graft loss in recipients of Alabama donor kidneys (HR
2.71; 95% CI 0.95–7.69) while it was in the original cohort of 127 patients from North Carolina (HR
2.33; 95% CI 1.10–4.90). Examination of the survival curves reveals that most grafts failed within the
first 2 years posttransplantation, although APOL1 risk variants were not associated with delayed graft
function or acute rejection.
The retrospective analysis by Freedman et al has not produced evidence to support the use of APOL1
genotyping in deceased donor transplantation.
Pr. Jacques CHANARD
Professor of Nephrology