Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure

B. I. Freedman*, B. A. Julian, S. O. Pastan, A. K. Israni, D. Schladt, M. D. Gautreaux, V. Hauptfeld, R. A. Bray, H. M. Gebel, A. D. Kirk, R. S. Gaston, J. Rogers, A. C. Farney, G. Orlando, R. J. Stratta, S. Mohan, L. Ma, C. D. Langefeld, P. J. Hicks, N. D. PalmerP. L. Adams, A. Palanisamy, A. M. Reeves-Daniel, J. Divers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

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.

Original languageEnglish
Pages (from-to)1615-1622
Number of pages8
JournalAmerican Journal of Transplantation
Volume15
Issue number6
DOIs
StatePublished - 1 Jun 2015
Externally publishedYes

Keywords

  • clinical research / practice
  • donors and donation: deceased
  • genetics
  • genetics
  • genomics
  • kidney disease
  • kidney transplantation / nephrology
  • molecular biology
  • molecular biology
  • translational research / science

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