title: The APOL1 gene and allograft survival after kidney transplantation.
abstract: Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.
authors.affiliation: Department of Internal Medicine, Section on Nephrology, Winston-Salem, North Carolina, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Reeves-Daniel
authors.forename: J A
authors.initials: JA
authors.lastname: DePalma
authors.forename: A J
authors.initials: AJ
authors.lastname: Bleyer
authors.forename: M V
authors.initials: MV
authors.lastname: Rocco
authors.forename: M
authors.initials: M
authors.lastname: Murea
authors.forename: P L
authors.initials: PL
authors.lastname: Adams
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: D W
authors.initials: DW
authors.lastname: Bowden
authors.forename: P J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: R J
authors.initials: RJ
authors.lastname: Stratta
authors.forename: J-J
authors.initials: JJ
authors.lastname: Lin
authors.forename: D F
authors.initials: DF
authors.lastname: Kiger
authors.forename: M D
authors.initials: MD
authors.lastname: Gautreaux
authors.forename: J
authors.initials: J
authors.lastname: Divers
authors.forename: B I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D000328:Adult; D001741:Black or African American; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000208:ethnology* / Q000628:therapy*; D012306:Risk; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D008075:Lipoproteins, HDL