title: APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.
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.
authors.affiliation: 1 Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC. 2 Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC. 3 Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA. 4 Division of Nephrology, Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN. 5 Minneapolis Medical Research Foundation, Minneapolis, MN. 6 Division of Nephrology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL. 7 General Surgery and HLA Immunogenetics Laboratory, Wake Forest School of Medicine, Winston-Salem, NC. 8 Alabama Regional Histocompatibility Laboratory at UAB, University of Alabama at Birmingham School of Medicine, Birmingham, AL. 9 Department of Pathology and Laboratory Medicine; Emory School of Medicine, Atlanta, GA. 10 Department of Surgery, Duke University School of Medicine, Durham, NC. 11 Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC. 12 Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, New York, NY. 13 Division of Public Health Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Pastan
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Israni
authors.forename: David
authors.initials: D
authors.lastname: Schladt
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gautreaux
authors.forename: Vera
authors.initials: V
authors.lastname: Hauptfeld
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bray
authors.forename: Howard M
authors.initials: HM
authors.lastname: Gebel
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
authors.forename: Robert S
authors.initials: RS
authors.lastname: Gaston
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rogers
authors.forename: Alan C
authors.initials: AC
authors.lastname: Farney
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Orlando
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stratta
authors.forename: Sumit
authors.initials: S
authors.lastname: Mohan
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Amudha
authors.initials: A
authors.lastname: Palanisamy
authors.forename: Amber M
authors.initials: AM
authors.lastname: Reeves-Daniel
authors.forename: W Mark
authors.initials: WM
authors.lastname: Brown
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D064591:Allografts; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D009927:Tissue and Organ Procurement; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D015415:Biomarkers; D008075:Lipoproteins, HDL; D003404:Creatinine