title: Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.
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.
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC.|Center for Human Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors: B I
authors: BI
authors: Freedman
authors: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors: B A
authors: BA
authors: Julian
authors: Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors: S O
authors: SO
authors: Pastan
authors: Division of Nephrology, Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN.|Minneapolis Medical Research Foundation, Minneapolis, MN.
authors: A K
authors: AK
authors: Israni
authors: Minneapolis Medical Research Foundation, Minneapolis, MN.
authors: D
authors: D
authors: Schladt
authors: General Surgery & HLA Immunogenetics Lab, Wake Forest School of Medicine, Winston-Salem, NC.
authors: M D
authors: MD
authors: Gautreaux
authors: Alabama Regional Histocompatibility Laboratory at UAB, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors: V
authors: V
authors: Hauptfeld
authors: Department of Pathology & Lab Medicine, Emory School of Medicine, Atlanta, GA.
authors: R A
authors: RA
authors: Bray
authors: Department of Pathology & Lab Medicine, Emory School of Medicine, Atlanta, GA.
authors: H M
authors: HM
authors: Gebel
authors: Department of Surgery, Duke University School of Medicine, Durham, NC.
authors: A D
authors: AD
authors: Kirk
authors: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors: R S
authors: RS
authors: Gaston
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors: J
authors: J
authors: Rogers
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors: A C
authors: AC
authors: Farney
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors: G
authors: G
authors: Orlando
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors: R J
authors: RJ
authors: Stratta
authors: Division of Nephrology, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY.
authors: S
authors: S
authors: Mohan
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC.
authors: L
authors: L
authors: Ma
authors: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors: C D
authors: CD
authors: Langefeld
authors: Center for Human Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors: P J
authors: PJ
authors: Hicks
authors: Center for Human Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors: N D
authors: ND
authors: Palmer
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC.
authors: P L
authors: PL
authors: Adams
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC.
authors: A
authors: A
authors: Palanisamy
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC.
authors: A M
authors: AM
authors: Reeves-Daniel
authors: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors: J
authors: J
authors: Divers
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000407:Alabama; D064591:Allografts; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006084:Graft Rejection / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007674:Kidney Diseases / Q000401:mortality / Q000601:surgery*; D016030:Kidney Transplantation / Q000401:mortality; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009657:North Carolina; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: clinical research / practice; donors and donation: deceased; genetics; genomics; kidney disease; kidney transplantation / nephrology; molecular biology; translational research / science