title: Effect of Replacing Race With Apolipoprotein L1 Genotype in Calculation of Kidney Donor Risk Index.
abstract: Renal allografts from deceased African American donors with two apolipoprotein L1 gene (APOL1) renal-risk variants fail sooner than kidneys from donors with fewer variants. The Kidney Donor Risk Index (KDRI) was developed to evaluate organ offers by predicting allograft longevity and includes African American race as a risk factor. Substituting APOL1 genotype for race may refine the KDRI. For 622 deceased African American kidney donors, we applied a 10-fold cross-validation approach to estimate contribution of APOL1 variants to a revised KDRI. Cross-validation was repeated 10 000 times to generate distribution of effect size associated with APOL1 genotype. Average effect size was used to derive the revised KDRI weighting. Mean current-KDRI score for all donors was 1.4930 versus mean revised-KDRI score 1.2518 for 529 donors with no or one variant and 1.8527 for 93 donors with two variants. Original and revised KDRIs had comparable survival prediction errors after transplantation, but the spread in Kidney Donor Profile Index based on presence or absence of two APOL1 variants was 37 percentage points. Replacing donor race with APOL1 genotype in KDRI better defines risk associated with kidneys transplanted from deceased African American donors, substantially improves KDRI score for 85-90% of kidneys offered, and enhances the link between donor quality and recipient need.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: B A
authors.initials: BA
authors.lastname: Julian
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: R S
authors.initials: RS
authors.lastname: Gaston
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: W M
authors.initials: WM
authors.lastname: Brown
authors.affiliation: Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: A M
authors.initials: AM
authors.lastname: Reeves-Daniel
authors.affiliation: Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN.|Minneapolis Medical Research Foundation, Minneapolis, MN.
authors.forename: A K
authors.initials: AK
authors.lastname: Israni
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN.
authors.forename: D P
authors.initials: DP
authors.lastname: Schladt
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: S O
authors.initials: SO
authors.lastname: Pastan
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, New York, NY.
authors.forename: S
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC.|Center for Human Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: B I
authors.initials: BI
authors.lastname: Freedman
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.|Center for Human Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: J
authors.initials: J
authors.lastname: Divers
mesh_terms: D000293:Adolescent; D000328:Adult; D000075944:Apolipoprotein L1 / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics / Q000401:mortality*; D006085:Graft Survival; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044469:Racial Groups / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D015415:Biomarkers
keywords: clinical research/practice; disparities; donors and donation: deceased; genetics; kidney transplantation/nephrology; organ allocation; organ procurement and allocation