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Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.

ABSTRACT: Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 European American (EA) deceased donors based on 38 single-nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1, including previously associated index and haplotype-tagging SNPs. Tests for association with time to allograft failure were performed for the 1233 resultant kidney transplantations, adjusting for recipient age, sex, ethnicity, cold ischemia time, panel reactive antibody, human leukocyte antigen match, expanded-criteria donation, and APOL1-nephropathy variants in AA donors. Interaction analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of all transplantations, ABCB1 index SNP rs1045642 was associated with time to allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1 SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors. Interactions between ABCB1 and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from AA donors.

SUBMITTER: Ma J

PROVIDER: S-EPMC4556550 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.

Ma Jun J Divers Jasmin J Palmer Nicholette D ND Julian Bruce A BA Israni Ajay K AK Schladt David D Pastan Stephen O SO Chattrabhuti Kryt K Gautreaux Michael D MD Hauptfeld Vera V Bray Robert A RA Kirk Allan D AD Brown W Mark WM Gaston Robert S RS Rogers Jeffrey J Farney Alan C AC Orlando Giuseppe G Stratta Robert J RJ Guan Meijian M Palanisamy Amudha A Reeves-Daniel Amber M AM Bowden Donald W DW Langefeld Carl D CD Hicks Pamela J PJ Ma Lijun L Freedman Barry I BI

Kidney international 20150408 3

Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 European American (EA) deceased donors based on 38 single-nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1, including previously associated index and haplotype-tagging SNPs. Tests for association with time to allograft ...[more]

PMID: 25853335

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Project description:Background and objectivesUse of diabetic donor kidneys has been a necessary response to the donor organ shortage. Recipients of diabetic donor kidneys have higher mortality risk compared with recipients of nondiabetic donor kidneys. However, the survival benefit of transplantation with diabetic donor kidneys over remaining on the waitlist has not been previously evaluated.Design, setting, participants, & measurementsWe performed an observational cohort study of 437,619 kidney transplant candidates from the Organ Procurement and Transplantation Network database, including 8101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. We used time-varying Cox proportional hazards modeling to assess the mortality risk of accepting a diabetic donor kidney compared with remaining on the waitlist or receiving a nondiabetic donor kidney.ResultsAmong transplant recipients, median follow-up was 8.9 years and mortality rate was 35 deaths per 1000 person-years. Recipients of diabetic donor kidneys had 9% lower mortality compared with remaining on the waitlist or transplantation with a nondiabetic donor kidney (adjusted hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.98). Although recipients of nondiabetic donor kidneys with a Kidney Donor Profile Index score >85% had lower mortality risk (adjusted hazard ratio, 0.86; 95% confidence interval, 0.81 to 0.91), recipients of diabetic donor kidneys with an index score >85% did not show any difference (adjusted hazard ratio, 1.09; 95% confidence interval, 0.97 to 1.22). Patients aged <40 years attained no survival benefit from transplantation with diabetic donor kidneys; diabetic patients at centers with long waitlist times attained the greatest survival benefit.ConclusionsDiabetic donor kidneys appear associated with higher mortality risk compared with nondiabetic donor kidneys, but offer greater survival benefit compared with remaining on the waitlist for many candidates. Patients with high risk of mortality on the waitlist at centers with long wait times appear to benefit most from transplantation with diabetic donor kidneys.

Dataset Information

Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.

Publications

Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.

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