NDT Advance Access published online on October 12, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp530
Black renal transplant recipients have poorer long-term graft survival than CYP3A5 expressers from other ethnic groups
1 Cellular and Molecular Medicine, Renal Medicine, St. George's, University of London, Cranmer Terrace, SW17 0RE 2 Department of Renal Medicine and Transplantation, St. George's Hospital, Blackshaw Road, SW17 0QT 3 Cardiac and Vascular Sciences, Analytical Unit, St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
Correspondence and offprint requests to: Iain A. M. MacPhee; E-mail: imacphee{at}sgul.ac.uk
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Abstract |
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Background. African American transplant recipients have poorer long-term outcomes than Caucasian Americans. This difference was not found in French patients, suggesting socialized medicine overcame this disparity. It has also been hypothesized that the difference relates to the higher prevalence of Black individuals who express the metabolic enzyme cytochrome P4503A5 (CYP3A5), with consequent altered handling of immunosuppressive drugs.
Methods. Records of 555 (50 Black; 505 non-Black) sequential renal transplant recipients from a single UK centre were analysed.
Results. Outcomes were significantly worse for Black patients: death-censored graft survival (5-year 66% versus 87%, P = 0.001); halving of year one estimated glomerular filtration rate (mean 8.8 versus 10.8 years, P = 0.008); first-year graft loss (12% versus 3.8%, P = 0.02); and death-censored graft survival in patients surviving the first year with functioning grafts (5-year 77% versus 94%, P = 0.02). Death-censored 5-year graft survival was poorer in Black CYP3A5 expressers than in non-Black CYP3A5 expressers (62% versus 93%, P = 0.002). Following multivariate analysis, the Black group demonstrated poorer graft survival as compared to the non-Black group (hazard ratio 0.46, 95% CI 0.25–0.85, P = 0.002). In a subgroup of genotyped transplant recipients, ethnicity (hazard ratio 0.31, 95% CI 0.15–0.64, P = 0.002), and not CYP3A5 expresser status, persists as an independent risk factor for graft survival following multivariate analysis.
Conclusion. In this cohort of patients with socialized medicine, Black recipients had poorer long-term outcomes than individuals from other ethnic groups. This was independent of CYP3A5 expresser status.
Keywords: CYP3A5; ethnicity; pharmacogenetics; renal transplantation; tacrolimus
Received for publication: 23. 7.09
Accepted in revised form: 15. 9.09