Donor P-gp polymorphisms strongly influence renal function and graft loss in a cohort of renal transplant recipients on cyclosporine therapy in a long-term follow-up

Autor: Woillard, Jean-Baptiste, Rerolle, Jean-Philippe, Picard, Nicolas, Rousseau, Annick, Guillaudeau, A., Munteanu, Etienne, Essig, Marie, Drouet, M., Le Meur, Yann, Marquet, Pierre
Přispěvatelé: Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], Service d'Hématologie biologique [CHU Limoges], Service d'Immunologie et immunogénétique [CHU Limoges], Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Marquet, Pierre
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics, American Society for Clinical Pharmacology and Therapeutics, 2010, 88 (1), pp.95-100. ⟨10.1038/clpt.2010.62⟩
ISSN: 0009-9236
1532-6535
DOI: 10.1038/clpt.2010.62⟩
Popis: International audience; Cyclosporin A (CsA) is a substrate for cytochrome P450 3A and the efflux transporter P-glycoprotein (P-gp; ABCB1), both abundantly expressed in the kidney. In a long-term follow-up of a cohort of patients who had received kidney transplants between the years 1990 and 2005, we retrospectively investigated the effect of CYP3A4, CYP3A5, and ABCB1 polymorphisms in kidney graft donors on recipients' renal function and risk of subsequent graft loss. DNA samples from 227 donors and clinical data from the 259 respective recipients were analyzed. Graft loss was significantly associated with the presence of the ABCB1 variant haplotype 1236T/2677T/3435T in the donor (1236T/2677T/3435T vs. other haplotypes: hazard ratio = 9.346; 95% confidence interval (CI) (2.278-38.461); P = 0.0019) and with previous episodes of acute organ rejection (hazard ratio = 3.077; 95% CI (1.213-7.812); P = 0.0178). The variant haplotype was also associated with a greater decrease in renal function (homozygotes for TTT -3.047 mlxmin(-1)/year; heterozygotes for TTT -4.435 mlxmin(-1)/year; others -2.186 mlxmin(-1)/year; P = 0.0240). The study showed that the presence of ABCB1 polymorphisms in donors influences long-term graft outcome adversely with decrease in renal function and graft loss in transplant recipients receiving CsA.
Databáze: OpenAIRE
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