1. Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study
- Author
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Rémi Lenain, Romain Larrue, François Glowacki, Christelle Cauffiez, Franck Broly, Viviane Gnemmi, Aghilès Hamroun, Myriam Labalette, Mehdi Maanaoui, Cynthia Van der Hauwaert, Nicolas Pottier, Jean-Baptiste Gibier, Benjamin Hennart, Marc Hazzan, Sebastien Gomis, Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lille Inflammation Research International Center - U 995 (LIRIC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, and IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
- Subjects
medicine.medical_specialty ,therapeutic drug monitoring ,[SDV]Life Sciences [q-bio] ,Urology ,Medicine (miscellaneous) ,Renal function ,chemical and pharmacologic phenomena ,Article ,polymorphism ,Pharmacokinetics ,medicine ,tacrolimus ,pharmacogenetics ,integumentary system ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,food and beverages ,Retrospective cohort study ,renal transplantation ,Tacrolimus ,Transplantation ,surgical procedures, operative ,Therapeutic drug monitoring ,Medicine ,business ,Pharmacogenetics - Abstract
The pharmacokinetic variability of tacrolimus can be partly explained by CYP3A5 activity. Our objective was to evaluate a tacrolimus sparing policy on renal graft outcome according to CYP3A5 6986A>, G genetic polymorphism. This retrospective study included 1114 recipients with a median follow-up of 6.3 years. Genotyping of the 6986A>, G allelic variant corresponding to CYP3A5*3 was systematically performed. One year after transplantation, tacrolimus blood trough concentration (C0) target range was 5–7 ng/mL. However, daily dose was capped to 0.10 mg/kg/day regardless of the CYP3A5 genotype. A total 208 CYP3A5*1/- patients were included. Despite a higher daily dose, CYP3A5*1/- recipients exhibited lower C0 during follow-up (p <, 0.01). Multivariate analysis did not show any significant influence of CYP3A5*1/- genotype (HR = 0.70, 0.46–1.07, p = 0.10) on patient-graft survival. Glomerular Filtration Rate (GFR) decline was significantly lower for the CYP3A5*1/- group (p = 0.02). The CYP3A5*1/- genotype did not significantly impact the risk of biopsy-proven acute rejection (BPAR) (HR = 1.01, 0.68–1.49, p = 0.97) despite significantly lower C0. Based on our experience, a strategy of tacrolimus capping is associated with a better GFR evolution in CYP3A5*1/- recipients without any significant increase of BPAR incidence. Our study raised some issues about specific therapeutic tacrolimus C0 targets for CYP3A5*1/- patients and suggests to set up randomized control studies in this specific population.
- Published
- 2021
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