Title :

Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study

Author(s) :

Lenain, Rémi [Auteur]
Service de Néphrologie et Transplantation rénale [CHRU-lille]
Maanaoui, Mehdi [Auteur]
Service de Néphrologie et Transplantation rénale [CHRU-lille]
Hamroun, Aghilès [Auteur]
Service de Néphrologie et Transplantation rénale [CHRU-lille]
Larrue, Romain [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Van Der Hauwaert, Cynthia [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Gibier, Jean-Baptiste [Auteur]
Service de pathologie [CHU Lille]
Gnemmi, Viviane [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Gomis, Sébastien [Auteur]
Service de Néphrologie et Transplantation rénale [CHRU-lille]
Labalette, Myriam [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Broly, Franck [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Hennart, Benjamin [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Pottier, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Hazzan, Marc [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Cauffiez, Christelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Glowacki, François [Auteur]
Service de Néphrologie et Transplantation rénale [CHRU-lille]

Journal title :

Journal of personalized medicine

Pages :

1002

Publisher :

MDPI

Publication date :

2021-10-02

ISSN :

2075-4426

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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. ...
Show more >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.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (MSAP) - USR 3290

Source :

Harvested from HAL