Abstract: SA-PO019
Impact of CYP3A5 Polymorphism on Clinical Outcome After Renal Transplantation
Session Information
- Transplantation: Clinical Outcomes
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1802 Transplantation: Clinical
Authors
- Lenain, Remi, CHRU Lille, Lille, France
- Hamroun, Aghiles, CHRU Lille, Lille, France
- Maanaoui, Mehdi, CHRU Lille, Lille, France
- Van der hauwaert, Cynthia, EA 4483 Faculté de Médecine de Lille, Lille, France
- Broly, Franck, Centre de Biologie Pathologie Génétique, Lille, France
- Labalette, Myriam, CHRU Lille, Lille, France
- Pottier, Nicolas, University of lille, Lille, France
- Cauffiez, Christelle, EA4483, Lille, France
- Glowacki, Francois, CHRU Lille, Lille, France
Background
Tacrolimus exhibits pharmacokinetics variability partly explained by CYP3A5 activity. In contrast to *3/*3 genotype, those carrying at least one CYP3A5*1 allele exhibit higher enzyme activity leading to lower Tac through blood level despite higher daily dose. In this study, we aimed to evaluate the impact of CYP3A5 polymorphism on renal graft outcome
Methods
This monocentric cohort includes 1252 renal transplant recipients with a mean follow up (FU) of 4 years (up to 12.1y). Genotyping of the 6986A>G allelic variant corresponding to CYP3A5*3 was systematically performed. After 3-months post-transplant, Tac through blood level target range was 5-7ng/ml. However in order to avoid Tac-induced nephrotoxicity, Tac daily dose was limited to a maximum of 0.1 mg/kg/day irrespective of CYP3A5 genotype
Results
Our sample includes 224 CYP3A5*1/- patients (13.9%) including 35 *1/*1 genotype recipients. During the FU, we observed 221 graft losses or deaths (17.65%). At baseline, there was no significant difference in characteristics between *3/*3 and *1/- groups. Despite higher daily dose, *1/- recipients exhibit systematically significant lower Tac through blood level during the FU (p<0.01). Multivariate analysis doesn't show any significant influence of *1/- genotype (HR=0.73, CI95% 0.48–1.09, p=0.12) on patient-graft survival. However, GFR decline was significantly lower for the *1/- group (p=0.004). At five years, eGFR was significantly better for *1/- recipients (47 vs 42 mL/min/1.73m2, p<0.001). CYP3A5 genotype doesn't impact the risk of rejection (HR for *1/- group=0.96, CI95% 0.66-1.42, p=0.87)
Conclusion
In this long-term study, CYP3A5*1/- recipients exhibited lower Tac through blood level with no impact on the rejection rate. Renal survival was independent of CYP3A5 genotype. However, the kidney graft function was significantly better in this subgroup showing a lower Tac-induced nephrotoxicity