Clinical Impact of the Adaptation of Initial Tacrolimus Dosing to the CYP3A5 Genotype After Kidney Transplantation: Systematic Review and Meta-Analysis of Randomized Controlled Trials
- PMID: 33751414
- DOI: 10.1007/s40262-020-00955-2
Clinical Impact of the Adaptation of Initial Tacrolimus Dosing to the CYP3A5 Genotype After Kidney Transplantation: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abstract
Objective: The aim of this systematic review and meta-analysis was to compare the clinical outcomes between genotype-guided and conventional tacrolimus doses in kidney transplantation patients.
Materials and methods: We performed a comprehensive literature search of the PubMed, EMBASE, and Cochrane databases from the date of inception to 26 February 2020. References of the retrieved articles were also reviewed and any further relevant studies were included. The search terms included 'tacrolimus', 'cytochrome P-450 CYP3A', 'polymorphism, genetic', 'genomics', 'genome', 'genotype', 'genes', 'alleles', and 'pharmacogenetics'.
Results: Our study showed that the genotype-guided group included an increased proportion of patients with tacrolimus concentrations in the therapeutic range at steady state (risk ratio [RR] 1.40, 95% confidence interval [CI] 1.14-1.72, p = 0.001; high quality), with a trend for achieving therapeutic concentrations earlier compared with those in the conventional group. However, there was no statistical difference in the incidence of delayed graft function (RR 1.98, 95% CI 0.92-1.76, p = 0.12; moderate quality), incidence of acute rejection (RR 1.00, 95% CI 0.64-1.55, p = 1.00; moderate quality), incidence of graft survival censored for death (RR 1.02, 95% CI 0.98-1.06, p = 0.37; moderate quality), and incidence of adverse effects (AEs).
Conclusions: Although the genotype-guided group had a higher proportion of patients within the targeted concentration and less median time to achieve the therapeutic range, the clinical endpoints, including delayed graft function, acute rejection, graft survival censored for death, and AEs were similar in both groups. All in all, evidence suggested there was no utility in pharmacogenetics for tacrolimus based on the cytochrome P450 (CYP) 3A5 genotype. Studies with Chinese and African American populations are needed due to the frequency of genetic polymorphisms of CYP3A5. Furthermore, a dosing algorithm that includes demographic and clinical factors plus multiple genetic variants should be added for consideration, and may optimize early tacrolimus exposure.
References
-
- Thölking G, Gerth HU, Schuette-Nuetgen K, et al. Influence of tacrolimus metabolism rate on renal function after solid organ transplantation. World J Transplant. 2017;7(1):26–33. - DOI
-
- Muraki Y. Factors affecting the pharmacokinetics after living donor liver transplant. Yakugaku Zasshi. 2012;132(9):1011–7. - DOI
-
- Gonzalez D, Rao GG, Bailey SC, et al. Precision dosing: public health need, proposed framework, and anticipated impact. Clin Transl Sci. 2017;10(6):443–54. - DOI
-
- Ferraris JR, Argibay PF, Costa L, et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids. Pediatr Transplant. 2011;15(5):525–32. - DOI
-
- Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98(1):19–24. - DOI
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical