Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies

Autores de IIS La Fe

• Luis Esteban Rojas Orellana

  Autor

• María José Herrero Cervera

  Autor

• Virginia Bosó Ribelles

  Autor

• Juan Pablo Reig Mezquida

  Autor

• José Luis Poveda Andrés

  Autor

• Juan Eduardo Megías Vericat

  Autor

• Sergio Bea Granell

  Autor

• Salvador F Aliño Pellicer

  Autor

Participantes ajenos a IIS La Fe

• Neumann I

Grupos

• Farmacogenética

Abstract

The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expresser genotype might have higher risk of acute rejection and chronic nephrotoxicity. In conclusion, CYP3A5 6986A>G polymorphism can affect tacrolimus pharmacokinetics and the incidence of acute rejection and chronic nephrotoxicity on kidney transplant recipients. Patients at high risk of developing tacrolimus-related complications could be detected even before their kidney transplant.

Keywords

• CYP3A5 GENETIC-POLYMORPHISM; SINGLE-NUCLEOTIDE POLYMORPHISMS; RENAL-ALLOGRAFT RECIPIENTS; ACUTE REJECTION; CALCINEURIN INHIBITORS; TROUGH CONCENTRATIONS; DOSE REQUIREMENTS; ABCB1 POLYMORPHISMS; CYTOCHROME-P450 3A; IMPACT