Influence of cytochrome P450 3A5 polymorphisms on viral infection incidence in kidney transplant patients treated with tacrolimus.

OBJECTIVE

The aim of this retrospective study was to determine the risk of viral infection in tacrolimus-treated kidney transplant patients.

METHODS

We analyzed kidney transplant recipients from 2002 to 2012, reporting all episodes of viral infection. All patients received induction with basiliximab followed by a standard regimen with tacrolimus, steroids, and antimetabolites. Genotypes of cytochrome P450 (CYP) 3A5 were determined with the use of the polymerase chain reaction method.

RESULTS

Fifty-one patients (17 women, 34 men; mean age, 41.6 ± 65.7 years) underwent kidney transplantation with tacrolimus-based immunosuppressive therapy. Thirty patients were diagnosed with 34 viral infections, including herpes simplex, adenovirus, mumps, varicella, and cytomegalovirus (CMV). CMV was the most common viral infection. In multivariate analysis, the CYP3A5 1 allele (P = .049) and negative serology for CMV (P = .018) were factors independently associated with the incidence of viral infection. After excluding CMV infection in CMV-seropositive donor/CMV-seronegative (D+R-) recipients in the analysis, the presence of the CYP3A5 1 allele was found to be an independent risk factor for viral infection. Recipients with the CYP3A5 3/3 genotype (nonexpressors) showed significantly higher dose-adjusted tacrolimus trough concentrations than patients with the CYP3A5 1 allele (expressors; respectively, 104.6 ± 65.6 vs 52.6 ± 62.3 ng/mL per mg/kg/d).

CONCLUSIONS

The CYP3A5 1 allele is associated with viral infection, possibly as a result of higher peak concentrations of tacrolimus. Further analyses, such as area under the concentration-time curve (AUC) for tacrolimus and polymorphisms of drug metabolism enzymes such as CYP3A4 are required to evaluate the influence of CYP3A5 on viral infection in kidney transplantation.