Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients

Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism. The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12h (C12) measured by CLIA were compared with that by LC–MS/MS using Bland–Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots. No significant difference was observed in tacrolimus C12 between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C12 of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C12 ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C12 measured by CLIA was 35% higher than that by LC–MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C12 of less than 3μg/l and CYP3A5*1/*3 genotype. This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels. ► We evaluated the cross-reactivity in tacrolimus CLIA in kidney transplantation. ► CYP3A5*3 affected the metabolic pathway of tacrolimus and its blood level. ► Blood tacrolimus level measured by CLIA was 35% higher than that by LC–MS/MS. ► A higher cross-reactivity was found in patients with a tacrolimus level of