Association between tacrolimus intrapatient variability and clinical outcomes in kidney transplantation: a retrospective cohort study.

Background: In therapeutic drug monitoring (TDM) of tacrolimus, trough concentration is the most commonly used monitoring indicator, which has limited association with clinical outcomes. Intrapatient variability (IPV), as a novel monitoring marker for describing the extent of fluctuation in blood concentration, holds promise as an additional monitoring tool. The effect of tacrolimus IPV on Chinese kidney transplantation outcomes is unclear, and the aim of this study is to explore the association between IPV and poorer outcomes of Chinese kidney transplantation recipients and to discuss the influence of genotype. Methods: A total of 152 patients were enrolled, whose kidney transplantation operations were carried out from January 2015 to February 2022 in Peking University Third Hospital. IPV was calculated by coefficient of variation (CV) of tacrolimus whole blood concentrations during 6 and 12 months after transplantation. Clinical outcomes were analyzed between patients with high IPV and low IPV, including graft loss, acute rejection (AR), elevated serum creatinine (Scr), infection, hemogram abnormality and electrolyte disturbance. Moreover, the associations were compared according to different genotypes. Results: High IPV was associated with AR [hazard ratio (HR) =3.420; 95% confidence interval (CI): 1.142-10.245], hyperuricemia, and hypocalcemia (P<0.05). In cytochrome P450 (CYP)3A5 nonexpressers, high IPV was associated with graft loss, elevated Scr, hyperuricemia, hypocalcemia, hypomagnesemia and leukopenia (P<0.05), whereas no significant association was detected in CYP3A5 expressers (P>0.05). Conclusions: IPV is associated with clinical outcomes such as AR in Chinese kidney transplantation recipients. More attention should be paid to the association between high IPV and adverse outcomes in CYP3A5 nonexpresser recipients.