Association of Tacrolimus Variability and Adherence in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Tacrolimus has a narrow therapeutic window and exhibits high intrapatient variability (IPV) in its pharmacokinetics. Kidney transplant recipients with high IPV in tacrolimus exposure are at increased risk of graft rejection and failure. One potential contributor to tacrolimus IPV is drug adherence. However, the relationship between tacrolimus IPV and drug adherence remains unclear. The aim of this study is to determine the association between tacrolimus IPV and adherence among stable kidney transplant recipients by performing systematic review and meta-analysis. PubMed, Embase, Cochrane, OpenGrey, Scopus, Clinicaltrial.gov, Web of Science, CINAHL, and medRxiv were searched from inception through October 23, 2024. The focus was on observational studies and randomized controlled trials comparing tacrolimus IPV in adherence and non-adherence groups. To account for differences between studies, we used a random-effects model to analyze tacrolimus IPV, with standardized mean difference (SMD) and a 95% confidence interval (95%CI). Four studies were included for meta-analysis. All of which are observational studies with a pooled sample size of 790, divided into 655 participants in adherence group and 135 participants in non-adherence group. The pooled estimate found a statistically significant difference of tacrolimus IPV between adherence and non-adherence group (SMD -0.24, 95% CI: -0.44, -0.04; p=0.017; I2=0.0%). Recent observational research indicates a relationship between variability in tacrolimus concentration and adherence among stable kidney transplant recipients. However, due to the quality concerns and their limited number of these studies, it is important to exercise caution in interpreting these results.