The Number of Episodes of Subtherapeutic Tacrolimus Blood Level Is Independently Associated With Reduced Kidney Graft Survival

Background: Tacrolimus blood level variability is associated with reduced graft survival among kidney transplant recipients. To date, no practical approach for reducing variability has been validated. We defined specific tacrolimus blood level patterns correlated with variability and evaluated their independent association with reduced graft survival. Methods: In this single-center retrospective study, we predefined 12 patterns that exhibited correlation with high tacrolimus blood level variability. Subsequently, we utilized a multivariate Cox proportional hazard model, in conjunction with the Akaike information criteria, to evaluate the association between the predefined patterns and decreased graft survival. Results: Our cohort included 1305 kidney transplant recipients. The primary outcome of this trial was graft loss, defined as the initiation of chronic dialysis or the need for retransplantation. The secondary outcome was the combination of death-censored graft loss and death with a functioning graft. During the study's follow-up period, there were 131 events of graft loss. The number of episodes of subtherapeutic tacrolimus level during the first-year posttransplantation was significantly associated with graft loss (HR 1.208 per episode, 95% CI 1.075–1.356, p = 0.001) and significantly improved the relative likelihood of the model compared to the multivariate model as demonstrated by the delta AIC value (8.256, p = 0.016). Conclusion: In addition to increased tacrolimus blood level variability, the number of episodes of subtherapeutic tacrolimus levels is independently associated with decreased graft survival among kidney transplant recipients.