The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function

Abstract

Background. Calcineurin inhibitors are inherent vasoconstrictors. Cerebral vasoconstriction can reduce cerebral blood flow (CBF), and negatively impact cerebrovascular response (CVR) to exercise, and cognitive function. The once-daily extended-release (LCP) tacrolimus has fewer side effects than the immediate-release (IR) tacrolimus. The role of calcineurin inhibitors on CBF and the impact of specific formulations of tacrolimus on CBF, CVR, and cognitive function are unknown. In this pilot study, we evaluated whether changing from IR tacrolimus to LCP tacrolimus modulates CBF, CVR, or cognitive function in kidney transplant (KT) recipients. Methods. We randomized (2:1) 30 stable KT recipients on IR tacrolimus to intervention (switch to LCP tacrolimus) and control (continue IR tacrolimus) arms. We measured CBF, CVR, and cognitive function at baseline and at 12 wk. We used ANCOVA to evaluate changes in outcome variables, with baseline values and study arm as covariates. We used descriptive statistics with mean changes in outcome variables to compare the 2 groups. Results. Participants were 51 ± 13 y old. There was no difference in plasma tacrolimus levels at baseline and at 12 wk in the 2 arms. The changes in CBF, resting middle cerebral artery velocity, CVR, and cognitive function were more favorable in the intervention arm than in the control group. Conclusions. Changing IR tacrolimus to LCP tacrolimus may improve CBF, cerebrovascular dynamics, and cognitive function in KT recipients. Larger studies are needed to confirm these results.