Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients

Background A multivariable linear regression model including baseline and immunosuppression-related predictors of the post-kidney transplant tacrolimus dose/day required for achieving a target tacrolimus trough level of 4-8 ng/mL (currently accepted reduced tacrolimus dosing strategy) would provide a practical guide to clinicians. Methods Using our prospectively followed cohort of 578 adult primary kidney transplant recipients assigned to receive reduced tacrolimus dosing as part of maintenance therapy, we determined the significant predictors of absolute tacrolimus dose (mg), tacrolimus trough level (ng/mL), and dose-adjusted tacrolimus trough level (%/L) during the first 36 months post-transplant. Results Two demographic variables were associated with a significantly higher tacrolimus dose at each post-transplant time analyzed: African American recipient (p < 0.000001) and younger recipient age (p = 0.00009). Use of maintenance corticosteroids was also associated with a significantly higher tacrolimus dose but only during the first 12 months post-transplant (p = 0.002). None of the other baseline variables (or use of sirolimus) were predictive of tacrolimus dose, and none of these factors were associated with the tacrolimus trough level (thus, effective therapeutic drug monitoring was achieved). Results for dose-adjusted tacrolimus trough level were inversely related to the tacrolimus dose findings. Conclusions Significantly higher tacrolimus dosing to achieve the target tacrolimus trough level (lower bioavailability) was required, but only among African Americans, younger recipients, and those receiving maintenance corticosteroids.