Background: Tacrolimus (FK) is the drug of choice for preventing acute allograft rejection in kidney transplantation. However, therapeutic drug monitoring is necessary due to FK’s narrow-therapeutic index and erratic dose-concentration relationship, yet there is paucity in the data exploring the relationship between tacrolimus concentration variability and clinical outcomes.

Methods: This was a post-hoc pharmacokinetic analysis as part of a prospective, risk stratified, randomized, open label study of 200 kidney transplants. All patients randomly received either rATG or IL-2RA in addition to FK, MMF, and corticosteroids. High within-subject variability was defined as coefficient of variation > 40% for FK whole blood levels. Outcome analysis includes safety, efficacy, and QOL. Results are reported at one year post-transplant unless specified.

Results: Due to early graft loss, 2 of the 200 originally enrolled patients did not have FK concentrations for analysis. Baseline characteristics were similar between both groups except the high FK variability group had more African American patients and fewer patients with pre-transplant diabetes. Highly variable FK concentrations were associated with the development of DGF and diminished renal function through one year post-transplant. This relationship remained significant after controlling for baseline differences in race and pre-transplant diabetes (p < 0.05). FK concentration variability did not influence patient/graft survival, acute rejections, toxicities, or QOL.

Conclusion: Highly variable tacrolimus concentrations are associated with risk of developing DGF and diminished graft function. FK concentration variability does not appear to influence other clinical outcomes or QOL.

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