*Purpose: Increased coefficient of variation (CV) of tacrolimus (FK) levels, indicating high intra-patient FK level fluctuations, are associated with increased rejection, development of donor-specific antibodies, and graft loss. Use of once-daily tacrolimus formulations like LCP-Tac results in lower intra-day peak to trough fluctuations and increased bioavailability compared to immediate release tacrolimus (Tac-IR) but it is unknown whether use of LCP-Tac results in a favorable CV and outcomes compared to Tac-IR.

*Methods: We performed a retrospective cohort study of adults who underwent kidney transplant at a single center from 1/2015 to 6/2017 who received tacrolimus in the first year post-transplant. We evaluated Tac-IR and LCP-Tac for differences in CV at 3, 6, and 12 months; CV was calculated as the tacrolimus level [σ/μ] x 100. The impact of CV ≥ 30% on patient outcomes including graft function, rejection, and graft loss were assessed. Multivariable regression analysis was utilized to confirm the impact of CV ≥ 30% on outcomes.

*Results: We included 445 patients (229 LCP-Tac and 216 Tac-IR) maintained on a consistent formulation of tacrolimus during their first year post-transplant. LCP-Tac patients were older with a higher PRA; there were no differences in induction therapy, race, dialysis vintage, or donor type. Acute cellular rejection occurred in 5.6% of the cohort, antibody mediated rejection in 3.1%, and graft loss in 4.3% of patients. There were no differences between formulations in rejection, graft failure, or renal function. At 3, 6, and 12 months post-transplant, LCP-Tac had significantly higher CV (3 month, 30.3% vs. 23.9%, 6 months 26.7% vs. 22.0%, 12 months 25.9% vs. 20.7%). Patients with CV ≥ 30% in the first post-transplant year were more likely to have rejection but overall had similar renal function. On multivariate analysis, CV ≥ 30% remained significantly associated with rejection (OR 2.92 (1.20-7.08) P=0.018).

*Conclusions: Increased tacrolimus level CV is a predictor of rejection after kidney transplantation. Despite a more favorable pharmacokinetic profile, LCP-Tac did not improve CV compared to Tac-IR. LCP-Tac patients experienced significantly higher coefficient of variations but similar rates of rejection compared to Tac-IR. Further studies are warranted to elucidate how to best identify and manage risk factors for high CV and associated rejection episodes.

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