Induction therapy followed by maintenance with a calcineurin inhibitor aims to minimize the incidence of early rejection and optimize the potential for allograft function. However the optimal timing for maintenance therapy, and risking associated nephrotoxicity, is unclear. The goal of this study was to examine whether delayed achievement of therapeutic tacrolimus (FK) levels was associated with an increased risk of early acute rejection episodes following renal transplantation.

This is a retrospective study of single-center results from 2004-2015, expanding upon a previous study with double the number of patients. The primary outcome was early acute rejection, defined as requiring treatment with or without pathologic confirmation within 120 days. For the purpose of study, patients were grouped into tertiles based on achievement of therapeutic FK levels: within 7 days, between 7-14 days, and beyond 14 days. Other variables included induction agent, occurrence of delayed graft function (DGF), donor type, recipient age, blood type compatibility, number of human leukocyte antigen (HLA) mismatches, highest panel reactive antibody, and ischemia times. Cox proportional hazards regression was used for multivariate data analysis.

This study included 1306 patients, 77% of whom received deceased-donor allografts. Anti-thymocyte globulin and basilixumab were used in 80% and 20% of cases, respectively. At 0-7, 7-14, and >=14 days, therapeutic FK levels were achieved by 38, 41, and 21%, respectively. Sixteen percent of patients exhibited DGF. Only HLA mismatch >= 5 (RR 1.42; p = 0.03) and DGF (RR 1.47; p = 0.05) were significantly associated with a higher risk of early rejection. The groups did not differ based on timing of first therapeutic FK level. Sub-group analysis was performed on all recipients with post-transplant DGF. Delay to therapeutic FK level beyond 14 days was associated with a lower incidence of early rejection (RR 0.19; p=0.008).

Delay to therapeutic FK levels was not shown to confer an increased risk of early cell-mediated rejection. More caution should be given to early FK initiation in the setting of adequate induction therapy and/or DGF. In patients with DGF, delay to sufficient maintenance therapy may be protective against early rejection.

CITATION INFORMATION: Marshall R., Brandenberger J., Cantafio A., Halldorson J., Bakthavatsalam R., Dick A., Rayhill S., Reyes J., Perkins J. Delayed Achievement of Therapeutic Tacrolimus Levels after Renal Transplantation is Not Associated with Increased Incidence of Early Acute Rejection: Single-Center Results Am J Transplant. 2017;17 (suppl 3).

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