High Tacrolimus Clearance Is a Risk Factor for Acute Rejection in the Early Phase After Renal Transplantation

Background: Patients with high tacrolimus clearance eliminate more drug within a dose interval compared to those with low clearance. Delays in dosing time will result in transient periods of lower concentrations in high- versus low clearance patients. Transient subtherapeutic tacrolimus concentrations may induce acute rejection episodes. Methods: A retrospective study in all renal transplant patients treated with tacrolimus at our centre from 2009 to 2013 was conducted. The association between individually estimated tacrolimus clearance (daily tacrolimus dose [mg] / trough concentration [µg/L]) and biopsy-proven acute rejection (BPAR) the first 90 days posttransplantation was investigated. Results: In total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into four groups according to their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a HR of 2.39 (95% CI; 1.30-4.40) compared to the low clearance group. Clearance estimate (as a continuous parameter) showed a hazard ratio of 2.25 (95% CI; 1.70-2.99) after adjusting for other risk factors. There were no significant differences in neither trough concentrations the first week after transplantation nor time to target trough concentration between patients later experiencing BPAR or not. Conclusion: High estimated clearance is significantly associated with increased risk of BPAR the first 90 days post-transplantation, and may predict an increased risk of rejection in the early phase following renal transplantation. This research has been accepted and published in Transplantation. © 2017 Lippincott, Williams & Wilkins