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

• Published in: Transplantation 2017-08, Vol.101 (8), p.e273-e279
• Main Authors: Egeland, Erlend Johannessen, Robertsen, Ida, Hermann, Monica, Midtvedt, Karsten, Størset, Elisabet, Gustavsen, Marte Theie, Reisæter, Anna Varberg, Klaasen, Rolf, Bergan, Stein, Holdaas, Hallvard, Hartmann, Anders, Åsberg, Anders
• Format: Article
• Language: English
• Subjects: Acute Disease; Biopsy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Graft Rejection - diagnosis; Graft Rejection - metabolism; Graft Rejection - prevention & control; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Incidence; Kidney Transplantation - adverse effects; Male; Middle Aged; Norway - epidemiology; Retrospective Studies; Risk Factors; Tacrolimus - administration & dosage; Tacrolimus - pharmacokinetics; Time Factors
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0000000000001796

BACKGROUNDPatients with high tacrolimus clearance eliminate more drug within a dose interval compared with 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. METHODSA retrospective study in all renal transplant patients treated with tacrolimus at our center 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. RESULTSIn total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into 4 groups per their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of 2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group. Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95% confidence interval, 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. CONCLUSIONSHigh estimated clearance is significantly associated with increased risk of BPAR the first 90 days posttransplantation and may predict an increased risk of rejection in the early phase after renal transplantation.