title: Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection.
abstract: There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug. After univariate analysis, donor age, duration of hospital stay, and creatinine clearance (third month) showed significant differences between rejecters and nonrejecters. In addition, mean tacrolimus trough concentrations on day 5, day 7, mean of days 1-7, and mean of days 5-7 were found to be significantly lower in rejecters (P = 0.009, P = 0.012, P = 0.006, and P = 0.035, respectively). Receiver operating characteristic curve analysis with tacrolimus trough concentrations measured on days 5 and 7 was able to discriminate between patients with and without acute rejection (P = 0.028 and P = 0.048 after Bonferroni correction). The tacrolimus trough concentration with the best sensitivity-specificity balance was 9.3 ng/mL on day 5 and 8.7 ng/mL on day 7. In the Kaplan-Meier analysis, patients with tacrolimus trough concentrations below 9.3 mg/mL on day 5 showed a lower survival time without acute rejection (P = 0.048 after correction) in comparison with patients with tacrolimus trough concentrations above this concentration. After logistic regression, we obtained a model relating rejection with sex, donor age, and tacrolimus trough concentrations on day 5 (P = 0.004). No significant relationship between tacrolimus trough concentrations and delta creatinine clearance from week 1 to month 3 was obtained. These results confirm that tacrolimus trough concentrations during the first week are an important predictor of acute rejection. Therefore, it is critical to reach target blood concentrations of tacrolimus as soon as possible to improve allograft survival.
authors.affiliation: Clinical Pharmacology Service, School of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Borobia
authors.forename: Ivan
authors.initials: I
authors.lastname: Romero
authors.forename: Carlos
authors.initials: C
authors.lastname: Jimenez
authors.forename: Fernando
authors.initials: F
authors.lastname: Gil
authors.forename: Elena
authors.initials: E
authors.lastname: Ramirez
authors.forename: Raquel
authors.initials: R
authors.lastname: De Gracia
authors.forename: Fernando
authors.initials: F
authors.lastname: Escuin
authors.forename: Elena
authors.initials: E
authors.lastname: Gonzalez
authors.forename: Antonio J Carcas
authors.initials: AJ
authors.lastname: Sansuán
mesh_terms: D006084:Graft Rejection / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents; D016030:Kidney Transplantation; D011183:Postoperative Complications; D016559:Tacrolimus / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus