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.

CYP3A5 *1 Allele: Impacts on Early Acute Rejection and Graft Function in Tacrolimus-Based Renal Transplant Recipients

“…Undre et al (27) previously reported that the mean AUC 0 -12 of tacrolimus on day 2 posttransplant was significantly lower in patients who had experienced acute AR. Borobia et al (28) also showed that tacrolimus trough concentrations during the first week are an important predictor of AR.…”

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

“…Patients with a Tac C 0 below 9.3 ng/mL on day 5 showed a shorter graft survival in comparison with patients with Tac C 0 above this concentration [26]. A similar conclusion was also drawn by Staatz et al, who estimated that a rejection rate as high as 55% would be found for patients with a Tac C 0 between 0 and 10 ng/ml, compared with no observed rejection in patients with a Tac C 0 between 10 and 15 ng/ml in the first month after kidney transplantation [25].…”

Dosing equation for tacrolimus using genetic variants and clinical factors

“…Higher troughs are associated with increased risk of toxicity whereas lower troughs are associated with increased risk of rejection [4]. Two recent studies showed that with contemporary immunosuppressive regimens (tacrolimus, mycophenolate and steroids Ϯ antibody induction) low tacrolimus troughs in the first week post transplant were associated with a greater risk of acute rejection [5,6].To tailor therapy better, multiple clinical factors have been explored to determine their effects on tacrolimus pharmacokinetics. It is generally acknowledged that drug interactions, haematocrit, corticosteroid therapy, days post transplant, and race affect tacrolimus pharmacokinetics [3, [7][8][9][10].…”