Determination of the Optimal Dose of Calcineurin Inhibitor for Immunosuppressive Therapy with Basiliximab in Kidney Transplantation

Abstract

Background: Administration of basiliximab (BXM) decreases the acute rejection (AR) rate in kidney transplantation (KT). Therefore, compared to the immunosuppressive (IS) regimen without BXM, administration of a high dose of the IS drug with BXM in the initial postoperative period is not necessary. Long-term administration of calcineurin inhibitor (CNI) causes adverse effects the kidney function. Hence, the optimal dose of CNI must be reevaluated. Material and method: We analyzed 86 patients, who underwent KT at our center between January 1, 1990 and November 30, 2008. Of these, 43 patients were administered tacrolimus (Tac), whereas the other 43 patients were administered cyclosporine (CsA). We evaluated the beneficial effects of BXM by comparing the clinical results of the IS regimen with BXM (BXM group) and IS regimen without BXM (non-BXM group). The IS regimen consisted of steroids, CNI, and antimetabolites. We evaluated AR rate, presence of infection, trough levels of CNI, and kidney function. To determine the optimal dose of CNI, we divided the patients from the BXM group into the following 4 groups: high-dose Tac (n = 14, trough level ≥ 10.5 ng/ml), high-dose CsA (n = 13, trough level ≥ 200 ng/ml), low-dose Tac (n = 12, trough level < 10.5 ng/ml), and low-dose CsA (n = 18, trough level < 200 ng/ml). The above-mentioned parameters were also evaluated for these 4 groups. To determine the optimal dose of CNI which takes into consideration its effect and safety during the initial postoperative period, we measured the trough levels of CNI of the BXM group by performing a receiver operating characteristic (ROC) analysis. Results: Patients in the BXM group showed a significantly lower incidence of AR at 3 and 12 months after transplantation than those in the non-BXM group (p = 0.04 and p = 0.11, respectively). No significant differences were observed between the BXM and non-BXM groups with regard to infectious diseases and kidney function. The mean trough levels at 2 weeks after operation for patients in the BXM group with Tac (11.2 ± 3.1 ng/ml) were significantly lower than those in the non-BXM group with Tac (16.4 ± 4.2 ng/ml) (p < 0.001). Similarly, the mean trough levels at 2 weeks after operation for patients in the BXM group with CsA (204.4 ± 60.3 ng/ml) were significantly lower than those in the non-BXM group with CsA (272.2 ± 120.7 ng/ml) (p = 0.03). No significant differences were observed between the CNI-high and CNIlow groups in terms of the AR rate at 3 and 12 months after operation, infectious disease, and kidney function. The optimal doses of Tac and CsA, as determined from the ROC analysis, were 8.8˜11.5 ng/ml and 183.3˜200 ng/ml, respectively, in the initial postoperative period. Conclusion: The results of our study show that an IS regimen with BXM decreases the AR rate at 3 months after transplantation, without causing CMV and mycosis infection. Therefore, it is suggested that an IS regimen with BXM leads to decrease the CNI dose, without adversely affecting the clinical outcome.