Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji City, Tokyo, Japan.
Cell Transplant. 2012;21(2-3):565-70. doi: 10.3727/096368911X605493.
Basiliximab is a recently developed immunosuppressive agent for the prevention of acute allograft rejection in renal transplant recipients. The combination use of basiliximab and a calcineurin inhibitor was suggested to be more effective in comparison to immunosuppressive therapy using calcineurin inhibitor without basiliximab. Cyclosporine has been generally administered with basiliximab for renal transplant recipients. However, in cases of tacrolimus-based immunosuppressive regimen, the clinical efficacy and safety of combined use of tacrolimus and basiliximab remains to be elucidated. This study evaluated the tacrolimus pharmacological efficacy using a lymphocyte immunosuppressant sensitivity test (LIST) with MTT assay procedures in 16 cases of renal transplant recipients treated by tacrolimus without basiliximab and in 13 cases treated by tacrolimus in combination with basiliximab. The rate of acute rejection episodes in the recipients treated with tacrolimus plus basiliximab was 1/13 (7.7%), whereas the rate in the recipients treated with tacrolimus without basiliximab was 6/16 (37.5%). The recipients were divided into two groups according to their peripheral blood mononuclear cell (PBMC) sensitivity to tacrolimus [i.e., including a tacrolimus high sensitivity group (IC(50) <1.0 ng/ml) and a low sensitivity group (IC(50) >1.0 ng/ml). In the recipients treated with tacrolimus without basiliximab, the rate of acute rejection episodes in the tacrolimus high sensitivity group was 1/10 (10.0%), which was significantly lower than the rate in the low sensitivity group of 5/6 (83.3%; p = 0.008). The incidence of cytomegalovirus infection was not significantly different between the tacrolimus high and the low sensitivity groups of the recipients treated with tacrolimus with and without basiliximab. Therefore, in the case of selected tacrolimus-based immunosuppressive therapy for renal transplant recipients, the tacrolimus pharmacological efficacy should be evaluated using LIST at a time just before the transplant procedure in order to accurately predict allograft rejection. The data also suggested that low tacrolimus sensitivity recipients should be treated with tacrolimus-based immunosuppressive therapy in combination with basiliximab.
巴利昔单抗是一种最近开发的免疫抑制剂，用于预防肾移植受者的急性移植物排斥反应。与不使用巴利昔单抗的钙调神经磷酸酶抑制剂免疫抑制治疗相比，联合使用巴利昔单抗和钙调神经磷酸酶抑制剂更有效。环孢素通常与巴利昔单抗一起用于肾移植受者。然而，在他克莫司为基础的免疫抑制方案中，联合使用他克莫司和巴利昔单抗的临床疗效和安全性仍有待阐明。本研究通过 MTT 法检测淋巴细胞免疫抑制剂敏感性试验（LIST）评估了 16 例未用巴利昔单抗的他克莫司治疗和 13 例联合用巴利昔单抗的他克莫司治疗的肾移植受者的他克莫司药代动力学疗效。用巴利昔单抗联合他克莫司治疗的受者急性排斥反应发生率为 1/13（7.7%），而未用巴利昔单抗的受者发生率为 6/16（37.5%）。根据外周血单个核细胞（PBMC）对他克莫司的敏感性，将受者分为两组，即他克莫司高敏感组（IC50<1.0ng/ml）和低敏感组（IC50>1.0ng/ml）。在未用巴利昔单抗的他克莫司治疗的受者中，他克莫司高敏感组的急性排斥反应发生率为 1/10（10.0%），明显低于低敏感组的 5/6（83.3%；p=0.008）。用巴利昔单抗联合和不联合他克莫司治疗的受者中，巨细胞病毒感染的发生率在他克莫司高敏感组和低敏感组之间无显著差异。因此，在为肾移植受者选择以他克莫司为基础的免疫抑制治疗时，应在移植前评估 LIST 中的他克莫司药代动力学疗效，以准确预测移植物排斥反应。该数据还表明，低他克莫司敏感的受者应接受他克莫司为基础的免疫抑制治疗联合巴利昔单抗治疗。
