Sugiyama K, Tsukaguchi M, Sasahara H, Isogai K, Toyama A, Satoh H, Saito K, Nakagawa Y, Takahashi K, Tanaka S, Onda K, Hirano T
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Division of Pharmacy, Niigata University Medical and Dental Hospital, Niigata, Japan.
Drug Res (Stuttg). 2015 Dec;65(12):629-34. doi: 10.1055/s-0034-1395686. Epub 2014 Dec 30.
The lymphocyte immunosuppressant sensitivity test has been used to predict the pharmacodynamics of immunosuppressive drugs for the purpose of preventing acute rejection and infection after renal transplantation. On the other hand, measuring the ATP levels in peripheral CD4+ lymphocytes is also able to monitor the risks of rejection and infection in transplant recipients. In the present study, we examined the relationship between the mycophenolic acid pharmacodynamics and the ATP levels in peripheral lymphocytes before and after renal transplantation.
We examined both the pharmacological efficacy of mycophenolic acid and the lymphocyte ATP levels before and 2, 4 and 6 weeks after the operation in 20 renal transplant recipients. The drug's pharmacological efficacy was evaluated by the 50% inhibitory concentration of the drug against the in vitro proliferation of peripheral blood lymphocytes activated by T cell mitogen. The ATP levels in peripheral CD4+ lymphocytes were measured by the Immuknow assay kit. The relationships between the mycophenolic acid pharmacodynamics and ATP levels in peripheral lymphocytes were examined in these recipients.
The immunosuppressive effects of mycophenolic acid against mitogen-activated lymphocyte proliferation were significantly and positively correlated with the lymphocyte ATP levels, but only at 6 weeks after transplantation. The relationship was not significant before or at 2 or 4 weeks after the operation.
Our present data raised the possibility that evaluating the pharmacological efficacy of mycophenolic acid pre-transplantation and monitoring the ATP level 6 weeks after transplantation can predict the risk of rejection and/or infection in renal transplant recipients.
淋巴细胞免疫抑制剂敏感性试验已被用于预测免疫抑制药物的药效学,以预防肾移植术后的急性排斥反应和感染。另一方面,测量外周血CD4+淋巴细胞中的ATP水平也能够监测移植受者发生排斥反应和感染的风险。在本研究中,我们检测了肾移植前后霉酚酸的药效学与外周淋巴细胞中ATP水平之间的关系。
我们检测了20例肾移植受者术前及术后2周、4周和6周时霉酚酸的药理疗效以及淋巴细胞ATP水平。通过药物对T细胞有丝分裂原激活的外周血淋巴细胞体外增殖的50%抑制浓度来评估药物的药理疗效。采用Immuknow检测试剂盒测量外周血CD4+淋巴细胞中的ATP水平。在这些受者中检测霉酚酸的药效学与外周淋巴细胞中ATP水平之间的关系。
霉酚酸对有丝分裂原激活的淋巴细胞增殖的免疫抑制作用与淋巴细胞ATP水平呈显著正相关,但仅在移植后6周时如此。术前及术后2周或4周时这种关系不显著。
我们目前的数据提示,术前评估霉酚酸的药理疗效并在移植后6周监测ATP水平,有可能预测肾移植受者发生排斥反应和/或感染的风险。