Oshiro Y, Nakagawa K, Hoshinaga K, Aikawa A, Shishido S, Yoshida K, Asano T, Murai M, Hasegawa A
Faculty of Medicine, University of the Ryukyus, Urology, Nishihara, Okinawa, Japan.
Transplant Proc. 2013 May;45(4):1476-80. doi: 10.1016/j.transproceed.2013.03.016.
We examined the efficacy and safety of 4-drug combination therapy using high-dose mizoribine (MZR) (8 mg/kg/d), cyclosporine (CsA), basiliximab (BXM), and steroid (STR) in 39 renal transplant recipients. Acute rejection episodes (ARE), which occurred in 9 (23.1%) patients, correlated with lower blood levels of MZR (trough levels ≥ 2 μg/mL). In addition, lower MZR concentrations tended to be associated with a higher incidence of rejection episodes in children aged ≤ 10 years than in those aged ≥ 11 years. The area under the received operating characteristics (ROC) curve of MZR trough level to pred ARE was 0.825 (95% confidence interval, 0.690-0.962; P = .002). Based on the ROC analysis, are MZR cut-off of 1.6 μg/mL showed a sensitivity of 81.8% and a specificity of 75.0%. Adverse events were observed in 23 patients, including infections in 11 (7 patients positive for cytomegalovirus [CMV] antigen and 4 treated with anti-CMV drugs). The MZR trough levels seemed to be higher among patients with adverse events than in those free of them, but it was no significant. All patients experienced successful engraftment except 1 who died of unknown cause with a functioning graft. In conclusion, our study showed that low MZR trough levels correlated with the incidence of ARE. No serious adverse effects were encountered with this therapy.
我们在39例肾移植受者中研究了高剂量咪唑立宾（MZR）（8mg/kg/d）、环孢素（CsA）、巴利昔单抗（BXM）和类固醇（STR）四联疗法的疗效和安全性。9例（23.1%）患者发生急性排斥反应（ARE），这与较低的MZR血药浓度（谷浓度≥2μg/mL）相关。此外，与11岁及以上儿童相比，MZR浓度较低往往与10岁及以下儿童更高的排斥反应发生率相关。MZR谷浓度对预测ARE的受试者工作特征（ROC）曲线下面积为0.825（95%置信区间，0.690 - 0.962；P = 0.002）。基于ROC分析，MZR临界值为1.6μg/mL时，敏感性为81.8%，特异性为75.0%。23例患者观察到不良事件，包括11例感染（7例巨细胞病毒[CMV]抗原阳性，4例接受抗CMV药物治疗）。发生不良事件的患者MZR谷浓度似乎高于未发生不良事件的患者，但差异无统计学意义。除1例移植肾有功能但死因不明的患者外，所有患者移植均成功。总之，我们的研究表明，低MZR谷浓度与ARE的发生率相关。该疗法未遇到严重不良反应。
