肾移植患者霉酚酸谷浓度与急性排斥反应及药物毒性相关性的研究

Relationship between mycophenolic acid plasma trough level with rejection and toxicity in renal transplant patients

目的评价肾移植术后对霉酚酸酯（MMF）进行药物浓度监测的意义。方法 107例肾移植患者分别于术后1、2、3、4-6、7-12个月5个时间段内化验霉酚酸谷浓度（MPA-C0）,并记录患者期间发生的急性排斥及药物毒性事件,将患者分为排斥组（Ⅰ组）、药物毒性组（Ⅱ组）、正常组（Ⅲ组）。比较各组MPA-C0水平。结果排斥发生率为12.1%（13/107）,药物毒性发生率为35.5%（38/107）。Ⅰ组和Ⅲ组（1个月）、Ⅱ组和Ⅲ组间MPA-C0水平均有统计学差异（P〈0.05）;ROC曲线显示,MPA-C0水平为1.55 mg/L是识别排斥反应是否发生的最佳截断值,MPA-C0水平为2.50 mg/L是识别毒副反应是否发生的最佳截断值。结论对肾移植术后服用MMF的患者进行MPA-C0监测,对MMF用量进行个体化调整,有利于预防排斥反应和药物毒性发生,减少并发症,提高移植肾存活率。

Objective To evaluate the role of drug concentration monitoring of mycophenolate mofetil（MMF） in renal transplantation patients.Methods Mycophenolic acid plasma trough level（MPA-C0） of 107 renal transplantation patients at the time of month 1,month 2,month 3,month 4-6,and month 7-12 was monitored,and drug toxicity and rejection events during each period were recorded.According to rejection and drug toxicity events occured or not,the patients were divided into rejection group（groupⅠ）,toxicity group（groupⅡ） and control group（groupⅢ）.Then MPA-C0 level was compared between groups.Results Incidence of rejection was 12.1%（13/107） and incidence of drug toxicity was 35.5%（38/107）.There was significantly different between groupⅠ and group Ⅲ（month 1）,groupⅡ and groupⅢ.ROC curve showed a MPA level of 1.55 mg/L early post-transplantation best discriminated patients with and without rejection,and an MPA level of 2.50 mg/L best discriminated patients with and without toxicity later post-transplantation.Conclusion Monitoring of MPA-C0 and individual dose adjustment could be helpful to reduce complications and improve graft survival rate.