南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (12): 1842-.

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肾移植受者应用霉酚酸酯的合理治疗窗

于立新,周敏捷,罗敏   

  • 出版日期:2014-12-20 发布日期:2014-12-20

Therapeutic window of mycophenolate mofetil for preventing acute graft rejection
following renal transplantation

  • Online:2014-12-20 Published:2014-12-20

摘要: 目的确定肾脏移植受者应用霉酚酸酯(MMF)的合理治疗窗浓度。方法选取110例肾移植受者分别于术后1月内、2~3
个月、>4个月应用酶放大免疫分析技术测定口服MMF(分两次服用,间隔12 h)12 h后全血谷浓度(即MPA-C0),并观察受者用
药期间急性排斥反应及药物毒副反应发生情况,对所有受者随访时间均为1年。结果统计资料显示,术后急性排斥反应发生
率为13.64%(15/110),药物毒副反应发生率为32.73%(36/110),其中白细胞减少症12例,MMF相关性腹泻10例,感染10例,肝
功能损害4例。发生急性排斥反应受者予甲基强的松龙冲击治疗后均成功逆转,药物毒副反应受者经治疗和(或)调整MMF剂
量后病情恢复,无死亡病例及移植肾摘除病例。通过ROC曲线计算得出,MPA-C0控制在1.40~2.80 mg/L可较好避免肾移植术
后急性排斥反应并减少受者的药物毒副反应。结论对肾移植术后服用MMF的受者进行MPA-C0监测,对MMF用量进行个体
化调整,有利于预防急性排斥反应和药物毒副反应发生,减少并发症,提高移植肾及受者的存活率。

Abstract: Objective To determine the optimal dose range (therapeutic window) of mycophenolate mofetil (MMF) for
preventing acute graft rejection following renal transplantation. Methods The trough concentration of MMF (MPA-C0) at 12 h
after oral administration of the drug (two doses daily given at an interval of 12 h) was monitored in 110 renal transplant
recipients within a month, in 2-3 months, and over 4 months after the transplantation using EMIT method. The occurrence of
acute graft rejection and drug toxicity were observed in all the patients during the one-year follow-up. Results The incidence
of acute graft rejection after transplantation was 13.64% (15/110) in these patients. Drug toxicity and complications occurred in
32.73% (36/110) of the patients, including 12 cases with reduced white blood cell counts, 10 with MMF cid-associated diarrhea,
10 with infection, 4 with liver function damage. Acute rejection was successfully reversed after methylprednisolone treatment
and drug toxicity was managed by corresponding treatment and adjustment of MMF dose. No deaths or graft removal
occurred in these patients. The ROC curve showed that a MPA-C0 of 1.40-2.80 mg/L was optimal in preventing acute rejection
after the transplantation and reducing adverse drug effects. Conclusion Monitoring MPA-C0 and individualized MMF dosing
help to prevent acute graft rejection, reducing drug toxicity and complications, and improving graft survival rate after renal
transplantation.