Yamani M H, Starling R C, Goormastic M, Van Lente F, Smedira N, McCarthy P, Young J B
Department of Cardiology and Cardiothoracic Surgery, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, OH 44195, USA.
Transplantation. 2000 Jun 15;69(11):2326-30. doi: 10.1097/00007890-200006150-00018.
Mycophenolate mofetil (MMF) is a unique immunosupressive agent that has been shown to be efficacious in the treatment of cardiac allograft rejection. The utility of therapeutic drug monitoring on rejection prophylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation.
Between May 1998 and February 1999, we retrospectively analyzed the clinical outcome of 215 heart transplant patients who had routine monitoring of MMF trough level at the time of scheduled endomyocardial biopsy. Patients were divided into three groups according to the time interval post transplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 months post transplant; and Group III, 71 patients beyond one year of transplant. Fifty patients had samples in more than one group. Rejection was defined as Grade > or = 3A based on ISHLT criteria. Mean follow-up period was 179+/-52 days.
A significantly decreased incidence of rejection was noted in the samples with MMF trough level > or = mg/l compared to those with less than 2 mg/l inpatients evaluated within the first year of transplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was > or = 2 mg/l compared to samples with MMF trough level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS).
Monitoring of MMF trough levels may play a role in the management of cardiac transplant recipients during the first year post transplant.
霉酚酸酯（MMF）是一种独特的免疫抑制剂，已被证明在治疗心脏移植排斥反应方面有效。治疗药物监测在预防和治疗排斥反应中的作用尚无定论。本研究旨在评估心脏移植后与MMF谷浓度相关的排斥反应发生率。
1998年5月至1999年2月期间，我们回顾性分析了215例心脏移植患者的临床结局，这些患者在预定的心内膜心肌活检时常规监测MMF谷浓度。根据移植后的时间间隔将患者分为三组，并根据MMF谷浓度进行评估。第一组，104例移植后6个月内的患者；第二组，90例移植后6至12个月的患者；第三组，71例移植后一年以上的患者。50例患者在多个组中有样本。根据国际心脏和肺移植学会（ISHLT）标准，排斥反应定义为≥3A 级。平均随访期为179±52天。
在移植后第一年评估的患者中，与MMF谷浓度低于2mg/l的患者相比，MMF谷浓度≥2mg/l的样本中排斥反应发生率显著降低（第一组：8.8%对14.9%，第二组：4.2%对11.3%，P均=0.05）。在有治疗性环孢素（CSA）或他克莫司（FK）血药浓度的情况下，与MMF谷浓度<2mg/l的样本相比，当MMF谷浓度≥2mg/l时，排斥反应发生率显著降低（3.6%对14.4%，P=0.005）。在CSA或FK血药浓度低于治疗水平时，未观察到显著差异（15.4%对13.9%，P=无统计学意义）。
监测MMF谷浓度可能在心脏移植受者移植后第一年的管理中发挥作用。
