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霉酚酸酯单药治疗肝移植后钙调神经磷酸酶抑制剂的严重副作用。

Mycophenolate mofetil monotherapy for severe side effects of calcineurin inhibitors following liver transplantation.

作者信息

Dharancy S, Iannelli A, Hulin A, Declerck N, Schneck A S, Mathurin P, Boleslawski E, Gugenheim J, Pruvot F R

机构信息

Maladies de l'Appareil digestif et de la Nutrition, Hôpital Claude Huriez, CHRU Lille, France.

出版信息

Am J Transplant. 2009 Mar;9(3):610-3. doi: 10.1111/j.1600-6143.2008.02529.x.

Abstract

Withdrawal of calcineurin inhibitors (CNI) followed by mycophenolate mofetil (MMF) monotherapy after liver transplantation (LT) remains controversial due to the increased risk of acute rejection and graft loss. The aim of the present study, performed in a large cohort of liver-transplanted patients with severe CNI-induced side effects, was to assess renal function recovery, and safety in terms of liver function, of complete CNI withdrawal and replacement by MMF monotherapy. Fifty-two patients treated with MMF monotherapy for CNI-induced toxicity were analyzed. Mean estimated glomerular filtration rate (eGFR) increased significantly during the period of MMF monotherapy, from 37 +/- 10 to 44.7 +/- 15 mL/min/1.73 m(2) at 6 months (p = 0.001) corresponding to a benefit of +17.4% in renal function. eGFR stabilized or improved in 86.5%, 81% and 79% of cases, and chronic renal dysfunction worsened in 13.5%, 19% and 21% of cases, at 6, 12 and 24 months after CNI withdrawal, respectively. Only two patients experienced acute rejection. MMF monotherapy may be efficient at reversing/stabilizing CRD, and appears relatively safe in terms of liver graft function in long-term liver-transplanted patients. However, clinicians must bear in mind the potential risk of rejection and graft loss, and should be very cautious in the management of such 'difficult-to-treat patients'.

摘要

肝移植(LT)后停用钙调神经磷酸酶抑制剂(CNI),继以霉酚酸酯(MMF)单药治疗,因急性排斥反应和移植物丢失风险增加而仍存在争议。本研究在一大群有严重CNI诱导副作用的肝移植患者中进行,旨在评估完全停用CNI并换用MMF单药治疗后的肾功能恢复情况以及肝功能方面的安全性。分析了52例因CNI诱导毒性接受MMF单药治疗的患者。在MMF单药治疗期间,平均估计肾小球滤过率(eGFR)显著增加,6个月时从37±10增至44.7±15 mL/min/1.73 m²(p = 0.001),相当于肾功能获益17.4%。在停用CNI后的6、12和24个月,分别有86.5%、81%和79%的病例eGFR稳定或改善,13.5%、19%和21%的病例慢性肾功能障碍恶化。仅2例患者发生急性排斥反应。MMF单药治疗可能有效地逆转/稳定慢性肾功能障碍,并且对于长期肝移植患者的肝移植物功能而言似乎相对安全。然而,临床医生必须牢记排斥反应和移植物丢失的潜在风险,并且在管理此类“难治性患者”时应非常谨慎。

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