Lebranchu Y
University Hospital of Tours, François Rabelais University of Tours, Tours, France.
Transplant Proc. 2010 Nov;42(9 Suppl):S25-8. doi: 10.1016/j.transproceed.2010.07.002.
Calcineurin inhibitors (CNIs) and steroids, the cornerstone of most immunosuppressive regimens in the past 20 years, have undesirable chronic effects. This has led to the use of new strategies with sirolimus (SRL) and mycophenolate mofetil (MMF). In the SPIESSER study, de novo CNI avoidance and early steroid withdrawal were evaluated in 145 renal recipients randomized to receive either SRL (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal antithymocyte globulin for 5 days, MMF, and steroids withdrawn at 6 months. At 12 months, the incidence of biopsy-proven acute rejection was low (14.3% for SRL vs 8.6% for CsA). At 3 years, renal function (Nankivell) was better in the SRL group, particularly in patients who remained on treatment according to the protocol (71 ± 22 vs 60 ± 17 mL/min; P < .01). Steroids were withdrawn in 70.5% of SRL-treated patients and in 66.7% of CsA-treated patients. In the CONCEPT study, early conversion from CsA to SRL was evaluated in 192 renal recipients prospectively randomized at week 12 to switch from CsA to SRL (n = 95) or to continue CsA (n = 97). At 12 months, estimated glomerular filtration rate (Modification of Diet in Renal Disease) was significantly higher with SRL (61 ± 16 vs 54 ± 15 mL/min; P = .002, intent-to-treat analysis). The significant improvement in renal function was maintained at 30 months. In both studies graft and patient survival were similar, with better renal function and a tendency for fewer cancers observed at follow-up in patients receiving a maintenance regimen with SRL and MMF. At 30 months, steroids had been withdrawn in 72% of SRL-treated patients and in 70% of CsA-treated patients.
钙调神经磷酸酶抑制剂（CNIs）和类固醇是过去20年中大多数免疫抑制方案的基石，但它们具有不良的慢性影响。这促使人们采用西罗莫司（SRL）和霉酚酸酯（MMF）等新策略。在SPIESSER研究中，对145例肾移植受者进行了评估，这些受者被随机分为接受SRL组（n = 71）或环孢素（CsA；n = 74）组，以避免从头使用CNI并早期停用类固醇。所有患者均接受多克隆抗胸腺细胞球蛋白治疗5天、MMF治疗，类固醇在6个月时停用。在12个月时，经活检证实的急性排斥反应发生率较低（SRL组为14.3%，CsA组为8.6%）。在3年时，SRL组的肾功能（Nankivell法）更好，特别是那些按照方案继续治疗的患者（71±22 vs 60±17 mL/分钟；P <.01）。70.5%接受SRL治疗的患者和66.7%接受CsA治疗的患者停用了类固醇。在CONCEPT研究中，对192例肾移植受者进行了早期从CsA转换为SRL的评估，这些受者在第12周被前瞻性随机分为从CsA转换为SRL组（n = 95）或继续使用CsA组（n = 97）。在12个月时，SRL组的估计肾小球滤过率（肾脏病饮食改良法）显著更高（61±16 vs 54±15 mL/分钟；P =.002，意向性分析）。在30个月时，肾功能的显著改善得以维持。在两项研究中，移植物和患者生存率相似，在接受SRL和MMF维持治疗方案的患者随访中，观察到肾功能更好且癌症发生率有降低趋势。在30个月时，72%接受SRL治疗的患者和70%接受CsA治疗的患者停用了类固醇。
