Department of Surgery, Munich University Hospital, Campus Grosshadern, Munich, Germany.
Transpl Int. 2012 Apr;25(4):416-23. doi: 10.1111/j.1432-2277.2012.01432.x. Epub 2012 Feb 10.
Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen.
早期转换为西罗莫司（SRL）、霉酚酸酯（MMF）和类固醇组成的无钙调磷酸酶抑制剂（CNI）维持免疫抑制方案与基于环孢素（CsA）的方案（SMART 核心研究）相比，可改善 1 年的肾功能。这项观察性随访研究在 SMART 研究框架内对 132 例患者进行了 36 个月的随访。在 36 个月时，SRL 治疗组的肾功能持续优于 CsA 组[意向治疗（ITT）eGFR（@36m）：60.88 与 53.72（CsA）ml/min/1.73m（2），P=0.031]。然而，SRL 组停药的患者明显多于 CsA 组[59.4%与 42.3%（CsA）]。在 36 个月时，两组患者[99%（SRL）与 97%（CsA）和移植物 96%（SRL）与 94%（CsA）]的存活率均非常高。晚期排斥反应的发生率在两组间无差异。晚期感染和不良事件在两组间相似，除 SRL 组高脂血症发生率较高和 CsA 治疗组恶性肿瘤发病率较高外。在多变量分析中，供者年龄>60 岁、转换时 S-肌酐>2mg/dl、CMV 未感染（-）受者以及 CsA 免疫抑制是 36 个月时肾功能受损的预测因素。早期转换为无 CNI 的 SRL 为基础的免疫抑制方案可使移植后 36 个月肾功能持续改善。使用这种 mTOR 抑制剂为基础的免疫抑制方案，患者选择将是获得长期获益和避免治疗失败的关键。
