Montagnino Giuseppe, Sandrini Silvio, Iorio Beniamino, Schena Francesco Paolo, Carmellini Mario, Rigotti Paolo, Cossu Maria, Altieri Paolo, Salvadori Maurizio, Stefoni Sergio, Corbetta Giuseppe, Ponticelli Claudio
Nephrology Unit, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milan, 20122, Italy.
Nephrol Dial Transplant. 2008 Feb;23(2):707-14. doi: 10.1093/ndt/gfm621. Epub 2007 Sep 21.
Everolimus and cyclosporine exhibit synergistic immunosuppressive activity when given in combination. In this randomized trial, we explored whether the use of everolimus associated with low-dose cyclosporine could allow an early avoidance of steroids in de novo renal transplant recipients.
In this exploratory multicenter trial, 65 out of 133 patients treated with basiliximab (days 0 and 4), everolimus 3 mg/day and cyclosporine were randomized to stop steroids on the seventh post-transplant day (group A), whereas the remaining 68 continued low-dose steroid treatment (group B).
During the follow-up, 30 patients of group A (46%) resumed steroids. According to the intention-to-treat analysis, the 3-year graft survival rate was 95% in group A and 87% in group B (P = ns). There were more biopsy-proven rejections in group A, the difference being of borderline significance (32% vs 18%; P = 0.059). After 3 years, mean creatinine clearance was 52.3 +/- 17.1 ml/min in group A and 52.2 +/- 21.5 ml/min in group B. It was similar in the group A patients who experienced rejection (49.8 +/- 14.7 ml/min) and those who did not (53.6 +/- 18.3 ml/min; P = 0.319). Mean serum cholesterol and triglyceride levels were, respectively, less than 250 mg/dl and less than 200 mg/dl in both groups, without any significant difference. Vascular thrombosis (0 vs 11.7%; P = 0.0043) was more frequent in group B.
Treatment based on everolimus and low-dose cyclosporine allowed excellent renal graft survival and stable graft function at 3 years. An early discontinuation of steroids increased the risk of acute rejection, but was associated with a better graft survival in the long-term. However, it was well tolerated only by 54% of patients.
依维莫司与环孢素联合使用时表现出协同免疫抑制活性。在这项随机试验中，我们探讨了使用依维莫司联合小剂量环孢素是否能使初发肾移植受者早期避免使用类固醇。
在这项探索性多中心试验中，133例接受巴利昔单抗（第0天和第4天）、依维莫司3mg/天和环孢素治疗的患者中，65例被随机分配在移植后第7天停用类固醇（A组），其余68例继续低剂量类固醇治疗（B组）。
在随访期间，A组30例患者（46%）恢复使用类固醇。根据意向性分析，A组3年移植肾存活率为95%，B组为87%（P=无统计学意义）。A组活检证实的排斥反应更多，差异具有临界显著性（32%对18%；P=0.059）。3年后，A组平均肌酐清除率为52.3±17.1ml/分钟，B组为52.2±21.5ml/分钟。经历排斥反应的A组患者（49.8±14.7ml/分钟）和未经历排斥反应的患者（53.6±18.3ml/分钟；P=0.319）的情况相似。两组患者的平均血清胆固醇和甘油三酯水平分别低于250mg/dl和200mg/dl，无显著差异。B组血管血栓形成更频繁（0对11.7%；P=0.0043）。
基于依维莫司和小剂量环孢素的治疗在3年时可实现出色的移植肾存活和稳定的移植肾功能。早期停用类固醇增加了急性排斥反应的风险，但从长期来看与更好的移植肾存活相关。然而，只有54%的患者对其耐受性良好。
