Renal Function, Efficacy, and Safety of Sirolimus and Mycophenolate Mofetil After Short-Term Calcineurin Inhibitor-Based Quadruple Therapy in De Novo Renal Transplant Patients: One-Year Analysis of a Randomized Multicenter Trial
Renal Function, Efficacy, and Safety of Sirolimus and Mycophenolate Mofetil After Short-Term Calcineurin Inhibitor-Based Quadruple Therapy in De Novo Renal Transplant Patients: One-Year Analysis of a Randomized Multicenter Trial
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DOI：
10.1097/tp.0b013e3181e11798
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发表时间：
2010-07-27
期刊：
影响因子：
6.2
通讯作者：
Jauch, Karl-Walter
中科院分区：
文献类型：
--
作者：
Guba, Markus;Pratschke, Johann;Jauch, Karl-Walter
背景资料。无钙调神经磷酸酶抑制剂方案中的新西罗莫司，虽然对改善早期肾功能有潜在的作用，但有多种药物相关的副作用。我们报告了一项前瞻性的开放标签、多中心、随机试验，以评估肾移植后10至24天从基于CsA的方案到基于西罗莫司(SRL)的方案的早期转换。在196名患者中，141名免疫风险低至中等的患者有资格转换为SRL或继续CSA。所有患者均接受抗胸腺细胞球蛋白-F单剂诱导、霉酚酸酯和类固醇治疗。在12个月时，SRL组的主要终点、S肌酐测定的肾功能和南基维尔公式计算的肾小球滤过率(1.51+/-0.59比1.87+/-0.98 mg/dL或64.5+/-25.2比53.4+/-18.0mL/min/1.73m(2))明显好于SRL组。患者存活率、移植物存活率和转归后活检证实的急性排斥反应的发生率在统计学上没有差异。SRL组的药物停用率显著高于SRL组(36.2%vs.19.7%)。值得注意的是，SRL组更多的患者报告了痤疮、隐匿性和暂时性高脂血症，而巨细胞病毒血症显著减少(7.3%比28.2%)。早期转换为无钙调神经磷酸酶抑制剂的方案与SRL联合霉酚酸酯可能是改善肾功能的一个有用的策略。确定合适的候选者和安全管理SRL相关的不良事件将是避免高辍学率的关键，目前高辍学率限制了该方案的广泛适用性。
Background. De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects.Methods. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids.Results. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51 +/- 0.59 vs. 1.87 +/- 0.98 mg/dL or 64.5 +/- 25.2 vs. 53.4 +/- 18.0 mL/min/1.73 m(2)). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%).Conclusions. Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.