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目的 观察西罗莫司(SRL)替代钙调神经素免疫抑制剂(CNI)作为肾移植术后早期肾功能稳定的患者抗排斥治疗方案的可行性和安全性.方法 前瞻性、开放性的临床对照研究,选取2008年6月至2011年6月浙江大学医学院附属第一医院共112例肾移植术后早期(3～6个月)肾功能稳定的患者纳入该研究,其中57例使用SRL替代CNI治疗作为试验组,另外55例继续使用CNI药物作为对照组,切换后霉酚酸酯和激素治疗剂量均无调整.所有患者至少随访24个月,评估两组患者纳入研究后1、6、12和24个月时急性排斥反应的发生率、人/肾存活率、肾功能、血脂、血糖、肝功能、尿蛋白的改变,同时观察有无不良事件发生.结果 试验组采用SRL切换治疗后动态随访肾功能显示切换前、切换后1、6、12、24个月血肌酐水平分别为(117.0±16.3)、(89.2±24.7)、(87.6±23.8)、(86.1±20.4)、(86.7±19.7) μmol/L,切换后血肌酐水平均明显低于切换前(均P＜0.05).对照组所有时间点均未显示肾功能改善.估算的肾小球滤过率(eGFR)试验组也较切换前显著提高,明显优于对照组(均P＜0.05).排斥反应共发生3例,试验组2例,对照组1例,差异无统计学意义(P＞0.05).试验组切换后1个月血脂明显升高(P＜0.05),经干预治疗后血脂与切换前差异无统计学意义(P＞0.05).试验组切换后血红蛋白有一定下降,但在正常范围,此外发生低钾血症2例,口腔溃疡2例,轻度蛋白尿1例,经对症处理好转.在随访过程中,发生糖尿病共3例,试验组1例,对照组2例.结论 在肾移植术后早期对肾功能稳定的患者进行SRL替代CNI能进一步显著改善肾功能,随访期间急性排斥反应无增加,切换后血脂升高明显但容易控制,余未见其他明显毒副作用.

Objective To explore the efficacy and safety of designed early conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) as major immunosuppressive therapy in renal transplant recipients with stable renal function.Methods A prospective,open-label and non-randomized control study was performed for 112 renal transplant recipients (3-6 months post-operation) with stable renal function between June 2008 and June 2011.The patients in SRL group (n =57) switched to sirolimus while those in CNI group (n =55) continued CNI.The dosing of mycophenolate mofetil and steroids had no change.They were followed up for at least 24 months to evaluate the acute rejection,patient and graft survival,renal function,estimated glomerular filtration rate (eGFR),blood lipids,blood glucose,liver function and urinary protein at 1,6,12 and 24 months after inclusion.Adverse events were also recorded.Results The serum creatinine of SRL group decreased significantly after conversion ((89.2 ± 24.7),(87.6 ± 23.8),(86.1 ±20.4),(86.7 ± 19.7) vs(117.0 ± 16.3) μ.mol/L,all P ＜ 0.05).CNI group showed no improvement of renal function.SRL group had a significantly higher eGFR than CNI group (P ＜ 0.05).Among 3 cases of acute rejection,there were 2 in SRL group and 1 in CNI group (P ＞ 0.05).Blood lipids in SRL group increased significantly at 1 month after conversion (P ＜ 0.05) and reverted back to average level after intervention (P ＞ 0.05).SRL group had a drop of hemoglobin level within the normal range.Two patients in SRL group developed hypokalemia and another 2 patients had oral ulcer.They all improved after treatment.During follow-ups,1 case of mild proteinuria was found in SIR group.Three patients were diagnosed with diabetes (1 in SRL group vs 2 in CNI group).Conclusions Early conversion from CNI to SRL as major immunosuppressive therapy in renal transplant recipients with stable renal function further improves renal function.There is no higher rate of acute rejection during follow-up.Elevated blood lipids after conversion may be easily controlled.No other adverse events are found.