慢性移植肾肾病患者西罗莫司替代钙调磷酸酶抑制剂对肾功能的影响

目的 观察慢性移植肾肾病(CAN)患者采用西罗莫司(SIR)替代钙调磷酸酶抑制剂(CNI)治疗的疗效和安全性.方法 前瞻性、开放性、非随机对照研究,2004年1月至2006年6月浙江大学医学院附属第一医院肾脏病中心诊断CAN患者74例,基线估算的肾小球滤过率(eGFR)为30～60ml·min-1·(1.73 m2)-1.其中36例采用SIR切换治疗(CNI药物停用12 h后开始使用SIR),另外38例继续使用CNI药物维持治疗(环孢素治疗30例;他克莫司治疗8例).所有患者霉酚酸酯适当加量并随访4年,定期观察移植物肾功能和eGFR,记录排斥反应等不良事件的发生情况,监测血常规、血脂、肝功能等指标.结果 SIR切换组和CNI维持组切换前eGFR分别为(40±7)ml·min-1·(1.73 m2)-1和(38±6)ml· min-1· (1.73 m2)-1,差异无统计学意义(P＞0.05).切换后SIR切换组较CNI维持组移植肾功能改善明显,在随访至3、12、24、36和48个月时SIR切换组eGFR均明显高于CNI维持组(均P＜0.05).随访结束时SIR切换组发生急性排斥反应2例,蛋白尿1例,肺部感染1例;CNI维持组发生急性排斥反应2例(P＞0.05).以肌酐翻倍作为终点事件显示SIR切换组的4年存活率(75.0％)显著优于CNI维持组(50.0％)(P=0.03).随访3个月时SIR切换组血总胆固醇和甘油三酯均显著高于切换前;总胆红素显著低于切换前和CNI维持组(均P＜0.05).结论 SIR替代CNI药物治疗CAN患者可以明显改善移植肾肾功能,提高移植肾长期存活,同时并不增加排斥风险.

Conversion from calcineurin inhibitors to sirolimus in chronic allograft nephropathy: a 4-year prospective study

Objective To evaluate the safety and effect of sirolimus (SIR) substitution for calcineurin inhibitors (CNI) in chronic allograft nephropathy (CAN).Methods A prospective,open-label and non-randomized comparative study was performed in 74 kidney recipients from January 2004 to June 2006 with a diagnosis of CAN at a baseline estimated glomerular filtration rate ( eGFR ) of 30 - 60 ml · min-1 · ( 1.73 m2) -1.Patients in the SIR group (n =36) received SIR at 12 hours after a cessation of CNI.For those in the CNI group ( n =38 ),a cyclosporine (CsA) -based immunosuppressive regimen was prescribed in 30 patients and a tacrolimus ( FK506)-based regimen in another 8 patients.All patients were maintained under a high level of mycophenolate mofetil and followed up for 4 years to evaluate the renal function,eGFR,blood routines,blood lipids and liver function,etc. Results The renal function and eGFR profiles of the SIR group improved significantly after substitution.The baseline eGFR was (40 ± 7 ) ml · min - 1 · ( 1.73 m2 ) - 1 in the SIR group versus ( 38 ± 6 ) ml · min - 1 · ( 1.73 m2 ) - 1 in the CNI group (P ＞ 0.05).In SIR group,the levels of eGFR were higher than those in the CNI group at months 3,12,24,36 and 48 ( all P ＜ 0.05 ). For the endpoint of serum creatinine doubling,the 4-year survival was 75.0％ in the SIR group versus 50.0％ in the CNI group ( P =0.03 ). There were 2 cases of acute rejections,1 proteinuria,1 pneumonia in the SIR group while 2 patients in the CNI group dropped out as a result of acute rejections ( P ＞ 0.05 ).The total bilirubin value of all the patients decreased significantly but serum cholesterol and triglyceride levels increase significantly after conversion ( all P ＜ 0.05 ).Conclusion The substitution of SIR for CNI is both safe and effective in renal transplant recipients with CAN.And a conversion from CNI to SIR may improve the graft survival.