CAJ | 학술논문

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.
목적 관찰만성이식신신병(CAN)환자채용서라막사(SIR)체대개조린산매억제제(CNI)치료적료효화안전성.방법 전첨성、개방성、비수궤대조연구,2004년1월지2006년6월절강대학의학원부속제일의원신장병중심진단CAN환자74례,기선고산적신소구려과솔(eGFR)위30～60ml·min-1·(1.73 m2)-1.기중36례채용SIR절환치료(CNI약물정용12 h후개시사용SIR),령외38례계속사용CNI약물유지치료(배포소치료30례；타극막사치료8례).소유환자매분산지괄당가량병수방4년,정기관찰이식물신공능화eGFR,기록배척반응등불량사건적발생정황,감측혈상규、혈지、간공능등지표.결과 SIR절환조화CNI유지조절환전eGFR분별위(40±7)ml·min-1·(1.73 m2)-1화(38±6)ml· min-1· (1.73 m2)-1,차이무통계학의의(P＞0.05).절환후SIR절환조교CNI유지조이식신공능개선명현,재수방지3、12、24、36화48개월시SIR절환조eGFR균명현고우CNI유지조(균P＜0.05).수방결속시SIR절환조발생급성배척반응2례,단백뇨1례,폐부감염1례；CNI유지조발생급성배척반응2례(P＞0.05).이기항번배작위종점사건현시SIR절환조적4년존활솔(75.0％)현저우우CNI유지조(50.0％)(P=0.03).수방3개월시SIR절환조혈총담고순화감유삼지균현저고우절환전；총담홍소현저저우절환전화CNI유지조(균P＜0.05).결론 SIR체대CNI약물치료CAN환자가이명현개선이식신신공능,제고이식신장기존활,동시병불증가배척풍험.
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.