环孢菌素A代以他克莫司延缓移植肾慢性失功临床研究  

Slowing progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus

作　　者：李风[1] 肖亚[2] 王平贤[2] 

机构地区：[1]重庆三峡中心医院泌尿外科,404000 [2]第三军医大学新桥医院,重庆400037

出　　处：《重庆医学》2009年第17期2139-2141,共3页Chongqing medicine

摘　　要：目的探讨他克莫司(FK506)替代环孢菌素A(CsA)延缓移植肾早期慢性肾功能衰竭的可行性。方法选取重庆三峡中心医院和重庆新桥医院2003年1月至2006年5月病理诊断为慢性移植肾肾病肾功能不全、且正在服用CsA的肾移植受者97例。随机将受者分为2个组:A组(50例)以FK506替换CsA,替换剂量比例约为1∶75,其他免疫抑制剂不变;B组(47例)则CsA和其他免疫抑制剂均不作调整。比较2个组受者3年后的肾功能、内生肌酐清除率(Ccr)减损量、血浆转化生长因子β1(TGF-β1)浓度和急性排斥反应发生率等。结果替换治疗3年后,A组有32例(64.0%)受者移植肾功能稳定或好转,而B组除4例(8.5%)肾功能稳定外,其他受者肾功能均进行性减退;A、B两组Ccr减损量分别为(0.169±0.153)mL/s和(0.378±0.291)mL/s;A、B两组血浆TGF-β1浓度分别为(17.4±8.9)μg/L和(39.5±11.5)μg/L。两组间各结果相比较,差异均有统计学意义(P<0.01)。两组急性排斥反应发生率分别为14.0%和12.8%,差异无统计学意义(P>0.05)。结论以FK506替代CsA可延缓慢性移植肾肾病受者肾功能衰竭的速度,其机制可能与抑制TGF-β1介导的移植肾纤维化有关。Objective To investigate the effects of substituting tacrolimus（FK506） for cyclosporine（CsA） on delaying the pace of renal dysfunction in the patients with biopsy-proven chronic allograft nephropathy（CAN） and the molecular mechanism of the therapy. Methods From January 1,2003 to May 31,2006,97 renal transplant recipients with declining graft function and biopsyproven CAN（grade I ） ,who had been taking cyclosporine（CsA） as immunosuppressive agent were studied. The patients were randomly divided into group A and group B. CsA was replaced with FK506 in group A including 50 patients. Group B including the other 47 patients was studied as control. Substituting CsA by FK506 in a dose of about 1 ： 75. All patients were followed up at least three years. Renal functions,losses of creatinine clearance rates within 3 years, incidences of acute renal graft rejection and plasma TGF-β1 concentrations were compared between the two groups. Results Three year later,there were 32 patients（64.0%） with stabilized or improved graft function in group A,and 4 patients（8.5%） in group B. The difference was significant（P〈0.01）. During the 3-year study period,loss of creatinine clearance in group A was （0. 169±0. 153）mL/s which was significantly more than （0. 378 ±0. 291）mL/s in group B（P〈0.01）. At the end of the study,plasma TGF-β1 concentration in group A was（17.4±8.9） ng/mL which was significantly lower than（39.5 ± 11. 5） ng/mL in group B（P〈 0.01）. The incidences of acute rejection in both groups were not significantly different. Conclusion This study suggests that in renal recipients with biopsy-proven CAN, substituting FK506 for CsA has an effect to slow progression of CAN. Reducing production of TGF-β1 may play a decisive role in the efficacy of the therapy.

关 键 词：移植 肾病 他克莫司 环孢菌素A 转化生长因子Β1 

分 类 号：R692[医药卫生—泌尿科学] R699.2[医药卫生—外科学]