普乐可复替换环孢素A减缓早期CAN肾功能减退  

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

作　　者：王平贤[1] 黄赤兵[1] 范明齐[1] 张艮甫[1] 

机构地区：[1]第三军医大学新桥医院泌尿外科,重庆400037

出　　处：《重庆医学》2006年第15期1358-1360,共3页Chongqing medicine

摘　　要：目的了解用普乐可复（FK506）替代环孢素A（CsA）能否减缓早期慢性移植肾肾病（CAN）患者肾功能衰竭的速度，及其机制。方法1999年1月-2003年4月期间，对病理诊断为慢性移植肾肾病（Ⅰ级）肾功不全、且正在服用CsA的124例肾移植患者随机分为A、B两组。A组（68例）：将CsA改为FK506，替换剂量比例约为75：1，其他免疫抑制剂不变；B组（56例）：环孢素A和其他免疫抑制剂均不作调整。对上述患者进行至少3年的随访，比较两组肾功能、3年随访期内肌酐清除率（Ccr）减损量、急性排斥反应发生率、血浆转移生长因子β1（TGF-β1）浓度等。结果3年后A组有42例（61．8％）患者移植肾功能稳定或好转，而B组除6例（10．7％）肾功能稳定外，其他患者肾功能均进行性减退；3年随访期内A、B两组Ccr分别减少了（10．1±9．9）ml／min和（22．3±16．7）ml／mim；3年后A、B两组血浆TGF-β1浓度分别为（16．7±8．7）ng／ml和（39．7±10．8）ng／ml。上述结果比较，两组差异有统计学意义（P〈0．01）。3年随访期内，两组急性排斥反应发生率分别为11．8％和10，7％，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患者肾功能衰竭的速度，其机制可能与降低体内TGF-β1分泌有关。Objective To investigate the effects of substituting tacrolimus （FKS06） for cyclosporine （CsA） on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy（CAN） and the molecular mechanism of the therapy. Methods From January 1, 1999 to April 30, 2003, 124 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 FKS06 in Group A that included 68 patients. Group B inclu- ding the other 56 patients was studied as control. Substituting CsA by FKS06 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 42 patients （61, 8 % ） with stabilized or improved graft function in Group A, and 6 patients （ 10.7 % % ） in Group B. The difference was significant （P〈0.01）. During the 3-year study period, loss of creatinine clearance in Group A was （10.1±9.9）ml/min which is signifi- cantly more than （22.3±16.7）ml/min in Group B （P〈0.01）. At the end of the study, plasma TGF-β1 concentration in Group A was （16.7±8.7）ng/ml which is significantly lower than （39.7± 10.8）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 have an effect to slow progression of CAN. Reducing production of TGF-betal may play a decisive role in the efficacy of the therapy.

关 键 词：肾移植 肾病 普乐可复 环孢素A 转移生长因子Β1 

分 类 号：R699.2[医药卫生—泌尿科学] R979.5[医药卫生—外科学]