ACE抑制剂预防CAN的临床研究

Angiotensin converting enzyme inhibitor administration for preventing CAN

目的:探讨血管紧张素转换酶(ACE)抑制剂依那普利(enalapril)对肾移植患者移植肾远期功能的保护作用。方法:2000年1月至2001年7月期间,对肾移植术后时间达1年、肾功正常、尿TGF-β1浓度≥250.0pg/mg.Cr的25例患者(A组)连续服用enalapril 1年以上,与同期内未服用enalapril的23例患者(B组)作对比,观察两组肾功能变化;3年后比较两组血和尿TGF-β1浓度、肌酐清除率(Ccr)减损量和肾功不全的病例数有无差异;比较A组服用enalapril前后,肾组织中TGF-β1表达量;观察服用enalapril的不良反应。结果:B组Ccr进行性降低,在3年随访期内,Ccr减损量为13.7±9.5(m l/m in),有9例(39.1%)肾功能不全,均明显大于A组(P<0.01、P<0.05);3年后尿TGF-β1浓度为507.7±53.1(pg/mg.Cr),明显大于A组(P<0.01),两组血TGF-β1浓度无明显差异;A组服用enalapril 1年后,肾组织中TGF-β1表达量显著降低,使用enalapril无不良反应。结论:enalapril对移植肾具有保护作用,其机制可能与降低肾内TGF-β1的分泌有关。

Objective： To observe whether enalapril, a specific angiotensin converting enzyme inhibitor, has a role in preventing chronic allograft nephropathy （CAN）. Methods： From January 1,2000 to July 30 twenty-five renal transplant recipients whose urine TGF-I31 concentration were higher than 250.0 pg/mg·Cr with normal renal function began angiotensin converting enzyme inhibitor（enalapril） therapy one year after surgery were studied as Group A. Each patient in Group A took 5mg enalapril every day for at least one year. Twenty-three recipients who never received angiotensin converting enzyme inhibitor were studied as Group B in the same fashion. Side-effects for takeing enalapril were investigated in all patients in Group A. intensions of TGF-β1 immunofluorescence in renal grafts were compared between before and 1 year after enalapril therapy in Group A. 3 years after initiation of enalapril, renal function and blood and urine TGF-β1 concentration were compared between the two groups. Results： Ccr decreased faster in Group B than Group A. Three years later, Ccr had been lost for 5.0±4.4 （ml/min） and there were 2 recepients with CAN in group A, but Group B had lost 13.7±9.5 （ml/min） in Ccr and showed 9 recepients with CAN. There were significantly more loss of renal function and more number of CAN cases in group B than group A. Urine TGF-β1 Ccr had Ccr had been lost for 5.0±4.4（ml/min） and there were 2 recepients with CAN in group A, but Group B had lost 13.7±9.5 （ml/min） in Ccr and showed 9 recepients with CAN. There were significantly more loss of renal function and more number of CAN cases in group B than group A. Urine TGF-β1 concentrations were 324.7±46.2 and 507.7±53.1 （pg/mg·Cr） in group A and B respectively 3 years after initiation of enalapril. It was significantly higher in group A than group B. The values of blood TGF-β1 concentration did not reveal any significant difference between the two groups. One year after enalapril therapy intensions of TGF-β1 immunofluorescence in Group A significantly decreased from 10.95±2.31 （×10^6 ） to 6.37±1.50 （×10^6 ）. No side-effects were noted in all patients who had taken enalapril. Conclusions： Enalapril can prevent chronic allograft nephropathy （CAN） in renal transplant recipients through reducing TGF-β1 secretion in the kidney.