血管紧张素转换酶抑制剂治疗慢性移植肾肾病的疗效观察

Clinical investigation of enalapril's effect on early chronic allograft nephropathy

目的:探讨血管紧张素转换酶抑制剂 (ACEI)依那普利 (enalapril)能否改善早期慢性移植肾肾病(CAN)患者的肾功能及其机制。 方法:对病理诊断为CANⅠ级的 23例患者(A组)于肾功能不全 2个月内开始服用依那普利(10mg/d),持续 1年以上,与同期内未服用ACEI的 25例CANⅠ级患者(B组)进行对比,比较两组患者 1年后肾功能、血和尿转化生长因子β1 (TGF β1 )水平(ELISA法测定);及治疗后移植肾组织中TGF β1mRNA表达量的变化(RT PCR法)。 结果:治疗 1年后,A组 15例(65 .2% )患者移植肾功能好转或稳定,B组中 4例(16. 0% )移植肾功能稳定,两组相比差异显著(P<0. 05)。观察终点时,A组肌酐清除率(Ccr)减损量[ (6 .6±5. 6 )vs(16 .3±9 .3)ml/min,P<0 01]、尿TGF β1 浓度(268 .2±82. 2vs458. 9±78 8pg/mg·Cr,P<0 .01)均明显低于B组;两组患者血TGF β1 浓度无明显差异。A组治疗后移植肾TGF β1mRNA表达量由 1 58±0 33降至 0 96±0 28(P<0 01)。 结论:依那普利能改善早期CAN患者的肾功能,抑制移植肾内TGF -β的表达。

Objective:The effects of rennin-angiotensin system have been implicated in the development of chronic allograf nephropathy. In this study, we investigated the effects of enalapril, an angiotensin converting enzyme inhibitor (ACEI), on protection of renal function in renal transplant recipients with biopsy proven early chronic allograft nephropathy (CAN, Grade I) and the molecular mechanism base underlying the effects of this agent. Methodology:48 renal transplant recipients were involved in this study. All of the patients met the diagnosis of CAN (grade I) after a renal allograft biopsy. Between September 2002 and November 2003, 23 of the 48 recipients (Group A)started enalapril treatment (at a dose of 10 mg/day) within 2 months after the establishment of renal dysfunction, and followed up for at least one year. Another 25 recipients with CAN (Group B) who never recieved ACEI treatment after the diagnosis were set up as the control at the same time. The investigation period for every patient lasted at least one year. Renal function, and the serum and urinary levels of transforming growth factor beta1 (TGF beta1) were determined at both the initiation and the end of the study. In group A, expressions of TGF beta1mRNA in renal biopsy specimens were examined before enalapril therapy and 1 year after the therapy. Results:At the initiation of the investigation, no significant differences were found between Group A and Group B in clinical data such as donor age, cold ischemia time, HLA mismatch, creatinine clearance rate (Ccr), blood and urine TGF beta1 concentrations ( P >0 05). One year after the treatment, 15 of 23 (65 2%) patients in Group A showed stable or improved graft functions, while only 4 of 25 (16 0%) in Group B, with a significance of difference ( P <0 05). At the end of the study, urinary TGF beta1 concentration was (268 2±82 2)pg/mg.Cr in Group A and (458 9±78 8)pg/mg.Cr in Group B( P <0 05). At the end of one year follow up, decrement of Ccr was (6 6±5 6)ml/min in Group A and (16 3±9 3) ml/min in Group B( P <0 05). No significant difference of in blood TGF beta1 concentrations was found after the treatment in both groups( P >0 05). A significant decrement in allograft TGF beta1mRNA expressions was found after 1 year enalapril therapy in Group A (pre treatment:1 58±0 33, and post treatment:0 96±0 28), while not in Group B (pre treatment: 1 58±0 37, and post treatment: 0 92±0 24). Enalapril was excellently tolerated in all the patients in group A without any side effect. Conclusion:This study suggests that enalapril have a protective effect in improving renal function in renal transplant recipients with chronic allograft nephropathy (Grade I). Decreased allograft TGF beta1 expression may be correlated to the efficacy of enalapril in this group of renal allograft recipients.