血管紧张素Ⅱ受体拮抗剂延缓慢性移植肾肾病肾功能损害的临床研究

Clinical study of effect of losartan on renal function in patients with chronic allograft nephropathy

目的探讨血管紧张素Ⅱ受体拮抗剂洛沙坦能否延缓慢性移植肾肾病(CAN)肾功能衰退的进程及其机理。方法对病理诊断为CAN(Ⅰ级)肾功能不全的22例肾移植患者(A组)使用洛沙坦治疗1年以上,与同期未使用洛沙坦的24例CAN(Ⅰ级)患者(B组)进行对比,比较2组1年后肾功能、尿TGF-β1浓度;并比较A组患者治疗前后移植肾活检组织中TGF-β1mRNA的表达量和TGF-β1免疫荧光强度等。结果1年后,A组肾功能稳定12例、好转2例,而B组肾功能稳定4例,其他患者肾功能均进行性恶化,2组差异有统计学意义(P<0.01)。A组服用洛沙坦1年后,尿TGF-β1浓度为(273.8±84.1)pg/mg.Cr,明显低于B组(457.2±78.9)pg/mg.Cr(P<0.01);A、B 2组肌酐清除率(Ccr)减损量分别为(6.6±5.4)、(16.2±9.1)m l/m in(P<0.01)。A组服药后肾组织中TGF-β1mRNA表达量由1.58±0.36降为0.96±0.27,TGF-β1免疫荧光强度由(10.83±2.33)×106降为(6.41±1.53)×106,差异均有统计学意义(P<0.01)。使用洛沙坦无不良反应发生。结论洛沙坦对CAN(I级)患者肾功能损害具有延缓作用,其机理可能与降低移植肾内TGF-β1的分泌有关。

Objective To determine the efficacy of losartan,a specific angiotensin Ⅱ receptor antagonist ,in slowing progression of renal insufficiency in patients with biopsy-proven chronic allograft nephropathy （CAN） and the molecular mechanism of the therapy. Methods Twenty-two renal transplant recipients with CAN （group A ） were treated with losartan for at least 1 year;and 24 patients with CAN （group B） without treatment of losartan served as controls during the same period. Renal function and urine TGF-β1, concentration were compared between the 2 groups. In group A,expression of TGF-β1 mRNA and intensity of ＂TGF-β1 immunofluorescence in renal allograft biopsy tissue were compared between before and 1 year after use of losartan, Results After 1 year,allograft function were stabilized in 12 patients,improved in 2 and .progressively worsen in 8 in group A;while in group B,allograft function was stabilized in only 4 patients and was progressively worsen in the rest 20 patients. There was significant difference between the 2 groups （P 〈 0.01 ）. The urine TGF-β1, concentrations of groups A and B were （273.8 ± 84.1 ） pg/mg · Cr and （457.2± 78.9） pg/mg · Cr,respectively, with significant difference between them （P 〈 0.01 ）. The losses of creatinine elearance of groups A and B were （6.6 ±5.a） ml/min and （16.2±9.1）ml/min （P〈0.01）,In group A, there was significant decrease in expression of TGF-β1 mRNA （from 1.58 ± 0.36 to 0.96 ± 0. 27 ） and intensity of TGF-β1 immunofluorescence [ from （ 10.83±2.33 ） × 10^6 to （6.41 ± 1.53） × 10^6 ] 1 year after use of losartan （P 〈 0.01 ）. No side effects were found in all the patients in group A. Conclusions This study suggests that losartan has an effect in slowing the progression of CAN. Reducing production of intrarenal TGF-β1 by losartan may play a decisive role in this mechanism.