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Objective To investigate the effects of losartan, a specific angiotensin Ⅱ receptor blocker, on 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 biopsy-proven CAN (group A) were treated with losartan within two months after renal dysfunction for at least one year. Losartan was administered at a dose of 50 mg/d. Twenty-four recipients in the same fashion (group B) who never received angiotensin Ⅱ receptor antagonist were studied as control. The investigation time for each patient lasted one year. Renal functions and concentrations of plasma and urine transforming growth factor-beta1 (TGF-beta1) were compared between the two groups at the initiation and end of the study. In group A, expressions of TGF-beta1 mRNA and immunofluorescence intensity of TGF-beta1 protein and pathological alterations in renal biopsy specimens were compared between before losartan therapy and after one year of 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, levels of creatinine clearance (Ccr), plasma and urineTGF-beta1 concentrations. One year later, 14 of 22 (63.6%) patients showed stable or improved graft functions in group A,and 4 of 24 (16.7%) in group B. The difference was significant (P＜0.05). At the end of the study, urine TGF-beta1 loss of Ccr was 6.6±5.4 mL/min in group A and 16.2±9.1 mL/min in group B. Both of the differences were significant between the two groups (P＜0.01). No significant differences were found in plasma TGF-beta1 concentrations between the four values determined at the initiation and end of the study in the two groups (F = 2.56, P ＞ 0.05). After one year losartan therapy, group A showed a significant decrease in expressions of TGF-beta1 mRNA and TGF-beta1 protein in renal biopsy specimens [from 1.59±0.35 to 0.96±0.27 and from (10.83 ± 2.33)×106 to (6.41±1.53)×106, respectively; both P＜0.01],but in light microscopy the histological changes were similar to the first renal biopsy. Losartan was excellently tolerated in all patients in group A. No cases with losartan therapy showed too low blood pressure and other side effects.Conclusion This study suggests that losartan have an effect on slowing progression of CAN. Reducing production of intrarenal TGF-betal may play a decisive role in the efficacy of losartan.