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 inves- tigation 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

expres- sions 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 urine TGF-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 concentration was 273.8 ± 84.1 pg/mg·Cr in group A and 457.2 ± 78.9 pg/mg·Cr in group B. During one year study period

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-beta1 may play a decisive role in the efficacy of losartan.