Prevention of interstitial fibrosis of renal allograft by angiotensin II blockade

We previously confirmed that losartan (LOS), an angiotensin-II (A-II) receptor blocker, diminished plasminogen activator inhibitor-1 (PAI-1) in cyclosporine (CsA)-treated renal graft recipients. Because PAI-1 is known to correlate with tissue fibrosis, we speculated that LOS would have the potential to prevent renal graft interstitial fibrosis. In this study, we focused our attention on the LOS-induced histopathologic changes in renal grafts. Out of 24 CsA-treated normotensive kidney transplanted patients, 8 began to take 25 to 50 mg/day of LOS soon after kidney transplantation (group 1). Eight did so 2 years after kidney transplantation (group 2). Eight received no ARBs as a control group (group 3). PAI-1 levels were monitored every 3 months for 2 years. Renal graft biopsy was performed on all participants, with informed consent, before and 2 years after the onset of this study. The biopsy specimens were stained with periodic acid-methenamine-silver (PAM)-Masson stain for light-microscopic examination. Fibrotic areas in each biopsy specimen were measured using the LUZEX-III image analyzing system. Statistical analysis was performed using Student's t-test. When we considered the pre-value of PAI-1 in each patient as 100%, the mean percent value of PAI-1 at 2 years after the onset of this study of groups 1, 2, and 3 were 81.5 +/- 10.3%, 90.1 +/- 12.5%, and 116.8 +/- 11.9%, respectively (P < .01 groups 1 and 2 vs group 3). Light-microscopic examination revealed less remarkable renal interstitial fibrosis among LOS administered groups. A-II blockade may be a key to prevent renal graft interstitial fibrosis.