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.
Ishikawa
A
A
Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. ishikawaa-uro@h.u-tokyo.ac.jp
Tanaka
M
M
Ohta
N
N
Ozono
S
S
Kitamura
T
T
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000473:pathology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*
D047228:Angiotensin II Type 1 Receptor Blockers; D007166:Immunosuppressive Agents; D000804:Angiotensin II; D016572:Cyclosporine; D019808:Losartan