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Chronic blockade of angiotensin II action prevents glomerulosclerosis, but induces graft vasculopathy in experimental kidney transplantation
Author(s) -
Smitvan Oosten Annemieke,
Navis Gerjan,
Stegeman Coen A.,
Joles Jaap A.,
Klok Pieter A.,
Kuipers Folkert,
Tiebosch Anton T. M. G.,
van Goor Harry
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(200105)194:1<122::aid-path859>3.0.co;2-t
Subject(s) - glomerulosclerosis , blockade , medicine , angiotensin ii , kidney transplantation , transplantation , renin–angiotensin system , kidney , urology , receptor , proteinuria , blood pressure
Long‐term renin–angiotensin system blockade is beneficial in a variety of renal diseases. This study examines the long‐term (34 weeks) effects of the angiotensin‐converting enzyme inhibitor lisinopril and the angiotensin II receptor type I blocker L158,809 in the Fisher to Lewis rat model of chronic renal transplant failure. Treatment in allografted rats with lisinopril or L158,809 was initiated 10 days after transplantation, or at the time when proteinuria exceeded 50 mg/24 h. Untreated allografts and syngrafts served as controls. In contrast to syngrafts, untreated allografts developed proteinuria, hypercholesterolaemia, interstitial damage, and glomerulosclerosis. Lisinopril or L158,809 treatment in allografts starting at day 10 after transplantation completely prevented this, with the exception of interstitial damage, but this treatment also caused a reduction in blood pressure and renal function. Moreover, the intimal surface area of the renal arteries was dramatically increased in allografts treated with either lisinopril or L158,809 compared with untreated allografted rats. Treatment once proteinuria had developed was less effective in preventing glomerulosclerosis, but also caused less intimal expansion. Thus, chronic renin–angiotensin system blockade preserves glomerular morphology in the absence of proteinuria, but enhances intimal hyperplasia and reduces renal function in experimental transplantation. In view of these results, it should be questioned whether such treatment benefits renal transplant patients in the long term. Copyright © 2001 John Wiley & Sons, Ltd.