Is enalapril adequate for the prevention of renal tissue damage caused by unilateral ureteral obstruction and/or hyperoxaluria?
Unilateral ureteral obstruction (UUO) and hyperoxaluria (HOX) can lead to end-stage renal disease with tubulointerstitial fibrosis. We investigated the effects of enalapril (E), an ACE-inhibitor, on rat kidneys with either UUO or HOX. Sham-operated, UUO, HOX, UUO+HOX, UUO+E and HOX+E rats were killed 14 days after UUO and/or HOX was initiated. Rat kidney sections were histologically scored for tissue damage and monocyte/macrophage infiltration was demonstrated with ED1 antibody and measured by computer image analysis software. Serious glomerular and tubulointerstitial damage was found for UUO and HOX, consisting of glomerular basement membrane thickening, tubular dilatation/collapse, tubular basement membrane thickening and the infiltration of mononuclear leucocytes (mainly macrophages). For HOX, calcium oxalate crystals were visible. Neither the scored histological parameters nor monocyte/macrophage infiltration was significantly decreased when E-treated were compared with untreated groups. We conclude that E did not ameliorate the parameters scored in either UUO or HOX. This being contrary to findings by other research groups, we hypothesize that E may be effective only in short-term UUO/HOX, with transforming growth factor, TGF-beta1, formation becoming partly independent of Ang II in late-stage UUO/HOX, or other fibrogenic cytokines than TGF-beta1 becoming predominant.
Pediatric Urology, Erasmus Medical Center Rotterdam, The Netherlands.
T
T
Turan
J G
JG
van Harten
R
R
de Water
O L
OL
Tuncay
D J
DJ
Kok
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D053331:Ectodysplasins; D004656:Enalapril / Q000494:pharmacology*; D006959:Hyperoxaluria / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D053331:Ectodysplasins; D008565:Membrane Proteins; D004656:Enalapril