Nephrology Dialysis Transplantation, Vol 12, Issue 12 2542-2548, Copyright © 1997 by Oxford University Press
T Arai, K Morimoto, H Masaoka, O Kaneko, J Mera, K Kojima, M Nagase, S Kobayashi, T Ohtake and A Hishida
Background: Although it is widely known that
proteinuria in rats with passive Heymann nephritis (PHN) is prevented by
treatment wit cobra venom factor (CVF), the precise mechanisms of
complement-dependent proteinuria have not been fully elucidated. The aim of
this study was to evaluate morphologically whether the size of
subepithelial electron-dense deposits (EDDs) contributes to the onset of
albuminuria. Methods: The size of subepithelial EDDs
and anionic sites in the lamina rarae externa (LRE) overlaid with
subepithelial EDDs were evaluated by ruthenium red and compared between PHN
and PHN treated with CVF in rats. Results: Overt
albuminuria was present on days 3 and 4 after injection of anti-Fx1A.
CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n=6)
53.6±38.8 vs 1.02±0.55 mg/day, P
<0.01, on day 4). Rat C3 was detected along the glomerular capillary
walls on day 4 post-injection in rats with PHN but not in rats with PHN +
CVF. Subepithelial EDDs were observed in both groups. Quantitative
morphometric analysis revealed that CVF-treatment decreased the size of
subepithelial EDDs as well as the extent of retraction of glomerular
epithelial cells. In both groups the density of anionic sites in the LRE
overlaid with EDDs was decreased compared with the LRE without
subepithelial EDDs. However no difference was noted between the two groups.
Conclusion: Depletion of serum complement decreases
subepithelial EDDs as well as the number of sites with decreased anionic
charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a
pivotal role in the onset of albuminuria. Key words:
albuminuria; anionic sites; complement; electron-dense deposit; passive
Heymann nephritis
ORIGINAL ARTICLES
Ultrastructural background of albuminuria in rats with passive Heymann nephritis
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Division of Electron Microscopy, University Hospital, Mizonokuchi, Teikyo University School of Medicine, Takatsuku, Kawasakisi, Japan; Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashiku, Tokyo 173 Japan; Corresponding author
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