T. Arai et al., ULTRASTRUCTURAL BACKGROUND OF ALBUMINURIA IN RATS WITH PASSIVE HEYMANN NEPHRITIS, Nephrology, dialysis, transplantation, 12(12), 1997, pp. 2542-2548
Background. Although it is widely known that proteinuria in rats with
passive Heymann nephritis (PHN) is prevented by treatment with cobra v
enom factor (CVF), the precise mechanisms of complement-dependent prot
einuria have not been fully elucidated. The aim of this study was to e
valuate morphologically whether the size of subepithelial electron-den
se deposits (EDDs) contributes to the onset of albuminuria. Methods, T
he size of subepithelial EDDs and anionic sites in the lamina rarae ex
terna (LRE) overlaid with subepithelial EDDs were evaluated by rutheni
um red and compared between PHN and PHN treated with CVF in rats. Resu
lts, Overt albuminuria was present on days 3 and 4 after injection of
anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN+C
VF: 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 pos
t-injection in rats with PHN, but not in rats with PHN + CVF. Subepith
elial EDDs were observed in both groups. Quantitative morphometric ana
lysis revealed that CVF-treatment decreased the size of subepithelial
EDDs as well as the extent of retraction of glomerular epithelial cell
s. In both groups the density of anionic sites in the LRE overlaid wit
h 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 onse
t of albuminuria.