The relationship between
proteinuria and
glomerular polyanion (GPA) charge has been studied in a model of experimental
cadmium (Cd) nephropathy. Female Sprague-Dawley rats were administered Cd in
drinking water for up to 18 months. From month 2, the animals showed an elevation of
albuminuria preceding by about 6 months the rise of urinary
beta 2-microglobulin and
IgG. The nephrotoxic action of Cd was not readily detectable on the basis of the urinary output of
beta-N-acetylglucosaminidase,
alanine aminopeptidase and
lactate dehydrogenase. These
enzymes showed either little variation or were affected late in the intoxication process. Administration of Cd for 12 or 18 months did not impair the GFR. The glomerular origin of the
albuminuria induced by Cd was demonstrated by estimating the glomerular filtration of rat or human (injected intravenously)
albumin in rats whose tubular reabsorption had been blocked by a saturating dose of
cytochrome C. The GPA charge was assessed by measuring the binding of the cationic
dye,
Alcian blue (AB), to membranes of isolated glomeruli. The sialic and
sulfate content of these membranes was also determined. The Cd induced-
albuminuria was negatively correlated (r = -0.73; n = 37) with the AB binding to glomerular membranes, their
sialic acid content (r = -0.39) but not with their
sulfate content (r = -0.15). A negative correlation (r = -0.62; n = 37) was also observed between the
albuminuria and red blood cell membrane negative charges largely contributed by
sialic acid. All these observations can be interpreted as the evidence that Cd enhances the glomerular filtration of
proteins through a GPA depletion involving mainly
sialic acid.