Loss of glomerular polyanion correlated with albuminuria in experimental cadmium nephropathy.
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.
Bernard
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A
Unit of Industrial Toxicology and Occupational Medicine, Catholic University of Louvain, Clos Chapelle-aux-Champs, Brussels, Belgium.
Lauwerys
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R
Ouled Amor
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A
D000419:Albuminuria / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D002105:Cadmium Poisoning / Q000378:metabolism* / Q000652:urine; D004563:Electrochemistry; D004798:Enzymes / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000652:urine; D007678:Kidney Glomerulus / Q000378:metabolism*; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
D004798:Enzymes; D012795:Sialoglycoproteins; C001643:podocalyxin