[Potassium hydrogen phosphate induced nephropathy in the dog. II. Glomerular alterations (author's transl)].

A disseminated atrophy of the proximal tubule accompanies K2HPO4-induced nephropathy in dogs. These pathologic processes cause glomerular changes that pass through different inflammatory stages and terminate in glomerular sclerosis. Experimental animals, design of the experiment and methods have been described [15]. During the 14-week study we determined the amount of urine (24 hours), protein (mg/dl), protein excretion (mg protein/24 hr) and the macro- and microprotein fraction in the urine by SDS-polyacrylamide gel electrophoresis. Clinical examinations were at 15, 66, and 85 days. Beagle dogs treated with 0.8 g K2HPO4/kg body weight developed significant glomerular selective and unselective protienuria. During the experiment the macroproteins in the urine decreased markedly, and at the last examination (day 85) glomerular proteinuria was no longer detectable by electrophoresis. Morphologically, there were only slight glomerular changes in the biopsy material taken at four weeks. Widespread lesions at 14 and 38 weeks were dilatation of Bowman's space, thickening of the basement membrane, increase in mesangial matrix, interposition of non-argentophilic mesangial matrix into the glomerular basement membrane, protein deposits in the mesangium and parietal basement membrane, formation of crescents, shrinkage of the glomeruli with collapse of glomerular tufts, and finally glomerular sclerosis. The parietal epithelial cells contained cytoplasmic areas that were free of organelles and contained microfilamentous and fine-granular material. These areas were close to the capsular basement membrane. Bundles of filaments within parietal epithelial cells had contact with the basement membrane, thus resembling hemidesmosomes. The sequelae of tubular atrophy are retention of glomerular filtrate and dilatation of Bowman's space, followed by compression and shrinkage of the glomerular tufts, and inflammatory processes within the glomerulus. The latter may be characterized as mesangio-sclerosing, mesangio-proliferative, membrano-proliferative, and extra-capillary glomerulonephritis. The decrease of urinary protein excretion towards the end of the experiment may be related to intratubular lysosomal digestion of cellular and amorphous components.