Toxic glomerulosclerosis-morphology and pathogenesis. Light and electron microscopic studies fo the glomerular changes in the kidney of rats poisoned by N-nitrosomorpholine.

75 male rats were given toxic dosage of the hepatotoxin N-nitrosomorpholine (NNM) using varied concentrations over varied time intervals. During and after the toxic dosings the kidneys were examined by light and electron microscopy in order to decide, whether the kidneys are also damaged by NNM. Our studies reveal that under the influence of a low concentration of NNM a distinct thickening of the GBM and an increase of the mesangial matrix occurs (changes referred by us as glomerulosclerosis). When a high concentration of NNM was given, toxic lesions of the mesangial and epithelial cells of the glomeruli were found, but a glomerulosclerosis was not observed during the intoxication. After this toxic dose was stopped, however, a progressive glomerulosclerosis did develop, which at first was accompanied by a transient proliferation of the mesangial cells. The glomerular changes found in the course of poisoning with NNM were interpreted as a direct effect of the NNM. From studies of the formal pathogenesis of the glomerulosclerosis presented here one can conclude that the poisoning leads to a decrease in breakdown of the components of the basement membrane and the mesangial matrix, thus causing the widening of the GBM and the augmentation of the mesangial matrix.