Studies on the Pathogenesis of Experimental Steroid Nephropathy

V. Serial Light, Electron Microscopic and Immunofluorescent Observations

Abstract

Thirty-four rabbits were given 20 mg of prednisolone intramuscularly daily and sacrificed at 2, 5, , 11, 24, 42 and 91 days by air-infusion. Kidneys were investigated by histochemistry, immunofluores cent studies and electronmicroscopy. Results were as follows: 1) In glomeruli, fresh exudations, so-called exudative lesions, intracapillary microthrombi and focal capillary dilatations were noticed. Lesions observed at 2 and 5 days were composed of fresh, eosinophilic exudations but lesions from 11 days to 91 days chiefly of eosinophilic, finely granular or fibrillar, exudative ones. Healing processes of those were observed at 42 and 91 days. Incidences of these lesions gradually increased with times of injec-tion. Histochemical studies showed that exudative lesions contained various quantities of fibrin or fib-rinoid, plasma protein, mucopolysaccharide, lipid and hyaline material. 2) Immunofluorescent studies for IgG, beta 1c-globulin, fibrinogen and platelet depositions revealed localizations of those in exudative and other minimal glomerular lesions. The fluorescence of these two were more striking than others generally. 3) When viewed in the electronmicroscope, exudative lesions were found to be composedd principally of an intra-luminal mass of amorphous debris, almost of it posessing a fine-fibrillar quality. The capillary walls surrounding these lesions displayed various changes ; absence of endothelial cells and foot processes, destruction of the basement membrane, and mesangial swelling, etc. In mesangial matrix and epithelial cytoplasm, the electron-dense, fibrillar substances appeared andd communicated with the intraluminal same ones. Conclusions are as follows: 1) Thrombocapillaropathy induced by intracapillary microthrombi of glomeruli is an essential process in the pathogenesis of steroidnephropathy. 2) Gradually increasedd incidences of exudative lesions during observation, and the coexistence of healing processes, so-calledd exudative lesions and fresh exudations in 42 and 91 days-groups suggest that these lesions are formed repeatedly during prednisolone administration.