Studies on the Pathogenesis of Steroidnephropathy

Abstract

Forty rabbits were injected with 20 mg of prednisolone intramuscularly daily and sacrificed at 2, 5, 11, 24, 42 and 91 days by air-infusion. Kidneys were investigated by histochemical, immunofluo-rescent, light and electron-miroscopic methods. Urinary findings, blood coagulations, plasma lipids, plasma total protein and blood sugar levels were determined serially. The platelet aggregation as well as the plasma recalcification time reduced markedly from 2 to 42' days after starting-injections. Thrombotest activities already markedly increased on the 12th hour, and these conditions persisted during the treatment. Increases with transitory falls of platelet counts and plasma fibrinogen concentrations, accompanying suppressions or activations of fibrinolysis were observed. We thought that these findings of blood coagulations represented essentially a hypercoagulable state and both transitory falls of platelet counts as well as plasma fibrinogen concentrations and activations of fibrinolysis suggested slight intravascular coagulation with increased utilization of clotting factors such as platelets and fibrinogen, as well as secondary activation of fibrinolysis. In plasma lipids, only triglyceride levels increased significantly and directly proportional to the number of glomerulus affected with the lesions. Levels of fasting blood sugar almost unchanged except those of 42 nd day. In urinalysis, proteinuria, occasionally with hematuria began to appear early and increased gradually in quantity showing several peaks. Glycosuria appeared transitory early, became persistent in the latter part of the experimental period. Morphologically, the exudative lesions with various quantities of fibrin or fibrinoid, plasma protein, inucopolysaccharides, lipids, hyaline-material, blood corpuscles and degenerated constituents of capillary wall, intracapillary microthrombi and focal capillary dilatations were noticed in renal glomeruli. Lesions observed at 2nd and 5th days were composed of fresh, eosinophilic exudations but lesions after 11 st day chiefly of so-called exudative ones. Healing processes of those were observed at 42 nd and 91 st days. Incidences of the lesions gradually increased with times of injection repeated. Immunofluorescent studies for IgG, alc-globulin, fibrinogen and platelet deposits revealed localizations of those in exudative and other minimal glomerular lesions. The fluorescence of these two were more striking than others generally. When viewed in electronmicoscope, the exudative lesions were found to be composed principally of an intraluminal mass of fine-fibrillar substance. Besides, same substances appeared in mesangial matrixx and epithelial cytoplasm, and communicated with the intraluminal one. Conclusions are as follows : 1) Thrombocapillaropathy initiated by intracapillary microthrombi of glomeruli is an essential process in steroidnephropathy, 2) Formations and resolutions of the exudative lesion are repeated during the administration of glucocorticoids.