The role of fibrinogen in renal disease. III. Fibrinolytic and anticoagulant treatment of nephrotoxic serum nephritis in mice

Nephrotoxic serum nephritis was induced in mice by rabbit antiserum. The natural history of the lesion was observed for periods up to 30 days. Basement membrane thickening occurred with only minimal endothelial cell proliferation. Glomerular obsolescence with capsular proliferation was found at 30 days. Immunofluorescent studies showed deposition of rabbit gamma globulin, mouse gamma globulin, and mouse complement along the basement membranes, while mouse fibrinogen or fibrin was deposited more diffusely within endothelial and mesangial cells as well as along the basement membranes. Fibrinolytic therapy with urokinase decreased the fibrinogen or fibrin in glomeruli but did not lessen proteinuria or progressive thickening of the glomerular basement membranes. Heparin neither reduced fibrinogen or fibrin deposition nor improved the histological appearance. We conclude that while fibrinogen or fibrin deposition plays an important role in the endothelial cell proliferation and crescent formation characteristic of proliferative types of glomerulonephritis, as shown in other studies, it is not a primary mediator in the pathogenesis of the membranous lesions of nephrotoxic serum nephritis in the mouse.