Intrarenal fibrin deposition and its relation to prognosis in proliferative glomerulonephritis.
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Biomedical subjects
Publications and source records attributed to M K MacDonald.
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Treatment with indomethacin, aspirin, or prednisone has been shown to reduce urinary fibrin/fibrinogen degradation products (F.D.P.) in approximately two-thirds of patients with proliferative glomerulonephritis. This reduction which is dose-dependent for prednisone but not for indomethacin or aspirin in the range of doses used occurs within two to three days of beginning treatment and is thought to result from decreased intraglomerular fibrin deposition rather than alteration of glomerular permeability to F.D.P. In patients who responded in this manner treatment was associated with reductions in the degree of proteinuria and maintenance or improvement in renal function.
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The possible role of fibrin deposition in the development of diabetic glomerulosclerosis has been investigated by light, immunofluorescence, and electron microscopy examination of renal tissue obtained by percutaneous biopsy from seven diabetic patients having minimal clinical evidence of renal involvement and at necropsy on nine diabetic patients. Although the biopsy specimens showed only early to moderate diffuse glomerulosclerosis without either nodular or exudative lesions, approximately 70% of glomeruli examined showed specific fluorescence for fibrinogen in a discontinuous linear pattern along the capillary basement membrane and diffusely in the mesangium. Moreover the immunofluorescence findings correlated well with the distribution patterns of material thought to be fibrin both in the light microscopy studies, by virtue of its staining properties, and by electron microscopy, because of periodicity, texture, and electron density. It is suggested that electron-dense granular deposits seen on electron microscopy may represent intermediate compounds in the fibrinogen to fibrin conversion, and that endothelial and mesangial trapping of fibrinogen or other macromolecules may initiate or accelerate mesangial enlargement, nodule formation, and irregularity of the basement membrane.
The serum and urine concentrations of fibrin/fibrinogen degradation products (F.D.P.) were estimated in 172 patients with glomerulonephritis. In each case the diagnosis was established on the basis of clinical, renal histological, and ultrastructural findings. Serum F.D.P. concentrations were often raised in all types of glomerulonephritis, though more consistently in active proliferative forms. The urinary concentration provided a reliable and sensitive index of activity, progression, and natural history in proliferative glomerulonephritis. In these forms the urinary F.D.P. content was thought to reflect predominantly lysis of intraglomerular fibrin deposits. In minimal lesion and membranous glomerulonephritis low but abnormal concentrations of urinary F.D.P. were consistently found. It is suggested that in these cases the products are derived from limited proteolysis of fibrinogen filtered through an abnormally permeable basement membrane.Daily measurement of urinary F.D.P. concentration is of potential value in the differential diagnosis of patients with glomerulonephritis and at the same time provides a sensitive assessment of the activity and natural history of proliferative disease.
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