MECHANISMS OF GLOMERULAR INJURY - OVERVIEW AND RELATION WITH HEMOSTASIS

The mechanisms of glomerular injury can be separated into nonimmunolog ically mediated glomerulonephritis (GN) such as diabetes, leading to g lomerular hypertension and into immunologically mediated GN. The immun ologically mediated GN may induce chronic glomerulopathy such as membr anous GN or proliferative GN. The final pathway of these two types of GN is proteinuria and renal failure linked to glomerulosclerosis. In i nflammatory GN, most of the mediators could be synthesized either by i nfiltrating cells or by resident glomerular cells. They include cytoki nes, lymphokines, complement activation, generation of superoxyde anio ns, arachidonic acid metabolites, and fibrin deposition. (a) We have i nvestigated the interaction between isolated glomeruli and platelets a nd have demonstrated that lipidic and proteic extracts of glomeruli en hance thromboxane B2 platelet synthesis. This fact is related to the g eneration by isolated glomeruli of saturated fatty acids and tissue fa ctor. (b) We investigated the interaction between rat isolated glomeru li and peritoneal macrophages. We have demonstrated that 12-HETE synth esized by isolated glomeruli induce macrophage prostaglandin synthesis which, in turn, inhibits the 12-HETE synthesis. (c) We have demonstra ted, using human glomerular epithelial cells, that alpha-thrombin, the active form of thrombin, generated before fibrin formation, is able t o induce cell proliferation and abolishes the profibrinolytic activity of these cells. In summary, the mechanisms of glomerular injury are c omplex, certainly acting by multiple pathways. So far, the mediators l eading to proteinuria and renal failure after glomerular injury remain under investigation.