Sequence of glomerular changes in experimental endotoxemia: a possible model of hemolytic uremic syndrome

Glomerular morphological changes produced by 5-hour intravenous infusion of endotoxin (40 micrograms/kg/h) were studied in 57 rabbits. During endotoxin infusion all animals developed signs of endotoxemia, anemia, and transient leukopenia and thrombocytopenia. Acute renal failure also developed in all animals. By light microscopy a marked polymorphonuclear cell infiltration was the prominent finding within 1 h from the beginning of the infusion. At hour 5 fibrin deposits and thrombi were detected in most animals. The abnormalities were reversible. By electron microscopy endothelial damage was detected few minutes after the beginning of endotoxin infusion followed by leukocyte and platelet infiltration in glomerular capillaries. Fibrin appeared at hour 5 as free strands into the lumens or in large clumps along the luminal surface of endothelial layer. Occasionally, occlusive fibrin thrombi were seen. At hour 48 only mild endothelial damage was seen, associated with few polymorphonuclear cells in the glomerular capillary lumens. These results document the sequence of renal changes in the best available animal model of hemolytic uremic syndrome. Beside endothelial damage, leukocyte infiltration in glomerular capillaries is a prominent finding suggesting a role of inflammatory cells in the development of microvascular thrombosis.