Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome

The aim of this review is to examine recent advances in experimental and cl inical research relevant to the pathogenesis of diarrhea-associated hemolyt ic uremic syndrome with special reference to histopathologic findings, viru lence factors of Shiga toxin-producing Escherichia coli, the host response, and the prothrombotic state. Despite significant advances during the past decade, the exact mechanism by-which Shiga toxin-producing E. coli leads to hemolytic uremic syndrome remains unclear. Factors such as Shiga toxin, li popolysaccharide, the adhesins intimin and E. coli-secreted proteins A, B, and D, the 60-MD plasmid, and enterohemolysin likely contribute to the path ogenesis. Data on the inflammatory response of the host, including leukocyt es and inflammatory mediators, are updated. The pathogenesis of the prothro mbotic state leading to thrombocytopenia secondary to endothelial cell dama ge and platelet activation is also discussed. A hypothetical sequence of ev ents from ingestion of the bacteria to the development of full-blown hemoly tic uremic syndrome is proposed.