The pathophysiology of the hemolytic uremic syndrome.

The hemolytic uremic syndrome is an important cause of acute renal failure and leads to substantial morbidity and mortality. In pediatric patients, the hemolytic uremic syndrome usually follows hemorrhagic colitis caused by verocytotoxin-producing Escherichia coli. Several well-publicized outbreaks of hemorrhagic colitis and hemolytic uremic syndrome have highlighted the morbidity and mortality of infection with verocytotoxin-producing Escherichia coli. Recent studies have further demonstrated the role of verocytotoxins in mediating renal cell injury and the mechanisms of verocytotoxin cell injury. Although the endothelial cell appears to be the major target of verocytotoxin-mediated cell injury, studies have also shown that mesangial cells, renal tubular epithelial cells, monocytes and cells derived from the monocytic cell line are also targets of verocytotoxin-mediated biological effects. It has also been shown that inflammatory cytokines are likely to play an important role in hemolytic uremic syndrome. Serum levels of IL-8 and TNF-alpha are elevated in hemolytic uremic syndrome and verocytotoxins promote the generation of inflammatory cytokines from monocytes and monocyte-derived cell lines. These new findings have important implications for current therapy and potential future therapy of hemolytic uremic syndrome.