Hemolytic uremic syndrome (HUS) is a disease of non-immune hemolytic anemia, thrombocytopenia and renal failure due to platelet thrombi in the microcirculation of the kidney. It mainly affects infants and small children, though older children and adults may also suffer. The characteristic lesion, thrombotic microangiopathy (TMA)[1], is unique to this syndrome and consists of vessel wall thickening (capillaries and arterioles), with swelling and detachment of the endothelial cells from the base-ment membrane and accumulation of fluffy material in the subendothelium. Vascular lesions of HUS and of the related syndrome thrombotic thrombocytopenic purpura (TIP), a sys-temic form of TMA with neurological signs, are virtually identical and often indistinguishable from the microvascular lesions of scleroderma and malignant hypertension [2](Table 1). Typical HUS of children manifests with gastrointestinal (sometimes bloody diarrhea) or respiratory tract prodromes. In atypical and adult forms the disease may manifest with transient neurological signs secondary to platelet aggregation and obstruction of brain microcirculation. Endothelial dysfunction appears to be an impor-tant factor in the sequence of events leading to the microangiopathic process. Consistent with this interpretation are data that most agents associated with the disease, for example bacterial endotoxins, verotoxins, antibodies and immunocomplexes, and certain drugs, are toxic to endothelial cells.

Verotoxin-associated HUS In the last ten years the cause of gastrointestinal symptoms in HUS has been widely investigated. In the late 1970s Konowaichuk and coworkers [3] found that some strains of E. co/i produced certain exotoxins closely related to the 70 kDa protein encoded in Shigella dysenteriae DNA. The clinical significance of these toxins—Shiga-like toxins or verocytotoxins for their effect on kidney Vero cell lines—remained uncertain until 1983 when Riley et al [4] reported an association between E. co/i (serotype 0157: H7) infection and two outbreaks of hemorrhagic colitis, and Karmali et a![5] found verotoxin-producing E. co/i (VTEC) infection in 11 of 15 cases of sporadic HUS. It is now clear that VTEC is associated with a spectrum of illnesses that include asymptomatic infection, uncomplicated diarrhea, hemorrhagic colitis and HUS. Most information on VTEC is derived from study of the 0157: H7 serotype, easily distinguishable from other fecal E. co/i on account of its peculiar biochemical properties (lack of sorbitol fermentation). More information is now available on the non-0 157 serotypes and more than 50 different ones may cause the disease in humans. In 1983 a case-control study from the Centers for Disease