Hemolytic-Uremic Syndrome after Shigellosis: Relation to Endotoxemia and Circulating Immune Complexes

To investigate three possible causes of the acute hemolysis in the hemolytic-uremic syndrome, we studied prospectively 207 children and 34 adults with shigellosis in Bangladesh. Nineteen children showed acute hemolytic anemia, a leukemoid reaction, thrombocytopenia and oliguria; nine others had, in addition, a serum urea nitrogen level of over 100 mg per deciliter. Eight of the nine had pseudomembranous colitis, and six of the nine died. The frequency of bacteremia was similar in all grades of shigellosis. Circulating immune complexes were found in 10 of 20 patients with uncomplicated shigellosis and in four of six with severe hemolytic-uremic syndrome. Limulus assay for endotoxemia was positive in nine of 18 patients with hemolysis (50 per cent) and three of 61 with uncomplicated shigellosis (5 per cent) (P<0.001). These data support the hypothesis that severe colitis in shigellosis is associated with circulating endotoxin from the colon producing coagulopathy, renal microangiopathy and hemolytic anemia. (N Engl J Med 298:927–933, 1978) THE hemolytic-uremic syndrome was described by Gasser et al.¹ as the association of hemolytic anemia, thrombocytopenia and acute renal failure, and is one of the most common causes of acute renal failure in childhood in some regions of the world.² Observations that episodes of hemolysis with uremia occurred in clusters, were frequently preceded by bloody diarrhea and were associated with thrombotic renal microangiopathy¹ and mild disseminated intravascular coagulopathy² suggested that endotoxin, derived from the gastrointestinal tract, produced a Shwartzman-like reaction in the renal microvasculature.²³ However, clinical studies have failed to identify circulating endotoxin after the onset of renal failure⁴⁵ and.