Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS)

Abstract

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood and the reason for chronic renal replacement therapy. It leads to significant morbidity and mortality during the acute phase. In addition to acute morbidity and mortality, long-term renal and extrarenal complications can occur in a substantial number of children years after the acute episode of HUS. The most common infectious agents causing HUS are enterohemorrhagic Escherichia coli (EHEC)-producing Shiga toxin (and belonging to the serotype O157:H7) and several non-O157:H7 serotypes. D(+) HUS is an acute disease characterized by prodromal diarrhea followed by acute renal failure. The classic clinical features of HUS include the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS mortality is reported to be between 3% and 5%, and death due to HUS is nearly always associated with severe extrarenal disease, including severe central nervous system (CNS) involvement. Approximately two thirds of children with HUS require dialysis therapy, and about one third have milder renal involvement without the need for dialysis therapy. General management of acute renal failure includes appropriate fluid and electrolyte management, antihypertensive therapy if necessary, and initiation of renal replacement therapy when appropriate. The prognosis of HUS depends on several contributing factors. In general "classic" HUS, induced by EHEC, has an overall better outcome. Totally different is the prognosis in patients with atypical and particularly recurrent HUS. However, patients with severe disease should be screened for genetic disorders of the complement system or other underlying diseases.

Fig. 1

Hematoxylin and eosin staining in hemolytic uremic syndrome (HUS). Note that two glomeruli are completely sclerosed (solid line). Mesangial expansion with beginning sclerosis in the third glomerulus (broken line). Focal inflammation in the tubular system indicating involution of renal parenchyma (arrow). Courtesy of Prof. Dr. Consolato Sergi

Fig. 2

Development of Shiga-toxin-associated hemolytic uremic syndrome (used with permission from [72])

Fig. 3

Pathophysiology of enterohemorrhagic Escherichia coli infection. Prodromal phase usually 3 days. Window for Shiga toxin antibody treatment is from day 0 to day 3 after onset of diarrhea. Sequelae in percent of patients. Adapted and modified from [24]