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Clinical practice

Today’s understanding of the haemolytic uraemic syndrome

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Abstract

The haemolytic uraemic syndrome (HUS) includes the triad of haemolytic anaemia, thrombocytopenia, and acute renal failure. The classical form [D(+) HUS] is caused by infectious agents, and it is a common cause of acute renal failure in children. The enterohaemorrhagic Escherichia coli-producing Shiga toxin (Stx) is the most common infectious agent causing HUS. Other infectious agents are Shigella and Streptococcus pneumoniae. Infections by S. pneumoniae can be particularly severe and has a higher acute mortality and a higher long-term morbidity compared to HUS by Stx. Atypical HUS [D(−)Stx(−)HUS] are often used by paediatricians to indicate a presentation of HUS without preceding diarrhoea. Almost all patients with D(−)Stx(−)HUS have a defect in the alternative pathway, for example, mutations in the genes for complement factor H, factor I, and membrane co-factor protein. Mutations in the factor H gene are described more often. The majority of children with D(+) HUS develop some degree of renal insufficiency, and approximately two thirds of children with HUS will require dialysis therapy, while about one third will have milder renal involvement without the need for dialysis therapy. General management of acute renal failure includes appropriate fluid and electrolyte management, antihypertensive therapy, and the initiation of renal replacement therapy when appropriate. Specific management issues in HUS include management of the haematological complications of HUS, monitoring for extra-renal involvement, avoiding antidiarrhoeal drugs, and possibly avoiding of antibiotic therapy. In addition to the obligatory supportive treatment and tight control of hypertension, there is anecdotal evidence that plasma therapy may induce remission and, in some cases, maintain it. Fresh frozen plasma contains factor H at physiological concentrations. A new therapy for D(−)Stx(−)HUS is a humanised monoclonal antibody (Eculizumab) that blocks complement activity by cleavage of the complement protein C5. It prevents the generation of the inflammatory peptide C5a and the cytotoxic membrane–attack complex C5b-9. We have first positive results, but it is still not approved for HUS.

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Correspondence to Lothar Bernd Zimmerhackl.

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Scheiring, J., Rosales, A. & Zimmerhackl, L.B. Clinical practice. Eur J Pediatr 169, 7–13 (2010). https://doi.org/10.1007/s00431-009-1039-4

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Keywords

  • Acute renal failure
  • Complement
  • Factor H
  • Transplantation
  • Dialysis
  • Streptococci
  • EHEC