Eculizumab in the treatment of Shiga toxin haemolytic uraemic syndrome

Pediatr Nephrol. 2019 Sep;34(9):1485-1492. doi: 10.1007/s00467-018-4025-0. Epub 2018 Jul 30.

Abstract

Haemolytic uraemic syndrome (HUS) remains a leading cause of paediatric acute kidney injury (AKI). Haemolytic uraemic syndrome is characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia and AKI. In ~ 90% of cases, HUS is a consequence of infection with Shiga toxin-producing E. coli (STEC), most commonly serotype O157:H7. Acute mortality from STEC-HUS is now less than 5%; however, there is significant long-term renal morbidity in one third of survivors. Currently, no specific treatment exists for STEC-HUS. There is growing interest in the role of complement in the pathogenesis of STEC-HUS due to the discovery of inherited and acquired dysregulation of the alternative complement system in the closely related disorder, atypical HUS (aHUS). The treatment of aHUS has been revolutionised by the introduction of the anti-C5 monoclonal antibody, eculizumab. However, the role of complement and anti-complement therapy in STEC-HUS remains unclear. Herein, we review the current evidence of the role of complement in STEC-HUS focusing on the use of eculizumab in this disease.

Keywords: Complement; Eculizumab; Haemolytic uraemic syndrome; STEC-HUS; Shiga toxin.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Complement Inactivating Agents / pharmacology
  • Complement Inactivating Agents / therapeutic use*
  • Complement Pathway, Alternative / drug effects
  • Complement Pathway, Alternative / immunology
  • Complement System Proteins / immunology*
  • Erythrocyte Transfusion
  • Hemolytic-Uremic Syndrome / immunology
  • Hemolytic-Uremic Syndrome / microbiology
  • Hemolytic-Uremic Syndrome / therapy*
  • Humans
  • Renal Dialysis
  • Shiga Toxin / immunology
  • Shiga-Toxigenic Escherichia coli / immunology
  • Shiga-Toxigenic Escherichia coli / isolation & purification*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • Shiga Toxin
  • Complement System Proteins
  • eculizumab