Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies.
Hemolytic uremic syndrome is the leading cause of acute kidney injury in childhood. Ninety percent of cases are secondary to gastrointestinal infection with shigatoxin-producing bacteria. In this review, we discuss the molecular mechanisms of shigatoxin leading to hemolytic uremic syndrome and the emerging role of the complement system and vascular endothelial growth factor in its pathogenesis. We also review the evidence for treatment options to date, in particular antibiotics, plasma exchange, and immunoadsorption, and link this to the molecular pathology. Finally, we discuss future avenues of treatment, including shigatoxin-binding agents and complement inhibitors, such as eculizumab.
Academic Renal Unit, University of Bristol, Bristol, UK.
Lindsay S
LS
Keir
Stephen D
SD
Marks
Jon Jin
JJ
Kim
D058186:Acute Kidney Injury / Q000209:etiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications / Q000382:microbiology; D002648:Child; D005767:Gastrointestinal Diseases / Q000150:complications* / Q000382:microbiology; D006463:Hemolytic-Uremic Syndrome / Q000150:complications / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007163:Immunosorbent Techniques; D010951:Plasma Exchange / Q000379:methods; D022603:Shiga Toxins
D000900:Anti-Bacterial Agents; D061067:Antibodies, Monoclonal, Humanized; D022603:Shiga Toxins; C481642:eculizumab