title: Renal and neurological involvement in typical Shiga toxin-associated HUS.
abstract: Shiga toxin-producing Escherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is one of the most important causes of acute kidney injury in patients of all ages, especially in children. It can occur sporadically or in outbreaks. STEC-HUS is a systemic illness caused by toxin-mediated injury to the vascular endothelium and a generalized inflammatory response. The kidney and the brain are the two primary target organs. Nearly 40% of patients with STEC-HUS require at least temporary renal replacement therapy and up to 20% will have permanent residual kidney dysfunction. Neurological injury can be sudden and severe and is the most frequent cause of acute mortality in patients with STEC-HUS. Over the past 30 years, a wide range of inflammatory mediators have been linked to the pathogenesis of STEC-HUS and associated renal and neurological complications. Recently, evidence has accumulated that abnormal activation of the alternative pathway of complement occurs in patients with STEC-HUS. In the large outbreak of STEC-HUS caused by E. coli O104:H4 that occurred in Germany in May 2011, a large number of patients received eculizumab, a monoclonal antibody directed against C5, in an open-label manner. We describe the experience with eculizumab under these emergent circumstances at one large centre.
authors.affiliation: Department of Pediatrics, Division of Nephrology, NYU Langone Medical Center, Clinical Translational Science Institute, Room 712, 227 East 30th Street, New York, NY 10016-9196, USA. Trachtmanhoward.trachtman@nyumc.org
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: Catherine
authors.initials: C
authors.lastname: Austin
authors.forename: Maria
authors.initials: M
authors.lastname: Lewinski
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000382:microbiology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001921:Brain / Q000276:immunology / Q000382:microbiology; D001927:Brain Diseases / Q000382:microbiology; D015897:Comorbidity; D003167:Complement Activation; D003170:Complement Pathway, Alternative / Q000276:immunology; D004196:Disease Outbreaks; D005759:Gastroenteritis / Q000150:complications / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006463:Hemolytic-Uremic Syndrome / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000382:microbiology*; D009422:Nervous System Diseases / Q000382:microbiology*; D010951:Plasma Exchange; D017582:Renal Replacement Therapy; D054323:Shiga-Toxigenic Escherichia coli
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab