Renal and neurological involvement in typical Shiga toxin-associated HUS

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.