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Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome

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Abstract

Shiga toxin-associated haemolytic uraemic syndrome (Stx HUS) is the leading cause of paediatric acute kidney injury. This toxin-mediated disease carries a significant morbidity and mortality but has no direct treatments. Rare familial atypical HUS (aHUS) is now understood to result from over-activation of the alternative complement pathway causing glomerular endothelial damage. By understanding the pathogenic mechanisms of this disease, the monoclonal antibody eculizumab, which blocks the final common pathway of complement, is now being used to treat aHUS. For this reason, clinicians and scientists are studying the role of the alternative complement pathway in Stx HUS with the aim of targeting treatment in a similar way. There is some evidence suggesting that complement plays a role in the pathogenesis of Stx HUS, but other mechanisms may also be important. Clinically, modulating the complement system using plasma exchange provides no proven benefit in Stx HUS, and the use of eculizumab has provided conflicting results. Understanding the local effect of Stx on the glomerulus, in particular regulation of the complement and coagulation systems, may lead to advances in defining the precise pathogenesis of this disease. Then, targeted treatment strategies could be devised and clinical trials undertaken.

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Acknowledgements

Dr. Lindsay Keir is supported by a British Medical Research Council Clinical Research Training Fellowship (Grant No. G0901987).

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  1. Academic Renal Unit, University of Bristol–Southmead Hospital, Bristol, UK

    Lindsay S. Keir & Moin A. Saleem

  2. Children’s Renal Unit, University of Bristol–Bristol Royal Hospital for Children, Bristol, UK

    Moin A. Saleem

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Keir, L.S., Saleem, M.A. Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome. Pediatr Nephrol 29, 1895–1902 (2014). https://doi.org/10.1007/s00467-013-2561-1

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