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Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies

Authors Keir, Marks S, Kim JJ

Received 18 April 2012

Accepted for publication 22 May 2012

Published 19 July 2012 Volume 2012:6 Pages 195—208

DOI https://doi.org/10.2147/DDDT.S25757

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Lindsay S Keir,1 Stephen D Marks,2 Jon Jin Kim2

1Academic Renal Unit, University of Bristol, Bristol; 2Department of Paediatric Nephrology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom

Abstract: 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.

Keywords: hemolytic uremic syndrome, shigatoxin, diarrhea, Escherichia coli, complement, alternative pathway, eculizumab

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