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World J Nephrol. Aug 6, 2013; 2(3): 56-76
Published online Aug 6, 2013. doi: 10.5527/wjn.v2.i3.56
Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations
Maurizio Salvadori, Elisabetta Bertoni
Maurizio Salvadori, Elisabetta Bertoni, Renal Unit, Careggi Hospital, Careggi University, Florence 50139, Italy
Author contributions: Salvadori M and Bertoni E equally contributed to writing the paper, collecting the literature data, revising both the scientific contents and the English wording, and gave the final approval of the version to be published.
Correspondence to: Maurizio Salvadori, MD, Professor, Renal Unit, Careggi Hospital, Careggi University, Viale Pieraccini 18, Florence 50139, Italy.
Telephone: +39-55-7949269 Fax: +39-55-435878
Received: May 7, 2013
Revised: June 26, 2013
Accepted: August 2, 2013
Published online: August 6, 2013

Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both “traditional therapy” (including plasma therapy, kidney and kidney-liver transplantation) and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases I and II. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.

Keywords: Enterohemorrhagic Escherichia coli, Diarrhea, Shiga toxin (Stx) 1 and Stx 2, Atypical hemolytic uremic syndrome, Complement factors, Thrombotic thrombocytopenic purpura, Secondary thrombotic microangiopathy, Plasma therapy, Eculizumab

Core tip: Hemolytic uremic syndrome (HUS) is a rare disease, knowledge of which is rapidly increasing. The disease takes several forms, but recent data suggest that the physiopathologic basis in the vast majority of such diseases is complement dysregulation. New therapies are available, including a monoclonal antibody that blocks the C5 cascade. Such therapies lead to a substantial improvement in the outcome, which previously was often poor. HUS often occurs secondary to other diseases. In such cases, diagnosis may be difficult due to the overlapping of two diseases. Complement dysregulation has been found also in secondary HUS.