Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Aug 6;2(3):56-76.
doi: 10.5527/wjn.v2.i3.56.

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Maurizio Salvadori  1 , Elisabetta Bertoni
Affiliations
Review

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Maurizio Salvadori et al. World J Nephrol. .

Abstract

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

PubMed Disclaimer

Figures

Figure 1
Figure 1
Pathogenetic mechanisms of thrombotic microangiopathy. MCP: Membrane cofactor protein.
Figure 2
Figure 2
Diagnostic algorithm to distinguish among different Hemolytic uremic syndrome. HUS: Hemolytic uremic syndrome; E. coli: Escherichia coli.
Figure 3
Figure 3
Alternative pathway. The alternative pathway is triggered by spontaneous activation of C3. Activation of this pathway leads to MAC formation which results in cell lysis (in red complement regulatory proteins; in black complement activating factors). CFH: Complement factor H; CFI: Complement factor I; DAF: Decay accelerating factor; MAC: Membrane attack complex; MCP: Membrane cofactor protein; THBD: Thrombomodulin.
Figure 4
Figure 4
Complement regulatory factors. CR1: Complement receptor 1; DAF: Decay-accelerating factor; MCP: Membrane cofactor of proteolysis.
See this image and copyright information in PMC

References

    1. Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia. Schweiz Med Wochenschr. 1955;85:905–909. - PubMed
    1. Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int. 2006;70:423–431. - PubMed
    1. Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012;8:622–633. - PubMed
    1. Liu J, Hutzler M, Li C, Pechet L. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS): the new thinking. J Thromb Thrombolysis. 2001;11:261–272. - PubMed
    1. Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis. 1985;151:775–782. - PubMed