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Review
. 2014 May;3(2):34-45.
doi: 10.5582/irdr.2014.01001.

Current treatment of atypical hemolytic uremic syndrome

Bernard S Kaplan  1 , Rebecca L Ruebner  1 , Joann M Spinale  1 , Lawrence Copelovitch  1
Affiliations
Review

Current treatment of atypical hemolytic uremic syndrome

Bernard S Kaplan et al. Intractable Rare Dis Res. 2014 May.

Abstract

Tremendous advances have been made in understanding the pathogenesis of atypical Hemolytic Uremic Syndrome (aHUS), an extremely rare disease. Insights into the molecular biology of aHUS resulted in rapid advances in treatment with eculizumab (Soliris(®), Alexion Pharmaceuticals Inc.). Historically, aHUS was associated with very high rates of mortality and morbidity. Prior therapies included plasma therapy and/or liver transplantation. Although often life saving, these were imperfect and had many complications. We review the conditions included under the rubric of aHUS: S. pneumoniae HUS (SpHUS), inborn errors of metabolism, and disorders of complement regulation, emphasizing their differences and similarities. We focus on the clinical features, diagnosis, and pathogenesis, and treatment of aHUS that results from mutations in genes encoding alternative complement regulators, SpHUS and HUS associated with inborn errors of metabolism. Mutations in complement genes, or antibodies to their protein products, result in unregulated activity of the alternate complement pathway, endothelial injury, and thrombotic microangiopathy (TMA). Eculizumab is a humanized monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex (C5b-9) by binding to complement protein C5a. This blocks the proinflammatory and cytolytic effects of terminal complement activation. Eculizumab use has been reported in many case reports, and retrospective and prospective clinical trials in aHUS. There have been few serious side effects and no reports of tachphylaxis or drug resistance. The results are very encouraging and eculizumab is now recognized as the treatment of choice for aHUS.

Keywords: Alternate pathway of complement; Cbl deficiency; DGPE deficiency; S. pneumoniae hemolytic uremic syndrome; atypical hemolytic uremic syndrome; eculizumab; hemolytic uremic syndrome; thrombotic microangiopathy.

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References

    1. Kaplan BS, Drummond KN. The hemolytic-uremic syndrome is a syndrome. N Engl J Med. 1978; 298:964-966 - PubMed
    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 (in German) - PubMed
    1. Barnard PJ, Kibel M. The haemolytic-uraemic syndrome of infancy and childhood. A report of eleven cases. Cent Afr J Med. 1965; 11:31-34 - PubMed
    1. Zheng XL, Wu HM, Shang D, Falls E, Skipwith CG, Cataland SR, Bennett CL, Kwaan HC. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura. Haematologica. 2010; 95:1555-1562 - PMC - PubMed
    1. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014;164: 759-766 - PMC - PubMed

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