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An international consensus approach to the management of atypical hemolytic uremic syndrome in children

Abstract

Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver–kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

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Acknowledgments

The authors wish to thank DR MK Taha, Institute Pasteur, Invasive Bacterial Infections Unit and National Reference Centre for Meningococci, Paris, France, for his helpful insights on the debate of meningococcal infection prophylaxis

Authors contribution

C. Loirat, F. Fakhouri and V. Fremeaux-Bacchi participated in the concept, design and writing of the article. C. Loirat, V. Fremeaux-Bacchi, G. Ariceta, S. Johnson, AL. Lapeyraque, and C. Nester participated to a meeting in Paris on February 26, 2014, to define the domains requiring discussion and consensus.

Four critical revisions of the article and consensus approval of the final version was given by the authors indicated above and by M. Bitzan, R. Coppo, F. Emma, D. Karpman, D. Landau, C.B. Langman, C. Licht, M. Riedl, N. van de Kar and M. Vivarelli. N. Besbas, A. Bjerre, C. Pecoraro and J. van de Walle gave approval of the revisions and final version. All authors except F. Fakhouri and V. Fremeaux-Bacchi are members of HUS International.

Declaration of interests

The following authors declare interests. G. Ariceta, F. Fakhouri, V. Fremeaux-Bacchi, S. Johnson, D. Landau, AL. Lapeyraque, C. Licht, C. Loirat and N. van de Kar have served on Advisory Boards and/or teaching courses for Alexion Pharmaceuticals. C. Licht received research grants from Alexion Pharmaceuticals. D. Karpman, C. Licht and C. Loirat were the national coordinators of the multi-center Eculizumab trials in aHUS in Sweden, Canada and France, respectively. G. Ariceta, F. Fakhouri, V. Fremeaux-Bacchi, S. Johnson, C. Licht and J. van de Valle are members of the Scientific Advisory Board of the International aHUS Registry of Alexion Pharmaceuticals. M. Bitzan and C. Loirat were scientific advisers for Thallion Pharmaceuticals. C. Licht served on Advisory Board of Achillon Pharmaceuticals.

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Loirat, C., Fakhouri, F., Ariceta, G. et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 31, 15–39 (2016). https://doi.org/10.1007/s00467-015-3076-8

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  • DOI: https://doi.org/10.1007/s00467-015-3076-8

Keywords

  • Anti-factor H antibody
  • Atypical hemolytic uremic syndrome
  • Children
  • Combined liver–kidney transplantation
  • Complement
  • Eculizumab
  • Hemolytic uremic syndrome
  • Kidney transplantation
  • Plasma exchange
  • Plasma infusion
  • Thrombotic microangiopathy