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  • Review Article
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Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies

Nature Reviews Nephrology volume 8, pages 643–657 (2012)Cite this article

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Abstract

In the past decade, a large body of evidence has accumulated in support of the critical role of dysregulation of the alternative complement pathway in atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathies. These findings have paved the way for innovative therapeutic strategies based on complement blockade, and eculizumab, a monoclonal antibody targeting the human complement component 5, is now widely used to treat aHUS. In this article, we review 28 case reports and preliminary data from 37 patients enrolled in prospective trials of eculizumab treatment for episodes of aHUS involving either native or transplanted kidneys. Eculizumab may be considered as an optimal first-line therapy when the diagnosis of aHUS is unequivocal and this treatment has the potential to rescue renal function when administered early after onset of the disease. However, a number of important issues require further study, including the appropriate duration of treatment according to an individual's genetic background and medical history, the optimal strategy to prevent post-transplantation recurrence of aHUS and a cost–efficacy analysis. Data regarding the efficacy of eculizumab in the control of C3 glomerulopathies are more limited and less clear, but several observations suggest that eculizumab may act on the most inflammatory forms of this disorder.

Key Points

  • Eculizumab has shown greater efficacy than plasma therapy in the prevention and treatment of episodes of atypical haemolytic uraemic syndrome (aHUS)

  • Eculizumab may be considered as a first-line therapy in children with a first episode of aHUS as it avoids the complications associated with apheresis and central venous catheters

  • In adults, eculizumab can be used as a first-line therapy when aHUS diagnosis is undisputable, although plasma therapy should be used as a first-line therapy if uncertainty in diagnosis warrants further investigation

  • Evidence of plasma resistance or dependence should lead to a prompt switch to eculizumab; the sooner eculizumab is initiated, the better the recovery of renal function

  • Renal transplant candidates with a genetically determined risk of post-transplantation aHUS recurrence should be given a prophylactic protocol based on eculizumab if at high risk, and plasma exchange or eculizumab if at moderate risk

  • Eculizumab may be effective in curbing part of the inflammatory process involved in a subset of C3 glomerulopathies

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Figure 1: Eculizumab: molecular structure and mode of action.
Figure 2: Recovery of renal function is better with a shorter interval between onset of aHUS and initiation of eculizumab.
Figure 3: Diagnostic algorithm and therapeutic options for aHUS.
Figure 4: Risk assessment for patients with aHUS who are candidates for renal transplantation.

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Acknowledgements

The authors would like to thank all members of the French Study Group for aHUS/MPGN who participated in fruitful and constructive discussions regarding these recommendations: M. Buchler (Tours, France), S. Burtey (Marseille, France), D. Chauveau (Toulouse, France), Y. Delmas (Bordeaux, France), G. Deschênes (Paris, France), A. Garnier (Toulouse, France), M. Y. Hourmant (Nantes, France), A. Karras (Paris, France), B. Knebelmann (Paris, France), Y. Lebranchu (Tours, France), B. Legallicier (Rouen, France), C. Legendre (Paris, France), M. Le Quintrec (Suresnes, France), B. Moulin (Strasbourg, France), P. Niaudet (Paris, France), C. Pouteil-Noble (Lyon, France), F. Provost (Lille, France), B. Ranchin (Lyon, France) and E. Rondeau (Paris, France). The authors would also like to thank the following for providing updated data on late outcomes of their patients: S. Al-Akash (Driscoll Children's Hospital, Texas, USA), G. Ardissimo (Osp. Maggiore Policlinico, Milan, Italy), G. Ariceta (Hospital Universitario Cruces, Barakaldo-Bilbao, Spain), J. M. Campistol (Hospital Clinic, ICNU, University of Barcelona, Spain), S. Cataland (Ohio State University, Columbus, USA), J. C. Davin (Emma Children's Hospital, Amsterdam, The Netherlands), E. M. Dorresteijn (Sophia Children's Hospital, Rotterdam, The Netherlands), R. Gruppo (Cincinnati Children's Hospital, USA), K. Halka (The Texas A&M Health Science Center College of Medicine, Temple USA), N. Heyne (University Hospital Tuebingen, Germany), A. L. Lapeyrague (CHU Ste-Justine, Montréal, Canada), M. Lozano (Hospital Clinic, IDIBAPS, University of Barcelona, Spain), C. Nester (University of Iowa Hospitals and Clinics, USA), J. Nürnberger (University Duisburg-Essen, Germany), R. Ramos (Hospital Vall d'Hebron, Barcelona, Spain), C. Reid and J. J. Kim (Evelina Children's Hospital, London, UK), M. Riedl (Medical University Innsbruck, Austria), F. Schaefer (Medical University of Heidelberg, Germany), G. D. Simonetti (Children's Hospital University of Bern, Switzerland), and M. Weitz (University Children's Hospital Tuebingen, Germany).

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Authors and Affiliations

  1. Service de Transplantation Rénale Adulte, Hôpital Necker, 161 rue de Sèvres, Paris, 75015, France

    Julien Zuber

  2. Département de Nephrologie, CHU de Nantes, 1 place Alexis-Ricordeau, Nantes, 44000, France

    Fadi Fakhouri

  3. INSERM UMRS 872, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, Paris, 75006, France

    Lubka T. Roumenina

  4. Service de Néphrologie, Hôpital Robert Debré, 48 Boulevard Sérurierm, Paris, 75019, France

    Chantal Loirat

  5. Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, 20–40 rue Leblanc, Paris, 75908, France

    Véronique Frémeaux-Bacchi

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  1. Julien Zuber
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  2. Fadi Fakhouri
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  3. Lubka T. Roumenina
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on behalf of the French Study Group for aHUS/C3G

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The authors contributed equally to all aspects of the manuscript.

Corresponding author

Correspondence to Véronique Frémeaux-Bacchi.

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Competing interests

J. Zuber, F. Fakhouri, C. Loirat and V. Frémeaux-Bacchi have received fees from Alexion Pharmaceuticals for invited lectures and participation on advisory boards. L. T. Roumenina declares no competing interests.

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Zuber, J., Fakhouri, F., Roumenina, L. et al. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8, 643–657 (2012). https://doi.org/10.1038/nrneph.2012.214

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