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Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study

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Abstract

Background

Hemolytic uremic syndrome related to Shiga-toxin-secreting Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney injury in young children. No specific treatment has been validated for this severe disease. Recently, experimental studies highlight the potential role of complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody against terminal complement complex, has been used in severe STEC-HUS patients, mostly during the 2011 German outbreak, with conflicting results.

Methods

On behalf of the French Society of Pediatric Nephrology, we retrospectively studied 33 children from 15 centers treated with EC for severe STEC-HUS. Indication for EC was neurologic involvement in 20 patients, cardiac and neurologic involvement in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical status at last follow-up, patients were divided into two groups: favorable (n = 15) and unfavorable outcomes (n = 18).

Results

Among patients with favorable outcome, 11/14 patients (79%) displayed persistent blockade of complement activity before each EC reinjection. Conversely, in patients with unfavorable outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients presenting neurological symptoms, 19 had favorable neurological outcome including 17 with prompt recovery following first EC injection. Only two adverse effects potentially related to EC treatment were reported.

Conclusions

Taken together, these results may support EC use in severe STEC-HUS patients, especially those presenting severe neurological symptoms. The study, however, is limited by absence of a control group and use of multiple therapeutic interventions in treatment groups. Thus, prospective, controlled trials should be undertaken.

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Authors and Affiliations

  1. Service de Néphrologie Pédiatrique, Hôpital des enfants, CHU Purpan, Toulouse, France

    Lucas Percheron, Stéphanie Tellier & Arnaud Garnier

  2. Service de Neuroradiologie Diagnostique et Thérapeutique, CHU Purpan, Toulouse, France

    Raluca Gramada

  3. Service de Néphrologie Pédiatrique, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France

    Remi Salomon

  4. Service de Néphrologie Pédiatrique, Hôpital Pellegrin-Enfants, CHU Bordeaux, Bordeaux, France

    Jérôme Harambat & Brigitte Llanas

  5. Service de Néphrologie Pédiatrique, Hôpital Robert Debré-Paris, Assistance Publique-Hôpitaux de Paris, Paris, France

    Marc Fila

  6. Service de Néphrologie Pédiatrique, Hôpital Mère-Enfants, CHU Nantes, Nantes, France

    Emma Allain-Launay

  7. Service de Néphrologie Pédiatrique, CHU de Sainte-Justine à Montréal Canada, Montréal, Canada

    Anne-Laure Lapeyraque

  8. Service de Néphrologie Pédiatrique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France

    Valerie Leroy

  9. Service de Néphrologie Pédiatrique, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France

    Anne-Laure Adra

  10. Service de Néphrologie Pédiatrique, Hôpital Archet 2, CHU Nice, Nice, France

    Etienne Bérard

  11. Service de pédiatrie, Hôpital Couple-Enfants, CHU Grenoble, Grenoble, France

    Guylhène Bourdat-Michel

  12. Service de Néphrologie Pédiatrique, CHU de Lausanne Suisse, Lausanne, Switzerland

    Hassid Chehade

  13. Service de Pédiatrie Médicale, Hôpital côte de nacre, CHU Caen, Caen, France

    Philippe Eckart

  14. Service de Néphrologie, Hôpital Clocheville, CHU Tours, Tours, France

    Elodie Merieau

  15. Service de Pédiatrie, Hôpital Américain, CHU Reims, Reims, France

    Christine Piètrement

  16. Service de Néphrologie Pédiatrique, Hôpital femme mère enfant, Hospices Civils de Lyon, Lyon, France

    Anne-Laure Sellier-Leclerc

  17. Laboratoire d’immunologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France

    Véronique Frémeaux-Bacchi

  18. Biostatistiques, Informatique Médicale, UMR 1027 Inserm, Université Paul Sabatier, Toulouse, France

    Chloe Dimeglio

Authors
  1. Lucas Percheron
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  2. Raluca Gramada
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  3. Stéphanie Tellier
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  4. Remi Salomon
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  5. Jérôme Harambat
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  6. Brigitte Llanas
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  7. Marc Fila
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  8. Emma Allain-Launay
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  9. Anne-Laure Lapeyraque
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  10. Valerie Leroy
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  11. Anne-Laure Adra
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  12. Etienne Bérard
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  13. Guylhène Bourdat-Michel
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  14. Hassid Chehade
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  15. Philippe Eckart
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  16. Elodie Merieau
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  17. Christine Piètrement
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  18. Anne-Laure Sellier-Leclerc
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  19. Véronique Frémeaux-Bacchi
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  20. Chloe Dimeglio
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  21. Arnaud Garnier
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Corresponding authors

Correspondence to Lucas Percheron or Arnaud Garnier.

Ethics declarations

All parents gave informed consent for their children. The National Code on Clinical Trials has declared that ethics approval is not necessary for retrospective studies.

Conflict of interest

The authors declare that they have no conflict of interest.

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Percheron, L., Gramada, R., Tellier, S. et al. Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study. Pediatr Nephrol 33, 1385–1394 (2018). https://doi.org/10.1007/s00467-018-3903-9

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  • DOI: https://doi.org/10.1007/s00467-018-3903-9

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