Lucas Percheron1, Raluca Gramada2, Stéphanie Tellier3, Remi Salomon4, Jérôme Harambat5, Brigitte Llanas5, Marc Fila6, Emma Allain-Launay7, Anne-Laure Lapeyraque8, Valerie Leroy9, Anne-Laure Adra10, Etienne Bérard11, Guylhène Bourdat-Michel12, Hassid Chehade13, Philippe Eckart14, Elodie Merieau15, Christine Piètrement16, Anne-Laure Sellier-Leclerc17, Véronique Frémeaux-Bacchi18, Chloe Dimeglio19, Arnaud Garnier20. 1. Service de Néphrologie Pédiatrique, Hôpital des enfants, CHU Purpan, Toulouse, France. percheron.l@chu-toulouse.fr. 2. Service de Neuroradiologie Diagnostique et Thérapeutique, CHU Purpan, Toulouse, France. 3. Service de Néphrologie Pédiatrique, Hôpital des enfants, CHU Purpan, Toulouse, France. 4. Service de Néphrologie Pédiatrique, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France. 5. Service de Néphrologie Pédiatrique, Hôpital Pellegrin-Enfants, CHU Bordeaux, Bordeaux, France. 6. Service de Néphrologie Pédiatrique, Hôpital Robert Debré-Paris, Assistance Publique-Hôpitaux de Paris, Paris, France. 7. Service de Néphrologie Pédiatrique, Hôpital Mère-Enfants, CHU Nantes, Nantes, France. 8. Service de Néphrologie Pédiatrique, CHU de Sainte-Justine à Montréal Canada, Montréal, Canada. 9. Service de Néphrologie Pédiatrique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France. 10. Service de Néphrologie Pédiatrique, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France. 11. Service de Néphrologie Pédiatrique, Hôpital Archet 2, CHU Nice, Nice, France. 12. Service de pédiatrie, Hôpital Couple-Enfants, CHU Grenoble, Grenoble, France. 13. Service de Néphrologie Pédiatrique, CHU de Lausanne Suisse, Lausanne, Switzerland. 14. Service de Pédiatrie Médicale, Hôpital côte de nacre, CHU Caen, Caen, France. 15. Service de Néphrologie, Hôpital Clocheville, CHU Tours, Tours, France. 16. Service de Pédiatrie, Hôpital Américain, CHU Reims, Reims, France. 17. Service de Néphrologie Pédiatrique, Hôpital femme mère enfant, Hospices Civils de Lyon, Lyon, France. 18. Laboratoire d'immunologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. 19. Biostatistiques, Informatique Médicale, UMR 1027 Inserm, Université Paul Sabatier, Toulouse, France. 20. Service de Néphrologie Pédiatrique, Hôpital des enfants, CHU Purpan, Toulouse, France. garnier.a@chu-toulouse.fr.
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.
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-HUSpatients, 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-HUSpatients, 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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