title: 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.
authors: Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Department of Pediatric Nephrology, Université Paris Diderot Sorbonne Paris Cité, Paris, France. chantal.loirat@rdb.aphp.fr.
authors: Chantal
authors: C
authors: Loirat
authors: Centre Hospitalier Universitaire de Nantes, Department of Nephrology and Immunology, ITUN and INSERM UMR S-1064, Nantes, France.
authors: Fadi
authors: F
authors: Fakhouri
authors: Pediatric Nephrology, Vall d'Hebron Hospital, Autonoma University of Barcelona, Barcelona, Spain.
authors: Gema
authors: G
authors: Ariceta
authors: Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors: Nesrin
authors: N
authors: Besbas
authors: Division of Nephrology, Montreal Children's Hospital and Mc Gill University, Montreal, Canada.
authors: Martin
authors: M
authors: Bitzan
authors: Department of Pediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors: Anna
authors: A
authors: Bjerre
authors: City of the Health and the Science of Turin Health Agency, Regina Margherita Children's Hospital, Turin, Italy.
authors: Rosanna
authors: R
authors: Coppo
authors: Bambino Gesù Children's Hospital, Rome, Italy.
authors: Francesco
authors: F
authors: Emma
authors: Department of Paediatric Nephrology, Great North Children's Hospital, Newcastle Upon Tyne, UK.
authors: Sally
authors: S
authors: Johnson
authors: Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden.
authors: Diana
authors: D
authors: Karpman
authors: Soroka University Medical Center, Beer Sheva, Israel.
authors: Daniel
authors: D
authors: Landau
authors: The Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: Craig B
authors: CB
authors: Langman
authors: Service de Néphrologie, Département de Pédiatrie, CHU Sainte-Justine, Université de Montréal, Montréal, Canada.
authors: Anne-Laure
authors: AL
authors: Lapeyraque
authors: The Hospital for Sick Children, Toronto, Canada.
authors: Christoph
authors: C
authors: Licht
authors: Departments of Internal Medicine and the Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
authors: Carla
authors: C
authors: Nester
authors: Santobono Children's Hospital, Naples, Italy.
authors: Carmine
authors: C
authors: Pecoraro
authors: Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria.
authors: Magdalena
authors: M
authors: Riedl
authors: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Nicole C A J
authors: NC
authors: van de Kar
authors: University Hospital Ghent, Ghent, Belgium.
authors: Johan
authors: J
authors: Van de Walle
authors: Bambino Gesù Children's Hospital, Rome, Italy.
authors: Marina
authors: M
authors: Vivarelli
authors: Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Laboratory of Immunology, INSERM UMRS 1138, Paris, France.
authors: Véronique
authors: V
authors: Frémeaux-Bacchi
mesh_terms: D000293:Adolescent; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003167:Complement Activation / Q000187:drug effects; D003299:Cooperative Behavior; D016903:Drug Monitoring; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007391:International Cooperation; D016030:Kidney Transplantation; D016031:Liver Transplantation; D015166:Monitoring, Immunologic; D009398:Nephrology / Q000592:standards*; D018579:Patient Selection; D010951:Plasma Exchange; D011237:Predictive Value of Tests; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C481642:eculizumab
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