title: An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document.
abstract: Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Different causes can induce the TMA process that characterizes HUS. In this document we consider atypical HUS (aHUS) a sub-type of HUS in which the TMA phenomena are the consequence of the endotelial damage in the microvasculature of the kidneys and other organs due to a disregulation of the activity of the complement system. In recent years, a variety of aHUs-related mutations have been identified in genes of the the complement system, which can explain approximately 60% of the aHUS cases, and a number of mutations and polymorphisms have been functionally characterized. These findings have stablished that aHUS is a consequence of the insufficient regulation of the activiation of the complement on cell surfaces, leading to endotelial damage mediated by C5 and the complement terminal pathway. Eculizumab is a monoclonal antibody that inhibits the activation of C5 and blocks the generation of the pro-inflammatory molecule C5a and the formation of the cell membrane attack complex. In prospective studies in patients with aHUS, the use of Eculizumab has shown a fast and sustained interruption of the TMA process and it has been associated with significative long-term improvements in renal function, the interruption of plasma therapy and important reductions in the need of dialysis. According to the existing literature and the accumulated clinical experience, the Spanish aHUS Group published a consensus document with recommendations for the treatment of aHUs (Nefrologia 2013;33[1]:27-45). In the current online version of this document, we update the aetiological classification of TMAs, the pathophysiology of aHUS, its differential diagnosis and its therapeutic management.
authors.affiliation: Servicio de Nefrología, Hospital Clínic, Barcelona, España. Electronic address: JMCAMPIS@clinic.ub.es.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.affiliation: Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander, España.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.affiliation: Servicio de Nefrología Pediátrica, Hospital Universitari Materno-Infantil Vall d'Hebrón, Universidad Autónoma de Barcelona, Barcelona, España.
authors.forename: Gema
authors.initials: G
authors.lastname: Ariceta
authors.affiliation: Servicio de Nefrología, Hospital Clínic, Barcelona, España.
authors.forename: Miguel
authors.initials: M
authors.lastname: Blasco
authors.affiliation: Servicio de Nefrología Pediátrica, Hospital La Paz, Madrid, España.
authors.forename: Laura
authors.initials: L
authors.lastname: Espinosa
authors.affiliation: Servicio de Nefrología, Hospital Universitario Reina Sofía, Córdoba, España.
authors.forename: Mario
authors.initials: M
authors.lastname: Espinosa
authors.affiliation: Servicio de Nefrología, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, España.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.affiliation: Servicio de Nefrología, Hospital Virgen de la Candelaria, Santa Cruz de Tenerife, España.
authors.forename: Manuel
authors.initials: M
authors.lastname: Macía
authors.affiliation: Servicio de Nefrología Pediátrica, Hospital La Fe, Valencia, España.
authors.forename: Santiago
authors.initials: S
authors.lastname: Mendizábal
authors.affiliation: Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España.
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.affiliation: Servicio de Nefrología Pediátrica, Hospital La Fe, Valencia, España.
authors.forename: Elena
authors.initials: E
authors.lastname: Román
authors.affiliation: Enfermedades Renales Hereditarias, Fundació Puigvert, Barcelona, España.
authors.forename: Roser
authors.initials: R
authors.lastname: Torra
authors.affiliation: Servicio de Nefrología, Complejo Hospitalario A Coruña, A Coruña, España.
authors.forename: Francisco
authors.initials: F
authors.lastname: Valdés
authors.affiliation: Servicio de Nefrología Pediátrica, Hospital Universitari Materno-Infantil Vall d'Hebrón, Universidad Autónoma de Barcelona, Barcelona, España.
authors.forename: Ramón
authors.initials: R
authors.lastname: Vilalta
authors.affiliation: Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biológicas (CSIC), Madrid, España.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez de Córdoba
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D003167:Complement Activation; D003182:Complement C5 / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics; D019468:Disease Management; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D016030:Kidney Transplantation; D010951:Plasma Exchange; D011379:Prognosis; D012008:Recurrence; D012697:Serine Endopeptidases / Q000627:therapeutic use; D057049:Thrombotic Microangiopathies / Q000145:classification / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; C041833:complement C5a-inhibitors; D003165:Complement System Proteins; C481642:eculizumab; D012697:Serine Endopeptidases
keywords: Atypical haemolytic uraemic syndrome; Complement; Complemento; Eculizumab; Microangiopatía trombótica; Síndrome hemolítico urémico atípico; Thrombotic microangiopathy