title: First-line therapy in atypical hemolytic uremic syndrome: consideration on infants with a poor prognosis.
abstract: BACKGROUND
  Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogeneous disorder. The first line treatment of aHUS is plasma therapy, but in the past few years, the recommendations have changed greatly with the advent of eculizumab, a humanized monoclonal anti C5-antibody. Although recent recommendations suggest using it as a primary treatment for aHUS, important questions have arisen about the necessity of immediate use of eculizumab in all cases. We aimed to draw attention to a specific subgroup of aHUS patients with rapid disease progression and high mortality, in whom plasma therapy may not be feasible.
  
  
  METHODS
  We present three pediatric patients of acute complement-mediated HUS with a fatal outcome. Classical and alternative complement pathway activity, levels of complement factors C3, C4, H, B and I, as well as of anti-factor H autoantibody and of ADAMTS13 activity were determined. The coding regions of CFH, CFI, CD46, THBD, CFB and C3 genes were sequenced and the copy number of CFI, CD46, CFH and related genes were analyzed.
  
  
  RESULTS
  We found severe activation and consumption of complement components in these patients, furthermore, in one patient we identified a previously not reported mutation in CFH (Ser722Stop), supporting the diagnosis of complement-mediated HUS. These patients were not responsive to the FFP therapy, and all cases had fatal outcome.
  
  
  CONCLUSIONS
  Taking the heterogeneity and the variable prognosis of atypical HUS into account, we suggest that the immediate use of eculizumab should be considered as first-line therapy in certain small children with complement dysregulation.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi st. 4, H-1125, Budapest, Hungary. nora.szarvas@gmail.com.
authors.forename: Nóra
authors.initials: N
authors.lastname: Szarvas
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi st. 4, H-1125, Budapest, Hungary. szilagi@kut.sote.hu.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Szilágyi
authors.affiliation: Department of Pediatric Nephrology, University Children's Hospital, Skopje, Macedonia. vtasic2003@gmail.com.
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.affiliation: Department of Nephrology, Pediatric Clinic, University Clinical Centre of Kosova, Prishtina, Republic of Kosovo. valbona_n@hotmail.com.
authors.forename: Valbona
authors.initials: V
authors.lastname: Nushi-Stavileci
authors.affiliation: Department of Pediatric Nephrology, University Children's Hospital, Skopje, Macedonia. aspaziculi@yahoo.com.
authors.forename: Aspazija
authors.initials: A
authors.lastname: Sofijanova
authors.affiliation: Department of Pediatric Nephrology, University Children's Hospital, Skopje, Macedonia. gucevz@gmail.com.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gucev
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary. szabo.miklos@med.semmelweis-univ.hu.
authors.forename: Miklós
authors.initials: M
authors.lastname: Szabó
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary. szabo.attila@med.semmelweis-univ.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Szabó
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary. szeifert.lilla@gmail.com.
authors.forename: Lilla
authors.initials: L
authors.lastname: Szeifert
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary. reusz.gyorgy@med.semmelweis-univ.hu.
authors.forename: György
authors.initials: G
authors.lastname: Reusz
authors.affiliation: Department of Pediatrics, Medical University Vienna, Vienna, Austria. krisztina.rusai@meduniwien.ac.at.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Rusai
authors.affiliation: Department of Pediatrics, Medical University Vienna, Vienna, Austria. klaus.arbeiter@meduniwien.ac.at.
authors.forename: Klaus
authors.initials: K
authors.lastname: Arbeiter
authors.affiliation: Department of Pediatrics, Medical University Vienna, Vienna, Austria. thomas.mueller@meduniwien.ac.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi st. 4, H-1125, Budapest, Hungary. prohoz@kut.sote.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D016913:Blood Component Transfusion / Q000379:methods*; D003165:Complement System Proteins / Q000378:metabolism; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003165:Complement System Proteins; C481642:eculizumab