BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9). CASE-DIAGNOSIS/TREATMENT: We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses. CONCLUSIONS: Not every patient with aHUS and uncontrolled complement activation shows optimal therapeutic response to eculizumab with the recommended or even increased dosing regimen. Reliable outcome measures to determine the efficacy of treatment have to be defined.
BACKGROUND:Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9). CASE-DIAGNOSIS/TREATMENT: We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses. CONCLUSIONS: Not every patient with aHUS and uncontrolled complement activation shows optimal therapeutic response to eculizumab with the recommended or even increased dosing regimen. Reliable outcome measures to determine the efficacy of treatment have to be defined.
Authors: C S Rinder; H M Rinder; B R Smith; J C Fitch; M J Smith; J B Tracey; L A Matis; S P Squinto; S A Rollins Journal: J Clin Invest Date: 1995-09 Impact factor: 14.808
Authors: Frank Bienaime; Marie-Agnes Dragon-Durey; Catherine H Regnier; Sara C Nilsson; Wing H Kwan; Jacques Blouin; Mathieu Jablonski; Nicolas Renault; Marie-Anne Rameix-Welti; Chantal Loirat; Catherine Sautés-Fridman; Bruno O Villoutreix; Anna M Blom; Veronique Fremeaux-Bacchi Journal: Kidney Int Date: 2009-12-16 Impact factor: 10.612
Authors: Iain Moore; Lisa Strain; Isabel Pappworth; David Kavanagh; Paul N Barlow; Andrew P Herbert; Christoph Q Schmidt; Scott J Staniforth; Lucy V Holmes; Roy Ward; Lynn Morgan; Timothy H J Goodship; Kevin J Marchbank Journal: Blood Date: 2009-10-27 Impact factor: 22.113
Authors: C M Legendre; C Licht; P Muus; L A Greenbaum; S Babu; C Bedrosian; C Bingham; D J Cohen; Y Delmas; K Douglas; F Eitner; T Feldkamp; D Fouque; R R Furman; O Gaber; M Herthelius; M Hourmant; D Karpman; Y Lebranchu; C Mariat; J Menne; B Moulin; J Nürnberger; M Ogawa; G Remuzzi; T Richard; R Sberro-Soussan; B Severino; N S Sheerin; A Trivelli; L B Zimmerhackl; T Goodship; C Loirat Journal: N Engl J Med Date: 2013-06-06 Impact factor: 91.245
Authors: Markus J Harder; Nadine Kuhn; Hubert Schrezenmeier; Britta Höchsmann; Inge von Zabern; Christof Weinstock; Thomas Simmet; Daniel Ricklin; John D Lambris; Arne Skerra; Markus Anliker; Christoph Q Schmidt Journal: Blood Date: 2016-12-27 Impact factor: 22.113
Authors: C Wehling; O Amon; M Bommer; B Hoppe; K Kentouche; G Schalk; R Weimer; M Wiesener; B Hohenstein; B Tönshoff; R Büscher; H Fehrenbach; Ö-N Gök; M Kirschfink Journal: Clin Exp Immunol Date: 2016-11-25 Impact factor: 4.330
Authors: Stefan Michelfelder; Friedericke Fischer; Astrid Wäldin; Kim V Hörle; Martin Pohl; Juliana Parsons; Ralf Reski; Eva L Decker; Peter F Zipfel; Christine Skerka; Karsten Häffner Journal: J Am Soc Nephrol Date: 2018-01-15 Impact factor: 10.121
Authors: Camino García Monteavaro; Carmen Peralta Roselló; Borja Quiroga; José María Baltar Martín; Lorena Castillo Eraso; Fernando de Álvaro Moreno; Alberto Martínez Vea; María Teresa Visus-Fernández de Manzanos Journal: Case Rep Nephrol Date: 2016-11-29
Authors: Manuel Macia; Fernando de Alvaro Moreno; Tina Dutt; Ingela Fehrman; Karine Hadaya; Christoph Gasteyger; Nils Heyne Journal: Clin Kidney J Date: 2016-12-22
Authors: Sejin Kim; Eujin Park; Sang Il Min; Nam Joon Yi; Jongwon Ha; Il Soo Ha; Hae Il Cheong; Hee Gyung Kang Journal: J Korean Med Sci Date: 2018-01-01 Impact factor: 2.153
Authors: Jin Y Chen; Neeti S Galwankar; Heather N Emch; Smrithi S Menon; Claudio Cortes; Joshua M Thurman; Samuel A Merrill; Robert A Brodsky; Viviana P Ferreira Journal: Front Immunol Date: 2020-07-22 Impact factor: 7.561