دورية أكاديمية
أعرض في EDS

Outcome of atypical hemolytic uremic syndrome: role of triggers and complement abnormalities in the response to C5 inhibition.

التفاصيل البيبلوغرافية
العنوان: Outcome of atypical hemolytic uremic syndrome: role of triggers and complement abnormalities in the response to C5 inhibition.
المؤلفون: Ardissino G; Center for HUS Prevention, Control and Management at the Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy. ardissino@centroseu.org., Cresseri D; Center for HUS Prevention, Control and Management at the Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Mancuso MC; Center for HUS Prevention, Control and Management at the Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Capone V; Center for HUS Prevention, Control and Management at the Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Porcaro L; Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy., Amico V; Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy., Tangredi M; Center for HUS Prevention, Control and Management at the Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Grovetti E; Medicina Interna Dipartimento di Fisiopatologia Medico‑Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy., Griffini S; Medicina Interna Dipartimento di Fisiopatologia Medico‑Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy., Castellano G; Center for HUS Prevention, Control and Management at the Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Montini G; Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Giuliana and Bernardo Caprotti Chair of Pediatrics, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy., Consonni D; Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Cugno M; Medicina Interna Dipartimento di Fisiopatologia Medico‑Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
مؤلفون مشاركون: HUS-ItalKid Network.
المصدر: Journal of nephrology [J Nephrol] 2024 May; Vol. 37 (4), pp. 1017-1026. Date of Electronic Publication: 2024 Jan 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: Italy NLM ID: 9012268 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1724-6059 (Electronic) Linking ISSN: 11218428 NLM ISO Abbreviation: J Nephrol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2014- : Heidelberg : Springer
Original Publication: Rome : Acta Medica,
مواضيع طبية MeSH: Atypical Hemolytic Uremic Syndrome*/drug therapy , Antibodies, Monoclonal, Humanized*/therapeutic use , Complement C5*/antagonists & inhibitors, Humans ; Male ; Female ; Adult ; Treatment Outcome ; Kidney Failure, Chronic/etiology ; Complement Inactivating Agents/therapeutic use ; Retrospective Studies ; Adolescent ; Young Adult ; Recurrence ; Middle Aged ; Complement Activation/drug effects ; Child ; Risk Factors ; Time Factors
مستخلص: Background: Atypical-hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy often due to uncontrolled complement activation, characterized by high risk of end-stage kidney disease (ESKD). Eculizumab has improved the outcome, however, its efficacy varies among patients and its discontinuation is debated.
Methods: To identify characteristics associated with treatment response, we analyzed 244 aHUS patients referred to our center. Patients were classified according to the presence/absence of complement abnormalities and/or triggers at onset in 4 categories: (1) primary (complement abnormality without trigger), (2) secondary (trigger without complement abnormality), (3) combined (trigger and complement abnormality), (4) idiopathic (no trigger, no complement abnormality). Response to treatment was evaluated by comparing the response to eculizumab with that of conventional therapy. Short- and long-term outcomes were evaluated with the relapse rate after discontinuation of C5-inhibition.
Results: Patients had a better outcome with eculizumab compared to conventional treatment, with a response rate of 81.9% vs 56.9%, p < 0.001 and a long-term cumulative incidence of ESKD of 5.8% vs 22.5% (hazard ratio 0.25, 95% confidence interval: 0.10-0.80). The excellent global response was driven by the primary and combined groups (89.8% vs 54.0% and 89.3% vs 54.2%, respectively). The relapse rate following discontinuation of the C5-inhibitor was as high as 66.7% in the primary group, 18.7% in the combined, and 0% in the secondary and idiopathic groups.
Conclusions: Our data show a better outcome in aHUS patients treated with C5-inhibition, particularly in the primary and combined forms, which have a high risk of relapse after discontinuation that is not observed in the secondary and idiopathic forms.
(© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)
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فهرسة مساهمة: Investigator: A Barbara; A Alessandro; A Carlo; A Karen; A Alice; B Bruno; B Maria; B Alessandra; B Brigida; B Maurizio; B Alessandro; C Valeria; C Leonardo; C Alessandra; C Aldo; C Donatella; C Nicola; C Alessandro; C Francesco; C Doriana; C Calogero; C Giacomo; C Ciro; C Luigia; C Raffaella; C Olga; D' Marco; D Delia; Biase; Philippis; D Nunzia; D Vecchio; F Luca; F Roberta; F Angelo; F Domenico; F Maria; F Riccardo; F Lucrezia; G Andrea; G Giovanni; G Fabio; G Mario; G Gina; I Francesco; I Alessandro; Scola; L Selena; M Annunziata; M Carmelita; M Rita; M Silvio; M Jacopo; M Sarah; M Verna; M Laura; M Marco; M Florjan; M Alessandra; M Concetta; M Sabrina; M Cristina; M Tommaso; M Enrico; M Nicola; N Valentina; M Lorenza; N Alessandro; N Maria; O Francesco; P Fabio; P Giuseppe; P Antonello; P Andrea; P Werner; P Jacopo; P Giorgio; P Giulia; P Lucia; P Gianmarco; P Vera; P Ilaria; P Leonardo; R Teresa; R Andrea; R Angelo; R Barbara; R Angelo; R Evangeline; R Roberto; R Rodolfo; S Laura; S Paola; S Chiara; S Fabian; S Giuseppe; S Chiara; S Tiziana; T Elisabetta; T Monica; T Sara; T Aristide; T Lorella; T Chiara; T Francesco; T Laura; T Silvia; T Martina; V Pellu; V Paolo; V Simona; V Marta; V Enrico; V Giuseppe; V Luca; Z Marco; V Luca; Z Marco; M Domenico
Keywords: C5inhibition; Complement abnormalities; Complement dysregulation; aHUS
المشرفين على المادة: A3ULP0F556 (eculizumab)
0 (Antibodies, Monoclonal, Humanized)
0 (Complement C5)
0 (Complement Inactivating Agents)
تواريخ الأحداث: Date Created: 20240127 Date Completed: 20240711 Latest Revision: 20240715
رمز التحديث: 20240715
DOI: 10.1007/s40620-023-01873-9
PMID: 38280096
قاعدة البيانات: MEDLINE
الوصف
تدمد:1724-6059
DOI:10.1007/s40620-023-01873-9