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

期刊论文
发表日期：

2024年1月27日

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Gianluigi Ardissino,
Donata Cresseri,
Maria Cristina Mancuso,
Valentina Capone,
Luigi Porcaro,
Valeria Amico,
Marianna Tangredi,
Elena Grovetti,
Samantha Griffini,
Giuseppe Castellano,
Giovanni Montini,
Dario Consonni,
Massimo Cugno,
Acaia Barbara,
Aiuti Alessandro,
Alfieri Carlo,
Amar Karen,
Atzeni Alice,
Basolo Bruno,
Bernardo Maria,
Biffi Alessandra,
Brezzi Brigida,
Brigante Maurizio,
Bucalossi Alessandro,
Calbi Valeria,
Caroti Leonardo,
Carotti Alessandra,
Casani Aldo,
Casartelli Donatella,
Cassata Nicola,
Castiglioni Alessandro,
Catalano Francesco,
Chiarinotti Doriana,
Cirami Calogero,
Colussi Giacomo,
Corrado Ciro,
Costantini Luigia,
Cravero Raffaella,
Credendino Olga,
D.’Amico Marco,
Davoli Delia,
De Biase,
De Philippis,
Decembrino Nunzia,
Del Vecchio,
Facchini Luca,
Fenoglio Roberta,
Ferrantelli Angelo,
Ferrara Domenico,
Fischer Maria,
Floreani Riccardo,
Furian Lucrezia,
Galassi Andrea,
Gambaro Giovanni,
Giglio Fabio,
Giordano Mario,
Gregorini Gina,
Iannuzzella Francesco,
Inzoli Alessandro,
La Scola,
Longhi Selena,
Marangelli Annunziata,
Marcantoni Carmelita,
Marinelli Rita,
Maringhini Silvio,
Mariotti Jacopo,
Marktel Sarah,
Marta Verna,
Martelli Laura,
Martini Marco,
Mehemeti Florjan,
Messuerotti Alessandra,
Micalizzi Concetta,
Milan Sabrina,
Milocco Cristina,
Mina Tommaso,
Minetti Enrico,
Mongera Nicola,
Nastasi Valentina,
Morabito Lorenza,
Naticchia Alessandro,
Neunhauser Maria,
Onida Francesco,
Paglialonga Fabio,
Palladino Giuseppe,
Pani Antonello,
Pasini Andrea,
Passler Werner,
Peccatori Jacopo,
Piaggio Giorgio,
Pintarelli Giulia,
Pisano Lucia,
Podda Gianmarco,
Polaschi Vera,
Possenti Ilaria,
Potenza Leonardo,
Rampino Teresa,
Ranghino Andrea,
Ravelli Angelo,
Ravera Barbara,
Rigotti Angelo,
Rodrigues Evangeline,
Rona Roberto,
Russo Rodolfo,
Sainati Laura,
Salis Paola,
Salviani Chiara,
Schumacher Fabian,
Seminara Giuseppe,
Somma Chiara,
Stellato Tiziana,
Terruzzi Elisabetta,
Terenziani Monica,
Testa Sara,
Torre Aristide,
Torretta Lorella,
Trenti Chiara,
Trepiccioni Francesco,
Trespidi Laura,
Trisolini Silvia,
Tubaro Martina,
Valentina Pellu,
Vercelloni Paolo,
Verdesca Simona,
Verna Marta,
Verrina Enrico,
Visconti Giuseppe,
Visconti Luca,
Zecca Marco,
Visconti Luca,
Zecca Marco,
Minasi Domenico

摘要

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.

Graphical abstract