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Abstract: SA-PO576

Outcome of Atypical Hemolytic Uremic Syndrome (aHUS) Treated With C5-Inhibition, Primary vs. Secondary vs. Idiopathic: Results From the ItalKid-HUS Network

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Ardissino, Gianluigi, Center for HUS Prevention, Control and Management at Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
  • Tangredi, Marianna, Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
  • Capone, Valentina, Center for HUS Prevention, Control and Management at Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
  • Porcaro, Luigi, Medical Genetics Laboratory, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy, Milano, Italy
  • Cugno, Massimo, Medicina Interna, Dipartimento di Fisiopatologia Medico Chirurgica e dei Trapianti, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Università Degli Studi, Milano, Italy
  • Brezzi, Brigida, Presidio Ospedaliero SS Antonio e Biagio, Alessandria, Italy
  • Credendino, Olga, Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli, Napoli, Campania, Italy
  • Cirami, Lino Calouero, Ospedale Careggi, Firenze, Italy
  • Castellano, Giuseppe., Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
  • Ravera, Federica, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milano, Lombardia, Italy
  • Cresseri, Donata Carmela, Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy

Group or Team Name

  • ItalKid HUS Network
Background

Atypical Hemolytic Uremic Syndrome is a Thrombotic Microangiopathy related to complement abnormalities (genetic or acquired) in 50-60% of cases. The remaining cases may involve unknown genes, but may also be due to coexisting complement over-activating conditions acting as triggers. Based on the presence of complement abnormalities and of specific triggers, 3 groups can be identified: 1.Primary (with complement abnormality), 2.Secondary (trigger only), 3.Idiopathic (neither complement abnormality nor trigger). This approach to aHUS classification may have important drawbacks in the management of patients particularly with regards to C5 inhibition (C5i) as to treatment initiation, discontinuation and response rate.

Methods

The case series of aHUS treated or referred to our Center between 2000 and 2021 was analyzed according to the mentioned classification criteria. Response rate (RR), case-fatality rate, frequency of ESKD and relapse rate were compared between C5i and conventional treatment.

Results

Out of 240 patients, 150 (62.5%) had Primary aHUS, 55 (22.9%) Secondary aHUS and 35 (14.6%) Idiopathic aHUS. In patients treated with C5i (n:143) RR was higher within all groups (82.7% for Primary, 76.1% for Secondary and 59.1% for Idiopathic aHUS) compared to conventional treatment (38.7%, 55.6% and 53.9%, respectively). The frequency of ESKD was lower after C5i in all groups (Primary 15.7 vs 59.6%; Secondary 14.8 vs 40.4%; Idiopathic 36.0 vs 40.0%). Similarly, case-fatality rate was lower with C5i in all groups compared to conventional treatment (Primary 5.7 vs 9.5%; Secondary 8.5 vs 20.0%; Idiopathic 4.0 vs 13.0%). Among patients who discontinued C5i (n:83) the relapse rate was significantly higher in those with complement disregulation compared to patients without complement abnormalities (68.6% for Primary and 0% for both Secondary and Idiopathic aHUS).

Conclusion

Based on our results and given that aHUS patient can’t be correctly classified a priori, C5i should be promptly started in all patients meeting the criteria for aHUS. When complement dysregulation workup is available, patients can be better stratified and managed accordingly as to treatment discontinuation.