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Observational Study
. 2025 Dec;38(9):2841-2850.
doi: 10.1007/s40620-025-02366-7. Epub 2025 Oct 17.

Clinical and genetic characteristics of patients diagnosed with atypical hemolytic uremic syndrome (aHUS): epidemiological data from the Belgian cohort of the Global aHUS Registry

Annick Massart  1 , Laurent Weekers  2 , Kathleen J Claes  3   4 , Tess Van Meerhaeghe  5 , Evelien Snauwaert  6 , Djalila Mekahli  7   8 , Eric Goffin  9 , Laure Collard  10 , Nathalie Godefroid  11 , Brigitte Adams  7   12 , Stefan Van Cauwelaert  13 , Koenraad Van Hoeck  14 , Sebastien Block  15 , Imad Al-Dakkak  16 , Karin Dahan  9   17 , Patrick Stordeur #  18 , Johan Vande Walle #  6
Affiliations
Observational Study

Clinical and genetic characteristics of patients diagnosed with atypical hemolytic uremic syndrome (aHUS): epidemiological data from the Belgian cohort of the Global aHUS Registry

Annick Massart et al. J Nephrol. 2025 Dec.

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) usually results from an overactivation of the alternative complement pathway. As large clinical trials are scarce, patient registries can partially fill the knowledge gap on patient characteristics, management, and outcomes. We here describe the baseline clinical and genetic characteristics as well as the management of all Belgian patients enrolled in the Global aHUS Registry at data cut-off.

Methods: This observational study prospectively and retrospectively collected data (data cut-off: December 26, 2022) from patients of all ages with a clinical diagnosis of aHUS, irrespective of treatment.

Results: A total of 121 Belgian patients were registered in the Global aHUS Registry, resulting in a prevalence of 10.4 aHUS patients per million inhabitants, with a higher proportion of females affected (57.9% vs 42.1% of males). Among the 109 patients tested for at least one variant and/or anti-complement factor H (CFH) antibodies, 36 were positive for a pathogenic complement gene variant associated with aHUS (n = 29) and/or seropositive for anti-CFH antibodies (n = 14). The most common variants affected CFH, C3 and CD46. The higher proportion of complement gene variants in treated women versus men was not related to a specific gene.

Conclusions: This study strengthens the real-world evidence on aHUS and adds to previously published Global aHUS Registry data. In addition, it provides insights into the differential epidemiology of the disease in Belgium and demonstrates the increased susceptibility of women to aHUS across the whole spectrum of recognized complement gene variants.

Keywords: Epidemiology; Gender; Prevalence; aHUS Registry.

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Conflict of interest statement

Declarations. Conflict of interest: Annick Massart received consulting fees from Alexion and Hansa, and support for attending meetings from Hansa (through her institution). She participated on a Data Safety Monitoring Board or Advisory Board for Novartis (through her institution). Laurent Weekers received support for attending meetings from AstraZeneca and participated in Advisory Boards for Alexion, Hanza, and Amicus. Kathleen J Claes received consulting fees from Alexion, Amgen, Novartis, and Sobi; honoraria for lectures from AstraZeneca; support for attending meetings and/or travel from Bayer. She participated on a Data Safety Monitoring Board or Advisory Board for Novartis and has a leadership or fiduciary role in other board, society, committee or advocacy groups for the Belgian Society of Nephrology. She is a member of the European Reference Network for Rare Kidney Diseases (ERKNet). Evelien Snauwaert is the beneficiary of a budget from the Fonds voor Innovatie en Klinisch Onderzoek (FIKO) type III from the Ghent University Hospital, received support from Alexion for meetings/travel and participated to a Data Safety Monitoring Committee/Advisory Board from Alexion. She is a member of the ERKNet. Djalila Mekahli received grants from Otsuka and Galapagos. She is supported by the Research Foundation Flanders (FWO; G0C8920N) and received a clinical senior research grant (1804123N). Laure Collard received consulting fees for an advisory board from Alexion (through her institution), and from Anlynam and Chiesi (through her company); consulting fees for symposium moderation from Anlynam and Chiesi (through her company); payment for lectures from Anlynam and Sandoz (through her company); payment for expert testimony from Twinpharma (through her company); financial support for attending meetings from Chiesi. Nathalie Godefroid participated to a Data Safety Monitoring Board or Advisory Board for Alexion. Koenraad Van Hoeck received honoraria for lectures from Thomas More Highschool (through his institution). Sebastien Block is an employee of Alexion Pharmaceuticals. Imad Al-Dakkak was an employee of Alexion Pharmaceuticals at the time of the study conduct, and he owns AstraZeneca stocks. Karin Dahan received grants from Alnylam (through her institution), consulting fees and honoraria for lectures from Alnylam and Sobi, support for attending meetings from Chiesi, and participated on a Data Safety Monitoring Board or Advisory Board for Alnylam. Patrick Stordeur received honoraria for lectures from Alexion Pharma Belgium and support for attending meetings from Thermofisher. Johan Vande Walle received consulting fees from Ferring, Astellas, Bayer, and Alexion (through his institution); payment for lectures from Ferring, Bayer, and Alexion (through his institution); payment for expert testimony from Ferring (through his institution); support for attending meetings from Alexion (through his institution). He participated on a Data Safety Monitoring Board or Advisory Board for Bayer (through his institution) and has a leadership or fiduciary role in other board, society, committee or advocacy group for the International Pediatric Nephrology Association and Connect 4 Children (through his institution). Tess Van Meerhaeghe, Eric Goffin, Brigitte Adams and Stefan Van Cauwelaert have nothing to disclose. Ethical approval: The study was approved by the relevant ethics committee at every center. Human and animal rights: The study was conducted in accordance with the Declaration of Helsinki. The protocol was reviewed and approved by the relevant ethics committee at every center, and all participants or their legal representatives provided written informed consent for enrollment. No animals were involved in this research. Informed consent and consent to participate: All participants or their legal representatives provided written informed consent for enrollment.

Figures

Fig. 1
Fig. 1
Cumulative frequency of aHUS by age at disease onset and by gender. aHUS atypical hemolytic uremic syndrome
Fig. 2
Fig. 2
Cumulative Kaplan–Meier estimates for KF-free survival in adults and children with aHUS (a) and by gender (b). KF kidney failure; aHUS atypical hemolytic uremic syndrome
See this image and copyright information in PMC

References

    1. Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Frémeaux-Bacchi V (2016) An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 31:15–39. 10.1007/s00467-015-3076-8 - DOI - PubMed
    1. Fakhouri F, Schwotzer N, Frémeaux-Bacchi V (2023) How i diagnose and treat atypical hemolytic uremic syndrome. Blood 141:984–995. 10.1182/blood.2022017860 - DOI - PubMed
    1. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschênes G, Lebranchu Y, Zuber J, Loirat C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562. 10.2215/cjn.04760512 - DOI - PMC - PubMed
    1. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859. 10.2215/cjn.02210310 - DOI - PMC - PubMed
    1. Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B, André JL, Takagi N, Cheong HI, Hari P, Le Quintrec M, Niaudet P, Loirat C, Fridman WH, Frémeaux-Bacchi V (2010) Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol 21:2180–2187. 10.1681/asn.2010030315 - DOI - PMC - PubMed

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