Complement-Amplifying Conditions in Atypical Hemolytic Uremic Syndrome: A Canadian Case Series.

Thrombotic microangiopathies (TMAs) are systemic disorders that often affect the kidneys and encompass a heterogeneous group of conditions, including atypical hemolytic uremic syndrome (aHUS). The complement pathway is thought to play a crucial role in the pathogenesis of aHUS, and a favorable response can be obtained through complement C5 inhibition. There is emerging evidence to suggest that the same is also true for several other forms of TMA. The purpose of this series is to report cases of aHUS in which both an innate defect of the alternative complement pathway and a complement-amplifying condition were suspected. This case series describes 8 patients who were managed in Canadian tertiary centers for aHUS and who presented initially with complement-amplifying conditions. In all cases, aHUS was associated with organ dysfunction and in some, with an innate defect of the alternative complement pathway. The complement-amplifying conditions identified were diverse including immune disorders, pregnancy, and a These observations illustrate the seriousness of secondary aHUS. They also add to existing lines of evidence that the complement pathway is potentially involved in this condition and that it should be considered as a therapeutic target of interest under such circumstances. Les microangiopathies thrombotiques (MAT) sont des troubles systémiques qui affectent souvent les reins et qui englobent un groupe hétérogène d’affections, notamment le syndrome hémolytique et urémique atypique (SHUa). On pense que la voie du complément joue un rôle crucial dans la pathogenèse du SHUa et qu’une réponse favorable pourrait être obtenue par inhibition du complément C5. De nouvelles preuves suggèrent qu’il en serait de même pour plusieurs autres formes de MAT. Cette série vise à rapporter des cas de SHUa pour lesquels on soupçonnait à la fois une anomalie congénitale de la voie alterne du complément et une condition d’amplification du complément. Cette série décrit les cas de huit patients qui présentaient initialement des conditions d’amplification du complément et qui ont été pris en charge pour un SHUa dans des centres tertiaires canadiens. Dans tous les cas, le SHUa était associé à un dysfonctionnement d’organe et, dans certains cas, à une anomalie congénitale de la voie alterne du complément. Les conditions d’amplification du complément identifiées étaient diverses, notamment des troubles immunitaires, une grossesse et une infection à une shigatoxine. L’état des patients s’est rapidement amélioré après un traitement avec éculizumab ou des échanges plasmatiques. Ces observations illustrent la gravité du SHUa secondaire. Elles s’ajoutent aux preuves existantes qui suggèrent que la voie du complément est potentiellement impliquée dans cette pathologie et qu’elle devrait être considérée comme une cible thérapeutique d’intérêt dans de telles circonstances.

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Déclaration de conflit d'intérêts

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr C.J.P. has received advisory board honoraria from Alexion, Apellis, Octapharma, Sanofi, and Biocryst, and is site investigator for clinical trials sponsored by Alexion, Apellis, and Sanofi. Dr K.P. has received honoraria for speaking and consulting from Ablynx/Sanofi, Bioverativ/Sanofi, Shire/Takeda, and Alexion Pharmaceuticals. She participated in industry-sponsored clinical trials for Ablynx/Sanofi and Bioverativ/Sanofi. Dr J.G. has received honoraria from Alexion Canada for provision of continuing medical education activities and advisory board participation. Dr L.-P.G. has received honoraria from Alexion Pharma Canada and is participating in an Alexion-funded clinical trial. Dr P.I. has received support from the Canadian Institutes of Health Research and the Kidney Foundation of Canada. He has also received honoraria from Alexion Canada for advisory board participation. The results presented within this article have not been published previously in whole or in part.