Abstract
Background
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9).
Case-diagnosis/treatment
We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses.
Conclusions
Not every patient with aHUS and uncontrolled complement activation shows optimal therapeutic response to eculizumab with the recommended or even increased dosing regimen. Reliable outcome measures to determine the efficacy of treatment have to be defined.
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Acknowledgements
We thank Marina Noris and Miriam Galbusera from IRCCS—Mario Negri Institute for Pharmacological Research in Bergamo for their assistance in investigating the ex vivo serum-induced endothelial C5b-9 deposits in our patient.
Conflict of interests
C.B. is an employee of Bioscientia/Sonic Healthcare.
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Schalk, G., Kirschfink, M., Wehling, C. et al. A complicated case of atypical hemolytic uremic syndrome with frequent relapses under eculizumab. Pediatr Nephrol 30, 1039–1042 (2015). https://doi.org/10.1007/s00467-015-3078-6
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DOI: https://doi.org/10.1007/s00467-015-3078-6