A complicated case of atypical hemolytic uremic syndrome with frequent relapses under eculizumab

作者：Schalk Gesa^*; Kirschfink Michael; Wehling Cyrill; Gastoldi Sara; Bergmann Carsten; Hoppe Bernd; Weber Lutz T

来源：Pediatric Nephrology, 2015, 30(6): 1039-1042.

DOI：10.1007/s00467-015-3078-6

• Complement-associated renal disease
• Drug level
• Eculizumab
• Genetic disease
• Long-term treatment
• Terminal complement complex

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).
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.
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.

• 出版日期2015-6