Use of complement C5-inhibitor eculizumab in patients with infection-associated hemolytic uremic syndrome - a case-series report.

Background: Hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI), remains a leading cause of pediatric AKI. The complement system has a crucial role in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and eculizumab (ECZ) was approved as standard of care for its treatment. The two widely characterized forms of infection-associated HUS are Shiga toxin-producing E. coli (STEC)-HUS and Streptococcus pneumoniae-associated (SP)-HUS. Extrarenal manifestations such as central nervous system (CNS) involvement occur approximately in 20% of the cases and are accompanied by higher mortality. Abnormalities of the alternative complement pathway may also contribute to the development of both STEC-HUS and SP-HUS, offering a potential treatment option for complement C5 inhibition. Beyond best supportive care as standard therapeutic approach, ECZ has been successfully used in both STEC-HUS and SP-HUS patients. We provide further support that early use of ECZ for infection-associated HUS with severe clinical manifestation and abnormal complement-activation profile may be an effective therapeutic approach.

Methods: We report on three children (median age: 2 years, range: 2-10 years) diagnosed with infection-associated HUS treated with complement C5-inhibitor ECZ. All three patients were treated with ECZ and had excellent outcome. We retrospectively analyzed the clinical course, laboratory data and outcome of children with infection-associated HUS treated with ECZ.

Conclusions: In accordance with previous observations ECZ is an efficacious therapeutic choice in severe HUS patients with multiorgan involvement. A detailed complement activation profile, especially sC5b-9, is useful to indicate ECZ administration.