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 succesfully 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. Case presentation: 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. Conclusion: 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.