Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities

Pediatr Nephrol. 2024 May;39(5):1387-1404. doi: 10.1007/s00467-023-06120-8. Epub 2023 Sep 21.


Historically, the complement system (classical, lectin, alternative, and terminal pathways) is known to play a crucial role in the etiopathogenesis of many kidney diseases. Direct or indirect activation in these settings is revealed by consumption of complement proteins at the serum level and kidney tissue deposition seen by immunofluorescence and electron microscopy. The advent of eculizumab has shown that complement inhibitors may improve the natural history of certain kidney diseases. Since then, the number of available therapeutic molecules and experimental studies on complement inhibition has increased exponentially. In our narrative review, we give a summary of the main complement inhibitors that have completed phase II and phase III studies or are currently used in adult and pediatric nephrology. The relevant full-text works, abstracts, and ongoing trials ( site) are discussed. Data and key clinical features are reported for eculizumab, ravulizumab, crovalimab, avacopan, danicopan, iptacopan, pegcetacoplan, and narsoplimab. Many of these molecules have been shown to be effective in reducing proteinuria and stabilizing kidney function in different complement-mediated kidney diseases. Thanks to their efficacy and target specificity, these novel drugs may radically improve the outcome of complement-mediated kidney diseases, contributing to an improvement in our understanding of their underlying pathophysiology.

Keywords: Avacopan; C3 glomerulopathy; Children; Complement; Eculizumab; Kidney diseases; aHUS.

Publication types

  • Review

MeSH terms

  • Adult
  • Atypical Hemolytic Uremic Syndrome* / drug therapy
  • Child
  • Complement Activation
  • Complement C3 / metabolism
  • Complement Inactivating Agents / pharmacology
  • Complement Inactivating Agents / therapeutic use
  • Glomerulonephritis, Membranoproliferative* / drug therapy
  • Humans
  • Kidney Diseases* / drug therapy


  • Complement Inactivating Agents
  • Complement C3