Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities.

Publisher: Springer International Country of Publication: Germany NLM ID: 8708728 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-198X (Electronic) Linking ISSN: 0931041X NLM ISO Abbreviation: Pediatr Nephrol Subsets: MEDLINE

Publication: Berlin : Springer International
Original Publication: Berlin : Springer International, c1987-

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

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 (clinicaltrials.gov 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.
(© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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R01 DK076690 United States DK NIDDK NIH HHS

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

0 (Complement Inactivating Agents)
0 (Complement C3)

Date Created: 20230921 Date Completed: 20240318 Latest Revision: 20241019

20241019

10.1007/s00467-023-06120-8

37733095