New Anticomplement Drugs in Nephrology: Mechanism and Indication

Abstract – Background: The complement system is a key component of innate immunity, critical for pathogen defense, inflammation, and immune regulation. Dysregulation or overactivation of complement pathways contributes to the pathogenesis of numerous kidney diseases, including atypical hemolytic uremic syndrome, C3 glomerulopathy, membranous nephropathy, systemic lupus erythematosus, antiphospholipid antibody syndrome, ANCA-associated vasculitis, diabetic nephropathy, and focal segmental glomerulosclerosis. In these conditions, uncontrolled complement activation drives renal inflammation, microvascular injury, and fibrosis. Summary: Recent advances in complement biology have enabled the development of targeted anticomplement therapies. These include C5 inhibitors (eculizumab, ravulizumab, crovalimab, nomacopan), C3 inhibitors (pegcetacoplan), factor B and D inhibitors (iptacopan, danicopan, vemircopan), C5a receptor antagonists (avacopan), and MASP-2 inhibitors (narsoplimab). This review outlines their mechanisms of action, current clinical indications, and evidence from clinical trials and real-world experience. It also addresses challenges such as safety, cost, and optimization of treatment strategies, while considering future directions in biomarker-driven, personalized approaches. Key Messages: Anticomplement therapies represent a transformative advance in nephrology, offering targeted interventions that can improve outcomes for patients with complement-mediated kidney diseases. Their strategic use may reduce disease progression, manage inflammation, and mitigate organ damage, highlighting the potential of personalized treatment approaches in complement-driven renal disorders.