Complement System Inhibitors in Nephrology: A Comprehensive Review

Background. The complement system plays a critical role in the pathogenesis of several kidney diseases. Dysregulation of complement activation, particularly of the alternative pathway, leads to kidney injury via thrombotic microangiopathy, immune complex deposition, and direct podocyte damage. Summary. Complement system inhibitors represent a paradigm shift in nephrology therapeutics, offering targeted treatment for diseases previously associated with poor outcomes. This review comprehensively examines the present landscape of complement inhibition in kidney disease, including established therapies and emerging agents. Terminal complement inhibitors (eculizumab and ravulizumab) have revolutionized the treatment of atypical haemolytic uremic syndrome, demonstrating remarkable improvements in renal outcomes and survival. Proximal pathway inhibitors targeting Factor B (Iptacopan) and C3 (pegcetacoplan) show promise in C3 glomerulopathy and IgA nephropathy, with recent phase 3 trials demonstrating significant proteinuria reduction. Additional applications include immune complex membranoproliferative glomerulonephritis and ANCA-associated vasculitis, in which complement activation contributes to disease pathogenesis. However, these agents present unique challenges, including infection risk, particularly meningococcal disease, cost considerations, and uncertainty regarding optimal treatment duration.