Long-term Eculizumab Treatment Failure in C3 Glomerulonephritis: two case reports

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ID: 316469
2026
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Abstract
Abstract C3 glomerulonephritis (C3GN) is a rare kidney disease driven by dysregulation of the alternative complement pathway (AP). We report two challenging cases of patients with C3GN in whom various immunosuppressant (IS) therapies have failed to achieve complete remission, prompting treatment with eculizumab, an anti-C5 humanized monoclonal antibody that inhibits the terminal complement pathway. Although transient improvement in kidney function was observed, both patients eventually experienced worsening renal parameters, with increasing proteinuria and hematuria, culminating in progression to end-stage kidney disease (ESKD). Repeated kidney biopsies following eculizumab therapy demonstrated persistent, granular mesangial and capillary wall C3 (3+) staining on immunofluorescence (IF) studies, indicating ongoing complement activation upstream of the C5 blockade and the perpetuation of C3 deposits in the glomeruli. These cases underscore the limited efficacy of terminal complement inhibition in halting disease progression in C3GN.
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Authors Dalia Zubidat, María José Soler, Anila Cara, Sanjeev Sethi, Gerald B Appel, Dominick Santoriello, Fernanda Dos Santos, Fernando C Fervenza
Journal clinical kidney journal
Year 2026
DOI
10.1093/ckj/sfag189
URL
https://doi.org/10.1093/ckj/sfag189
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