Background: C3 glomerulonephritis (C3GN) is a rare form of glomerulopathy that is characterized by predominant C3 deposits. Eculizumab, a humanized monoclonal C5 antibody, has recently emerged as a treatment option for C3GN. We report a C3GN patient successfully treated with eculizumab.
Case diagnosis/treatment: A 5-year-old boy who presented with proteinuria, hematuria, high ASO titers, and low C3 levels was initially diagnosed with post-streptococcal GN. His first kidney biopsy confirmed this diagnosis, but complement investigations identified three alternative pathway dysregulation factors: C3 nephritic factor, complement factor I heterozygous mutation (I398L), and anti-factor H autoantibodies (4,500 AU/ml). A second biopsy performed 11 months after initial presentation (nephrotic range proteinuria) showed a C3GN suggestive of isolated C3 deposits. Despite the use of intensive immunosuppressive therapy (rituximab, corticosteroids, mycophenolate), nephrotic-range proteinuria persisted and a third kidney biopsy showed the same C3GN pattern with more endocapillary proliferation. The serum C5b-9 level was elevated. Eculizumab was initiated and resulted in a significant decline of proteinuria (5.3 to 1.3 g/day) and an improvement in pathologic features. A transient interruption of eculizumab resulted in a rapid rise in proteinuria to 9.3 g/day, which decreased to 0.8 g/day after resumption of treatment.
Conclusions: The administration of anti-C5 antibodies may represent a valuable therapeutic option in patients with C3GN.