C3 Glomerulonephritis Associated With Anti-complement Factor B Antibodies Following Anti-cancer Treatment With...

Complement 3 (C3) glomerulonephritis (C3GN) is a rare diagnosis based on predominant C3 glomerular deposition relative to other immune reactants on kidney biopsy. It is typically a membranoproliferative glomerulonephritis with or without crescents. Causes are heterogenous, ranging from genetic defects to acquired autoimmunity against complement factors. A 78-year-old male presented with stage 3 acute kidney injury and microscopic hematuria on the background of a diarrheal illness, urinary tract infection and 2 years treatment with pembrolizumab for metastatic bladder cancer. Kidney histology revealed a crescentic C3GN with intratubular red blood cell casts. Complement analysis showed an acquired autoimmunity with circulating factor B antibodies. Despite treatment with corticosteroids, plasma exchange, cyclophosphamide and eculizumab he remained dialysis-dependent. This is an unusually aggressive case of C3GN. PD-1 inhibitors, such as pembrolizumab, are known to predispose to loss of tolerance and generation of autoantibodies. In this case, factor B autoantibodies were detected in association with C3GN.