C3 Glomerulonephritis Presenting as Thrombotic Microangiopathy: A Case Report of Rare and Aggressive Phenotype
Sumit Tyagi and Bipasa Kar*
ABSTRACT
Background: C3 glomerulonephritis (C3GN) is a rare complement-mediated glomerular disease caused by dysregulation of the alternative complement pathway. Although C3GN and thrombotic microangiopathy are distinct entities, complement overactivation may produce overlapping clinical features and create diagnostic challenges.
Case Presentation: A 37-year-old man presented with uremic symptoms, dyspnoea, altered sensorium, severe hypertension, anaemia, thrombocytopenia, and grade IV hypertensive retinopathy. Laboratory investigations revealed severe kidney dysfunction, elevated lactate dehydrogenase, markedly reduced haptoglobin, hypocomplementemia with low C3 and normal C4, proteinuria, and microscopic haematuria. However, peripheral blood smear showed no schistocytes, the reticulocyte count was 1.5%, direct Coombs testing was negative, and ADAMTS13 activity was normal. Anti-factor H antibody was also negative. Kidney biopsy demonstrated a membranoproliferative pattern with prominent lobular accentuation, diffuse endocapillary proliferation, leukocytic infiltration, and double-contour formation of the glomerular capillary walls. Approximately 50% interstitial fibrosis and tubular atrophy were present, along with tubular hemosiderin deposition. Immunofluorescence showed granular C3 deposition along the glomerular capillary loops, with negative staining for immunoglobulins, C1q, and light chains. These findings established the diagnosis of C3GN with a membranoproliferative pattern and secondary hemosiderosis. Haemodialysis was initiated because of uremic symptoms and volume overload.
Conclusion: This case highlights an aggressive C3GN presentation with a clinical phenotype suggestive of TMA, despite the absence of schistocytes and normal ADAMTS13 activity. The combination of severe hypertension, thrombocytopenia, biochemical evidence of haemolysis, hypocomplementemia, and C3-dominant renal deposits underscores the importance of integrating clinical, haematological, complement, and histopathological findings. Early recognition of this atypical presentation may help distinguish C3GN from primary TMA and guide appropriate management.
