C3 Glomerulonephritis: From Diagnosis to Management in a Unique Patient Case

• Author(s): Castro, Pedro ; Oliveira, Nuno ; Alves, Rui
• Date: 2025
• Origin: Portuguese Kidney Journal (PKJ)
• Subject(s): Complement C3; Glomerulonephritis; Glomerulonephritis, Membranoproliferative
• Document Type: Journal article
• Language: English

Description

C3 glomerulopathies (C3G) are ultra -rare diseases driven by dysregulation of the alternative pathway in the complement system, leading to glomerular C3 deposition and inflammation. C3G includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), both associated with progression to end -stage renal disease (ESRD). This report presents a C3GN case, highlighting diagnostic and therapeutic complexities. A 19 -year -old male with recurrent macroscopic hematuria triggered by respiratory infections was initially managed for suspected IgA nephropathy. Follow -up revealed persistent low serum C3 levels, prompting a kidney biopsy that confirmed C3GN with a membranoproliferative pattern and dominant C3 deposits. Genetic testing revealed a C3 mutation and positive anti -Factor H antibodies. Despite treatment with renin -angiotensin -aldosterone system blockade, steroids, and mycophenolate mofetil (MMF), the patient’s proteinuria fluctuated, requiring adjustments in immunosuppressive therapy. C3GN can mimic other glomerulonephritides such as IgA nephropathy and atypical hemolytic uremic syndrome (aHUS). Accurate diagnosis relies on kidney biopsy findings and complement studies; genetic testing can provide critical insights. While available therapies, including immunosuppressants and complement inhibitors, offer partial benefit, C3GN often progresses, underscoring the need for novel, more effective treatments. This case illustrates the diagnostic challenges of C3GN in patients with hypocomplementemia and recurrent hematuria. It emphasizes the importance of targeted research into complement therapies to potentially improve outcomes for C3G.