C3 Glomerulonephritis

C3 glomerulonephritis is a rare form of glomerulonephritis characterized by the abnormal activation of the complement system, particularly the alternative pathway in the fluid phase. This leads to dominant excessive deposition of C3 protein in the glomeruli, causing inflammation and damage to the kidneys.

• Hematuria (blood in the urine)
• Proteinuria (excessive protein in the urine)
• Edema (swelling), particularly around the eyes and ankles
• Hypertension (high blood pressure)
• Reduced urine output
• Fatigue and malaise

The diagnosis is defined by renal biopsy pathology: a predominance of C3 deposition on immunofluorescence with electron microscopy permitting disease sub-classification. Complement dysregulation underlies the observed pathology, a causal relationship that is supported by well described studies of genetic and acquired drivers of disease.

• Corticosteroids: In some cases, corticosteroids (such as prednisone) may be prescribed to reduce inflammation in the kidneys and manage proteinuria.
• Immunosuppressive drugs: Immunosuppressive medications like cyclophosphamide, mycophenolate mofetil, or rituximab may be used in combination with or as an alternative to corticosteroids, particularly in cases of more severe or refractory C3GN.

One of the key complement inhibitors used in the treatment of complement-mediated glomerulonephritis is Eculizumab, a monoclonal antibody that specifically inhibits the C5 component of the complement system.

• By blocking C5, Eculizumab prevents the formation of the membrane attack complex (MAC), which is responsible for cell damage and inflammation in many complement-mediated kidney diseases.  
• Eculizumab is not effective in all diseases with a dysfunction of the complement system. The variable results with eculizumab in C3GN suggest that more proximal alternative complement pathway blockade may be needed to achieve disease control in C3GN.
• Avacopan, an oral C5aR inhibitor, Iptacopan, a small molecule oral factor B inhibitor as well Pegectacoplan, an inhibitor of C3 shown promising results in clinical trials conducted in patients with C3GN.

Please Note: 
The field of complement-mediated kidney diseases is evolving rapidly, and ongoing research is aimed at developing new therapies and optimizing treatment strategies. Therefore, it's essential for patients and healthcare providers to stay informed about the latest developments in the field of complement-mediated glomerulonephritis and to discuss the most appropriate treatment options based on the individual patient's needs.

Controlling blood pressure is crucial to protect kidney function. Medications like angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) may be prescribed.

Reducing dietary sodium (salt) intake may help manage fluid retention and hypertension. Additionally, protein intake may be adjusted based on kidney function and proteinuria levels.

If C3GN is secondary to another condition, such as an infection or autoimmune disease, addressing the underlying cause is essential for managing the kidney disorder.