Advancing Treatment for C3G; Targeting the Complement System for Personalized Kidney Care - Episode 6
Strength in Numbers: Raising Awareness of C3G and Other Rare Diseases
Panelists discuss how educating physicians and patients about C3 glomerulopathy (C3G) presents unique challenges due to its rarity, complexity, and the critical role of renal pathologists in diagnosis while emphasizing the growing importance of understanding the complement system as new targeted therapies emerge.
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A Clinical Summary of C3G
Overview
C3G is an ultra-rare, complex kidney disease characterized by predominant C3 deposition in the glomeruli due to dysregulation of the alternative complement pathway. C3G serves as an umbrella term that includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN).
Diagnostic Challenges
- C3G patients are typically complex and challenging to diagnose
- Clinical presentation is often nonspecific and variable
- Renal pathology is crucial for diagnosis, requiring specialized expertise
- Hypocomplementemia is not universally present (normal complement levels don’t rule out C3G)
- Can be difficult to distinguish from post-infectious glomerulonephritis, particularly in pediatric populations
Key Diagnostic Steps
- Renal biopsy: Essential for diagnosis; collaboration with experienced renal pathologists is critical
- Etiology investigation:
- Monoclonal gammopathies (particularly in patients aged >50 years)
- Genetic testing for complement pathway mutations
- Autoantibody testing (C3 nephritic factor, anti-factor H)
Educational Needs
- Increasing recognition of complement’s role in glomerular diseases
- Training on appropriate workup for suspected C3G
- Familiarity with the complement system, particularly the alternative pathway
- Awareness that C3G can present differently in pediatric vs adult populations
Treatment Considerations
- New complement-targeting therapies offer promising treatment options
- Understanding the underlying mechanism is essential for appropriate therapy selection
- Different management strategies may be needed for pediatric vs adult patients
- Implications for kidney transplantation and potential living donors
Follow-Up
- Patients with ongoing proteinuria, active urinary sediment, or persistent symptoms should be evaluated for C3G even after initial diagnosis of another condition
- Long-term monitoring is essential as the disease can progress slowly
Patient/Family Education
- Patients and families often become the experts on their condition
- Primary care physicians may need education from specialists to provide appropriate care
Clear explanations of complement dysregulation help patients understand their disease and treatment options
