Treatment of Membranoproliferative Glomerulonephritis (MPGN)
The treatment of MPGN should be directed at the underlying cause, with immunomodulating therapy for immune complex-mediated disease and antiviral therapy for infection-associated cases, particularly HCV-related MPGN. 1, 2
Modern Classification of MPGN
MPGN is no longer considered a single disease entity but rather a pattern of injury with multiple etiologies that can be classified based on immunofluorescence findings:
- Immune complex-mediated MPGN (IC-MPGN): Positive for immunoglobulins with or without complement
- Complement-mediated MPGN (C3G): Negative for immunoglobulins but positive for complement
- Immunofluorescence-negative MPGN: Negative for both immunoglobulins and complement (suggests chronic thrombotic microangiopathy) 1
Diagnostic Approach
- Kidney biopsy with light microscopy, immunofluorescence, and electron microscopy is essential for diagnosis 2
- Comprehensive evaluation for underlying causes:
- Chronic infections (hepatitis B, hepatitis C, endocarditis)
- Autoimmune diseases (lupus, rheumatoid arthritis)
- Monoclonal gammopathies (especially in patients >50 years)
- Complement disorders 2
Treatment Algorithm
1. HCV-Associated MPGN
- First-line treatment: Direct-acting antiviral (DAA) therapy for viral eradication 1
- For severe/rapidly evolving disease:
- Begin with immunomodulating treatment (glucocorticoids, immunosuppressants, plasma exchange)
- Add antiviral therapy after stabilization 1
- For mild disease (mesangial glomerulonephritis pattern):
- DAA therapy alone is often sufficient 1
2. Immune Complex-Mediated MPGN (IC-MPGN)
Secondary to infections:
- Treat the underlying infection with appropriate antimicrobials 2
- No role for immunosuppression unless infection is controlled
Secondary to autoimmune diseases:
- Treat the underlying autoimmune condition with appropriate immunosuppression 2
Secondary to monoclonal gammopathies:
- Target the B cell or plasma cell clone responsible for monoclonal immunoglobulin production 1
Idiopathic IC-MPGN:
- Tailor therapy based on disease severity and histology
- For severe disease: Glucocorticoids and/or immunosuppressive agents
- Consider mycophenolate mofetil (MMF) for patients with significant impairment of kidney function 1
3. Complement-Mediated MPGN (C3G)
- Consider mycophenolate mofetil as first-line therapy
- Eculizumab may be considered in patients who fail to respond to MMF 1
- Evaluate for genetic complement disorders and consider targeted therapies
Prognostic Factors
Poor prognostic indicators include:
- Hematuria at presentation (risk factor 3.52)
- High urinary protein/creatinine ratio
- Low hemoglobin values 3
- Persistent hypocomplementemia 4
Special Considerations
- MPGN Type I appears to respond better to alternate-day prednisone regimens compared to Type III, with better preservation of GFR and fewer relapses 4
- Patients with HCV-associated MPGN may experience recurrence of nephrotic syndrome if antiviral therapy is discontinued 5
- Approximately 39% of patients achieve partial or complete remission with appropriate therapy 6
Supportive Care
- Blood pressure control
- Proteinuria management with ACE inhibitors or ARBs
- Monitor for progression of kidney disease
- Evaluate cardiovascular risk (leading cause of death in over 60% of cases) 1
Monitoring Response
- Regular assessment of kidney function (serum creatinine, eGFR)
- Quantification of proteinuria
- Complement levels (C3, C4)
- In HCV-related cases, monitor viral load 1, 2
The treatment approach should be adjusted based on the specific MPGN subtype, underlying etiology, and disease severity to optimize outcomes related to morbidity, mortality, and quality of life.