What is the management of glomerulonephritis?

Management of Glomerulonephritis

The management of glomerulonephritis should include both disease-specific immunosuppressive therapy based on the specific type of glomerulonephritis and supportive care measures to control hypertension, edema, and proteinuria. 1

Diagnosis and Classification

Before initiating treatment, proper diagnosis is essential:

• Kidney biopsy is the gold standard for diagnosis and classification of glomerulonephritis
• Evaluate urine sediment, proteinuria, and kidney function
• Screen for relevant infections (tuberculosis, hepatitis B/C, HIV, syphilis)
• Classify based on pathogenic mechanism rather than histological pattern:
  • Immune-complex glomerulonephritis
  • Pauci-immune (ANCA-associated) glomerulonephritis
  • Anti-glomerular basement membrane glomerulonephritis
  • C3 glomerulopathy
  • Monoclonal immunoglobulin-associated glomerulonephritis

Immunosuppressive Therapy

Pauci-immune Glomerulonephritis

• Initial therapy: Cyclophosphamide and corticosteroids 1
  • IV pulse methylprednisolone (500-1000 mg daily for 3 days)
  • Followed by oral prednisone 1 mg/kg/day (maximum 80 mg)
  • Taper prednisone over 3-6 months
  • Cyclophosphamide: oral (2 mg/kg/day) or IV pulse (15 mg/kg every 2-3 weeks) for 3-6 months
• Alternative: Rituximab (375 mg/m² weekly for 4 weeks or 1000 mg on days 1 and 15)
• Maintenance therapy: Azathioprine (1-2 mg/kg/day) for at least 18 months

Minimal Change Disease (MCD)

• Initial therapy: High-dose corticosteroids for 4-16 weeks 2
• For steroid resistance/intolerance: Cyclophosphamide or calcineurin inhibitors
• For relapse: Treat as per initial episode

Focal Segmental Glomerulosclerosis (FSGS)

• Initial therapy: High-dose corticosteroids for 4-16 weeks, continued until remission 2
• After remission: Taper steroids slowly over 6 months
• For steroid resistance: Calcineurin inhibitors

Membranoproliferative Glomerulonephritis (MPGN)

• For idiopathic MPGN with nephrotic syndrome: Cyclophosphamide or mycophenolate mofetil plus low-dose corticosteroids 1
• Therapy should be limited to less than 6 months

Infection-Related Glomerulonephritis

• Treat the underlying infection 2
• For post-streptococcal GN: Penicillin or erythromycin for 10 days
• For infective endocarditis: Appropriate antibiotics for 4-6 weeks
• Immunosuppression generally not indicated unless severe crescentic GN

Supportive Care Measures

Hypertension Management

• ACE inhibitors or ARBs at maximally tolerated doses 1
• Target systolic BP <120 mmHg in most adult patients
• Monitor for adverse effects (hyponatremia, hypokalemia, GFR reduction)

Edema Management

• Dietary sodium restriction (<2.0 g/day)
• Diuretics (loop or thiazide) as first-line therapy
• Monitor for volume depletion and electrolyte abnormalities

Proteinuria Reduction

• ACE inhibitors or ARBs for patients with proteinuria
• Monitor proteinuria as a surrogate endpoint for treatment response

Nutrition

• Protein restriction based on proteinuria level and kidney function:
  • 0.8-1 g/kg/day for nephrotic-range proteinuria
  • 0.8 g/kg/day for eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria
• Prefer plant-based protein sources
• Target caloric intake: 35 kcal/kg/day (30-35 kcal/kg/day if eGFR <60)

Infection Prevention

• Pneumococcal and influenza vaccination
• Herpes zoster vaccination (Shingrix)
• Prophylactic trimethoprim-sulfamethoxazole for patients on high-dose immunosuppression

Special Considerations

Hepatitis-Associated Glomerulonephritis

• For hepatitis B: Nucleoside analogues (tenofovir or entecavir)
• For hepatitis C: Antiviral treatment based on kidney function

Relapse Management

• Severe relapse: Treat according to same guidelines as initial therapy
• Non-severe relapse: Reinstitute or increase immunosuppressive therapy

Resistant Disease

• Add rituximab for disease resistant to cyclophosphamide and corticosteroids
• Consider intravenous immunoglobulin or plasmapheresis as alternatives

Monitoring

• Regular assessment of renal function tests, urinalysis, and relevant serologies
• Monitor for disease activity in other organ systems
• Watch for ≥40% decline in eGFR from baseline over 2-3 years (suggests progression to kidney failure)

Common Pitfalls and Caveats

• Avoid extrapolating pediatric literature to adults as response to therapy is more variable in adults 2
• Be vigilant for side effects of immunosuppressive therapy
• Consider cardiovascular risk reduction in all patients with glomerulonephritis
• Differentiate between idiopathic and secondary causes before initiating immunosuppression
• Recognize that some forms of glomerulonephritis (like IgA-dominant post-infectious GN) may worsen with corticosteroid treatment 2