What is the treatment for Rapidly Progressive Glomerulonephritis (RPGN)?

Treatment of Rapidly Progressive Glomerulonephritis (RPGN)

The treatment for RPGN should be initiated promptly with induction therapy consisting of glucocorticoids plus either cyclophosphamide or rituximab, with IV pulse methylprednisolone (500-1000 mg daily for 3 days) followed by oral prednisone (initially 1 mg/kg/day, maximum 60-80 mg). 1

Classification and Diagnosis

RPGN is a severe clinical syndrome characterized by rapid decline in kidney function over days to weeks that leads to irreversible kidney failure if not diagnosed and treated promptly. It can be classified into three major categories:

1. Anti-GBM antibody disease (Type I)
2. Immune complex-mediated (Type II)
3. Pauci-immune (Type III) - most common form (>50% of cases) 1

Diagnostic workup should include:

• Urinalysis with microscopy (look for RBC casts and dysmorphic RBCs)
• Serum creatinine and eGFR
• 24-hour urine protein or protein-to-creatinine ratio
• Autoimmune serologies:
  • ANCA (anti-MPO and anti-PR3)
  • Anti-GBM antibodies
  • ANA and anti-dsDNA
  • Complement levels (C3, C4)
• Kidney biopsy (gold standard) 1

Treatment Protocol

Immediate Management

• Do not delay treatment while waiting for kidney biopsy results if clinical presentation strongly suggests RPGN and serologies are positive for ANCA or anti-GBM antibodies 1

Induction Therapy

1. Glucocorticoids:

   • IV pulse methylprednisolone 500-1000 mg daily for 3 days
   • Followed by oral prednisone 1 mg/kg/day (maximum 60-80 mg)

2. Plus one of the following:

   • Cyclophosphamide (oral or IV)
   • Rituximab 1

3. Plasma exchange should be considered for:

   • Anti-GBM disease
   • Severe ANCA-associated vasculitis with pulmonary hemorrhage
   • Dialysis-dependent patients 1, 2

Maintenance Therapy

• Rituximab or azathioprine
• Low-dose glucocorticoids
• Continue for at least 18 months 1

Special Considerations

Elderly Patients

• Elderly patients respond to immunosuppressive therapy similarly to younger patients but have higher risk of adverse events
• Treatment needs to be individualized with careful consideration of risks 3
• Age is an independent negative risk factor for both death and end-stage renal disease in ANCA-associated vasculitis 3

Monitoring

• Regular assessment of kidney function
• Urinalysis to monitor disease activity
• Complete blood count to monitor for treatment toxicity
• ANCA titers (though treatment decisions should not be based solely on ANCA titers) 1

Prognostic Factors

• Severity of kidney dysfunction at presentation
• Percentage of crescents on biopsy
• Underlying cause
• Promptness of treatment initiation 1

Supportive Care

• Blood pressure management with ACEi or ARB (if proteinuria >0.5 g/d)
• Cardiovascular risk assessment and management
• Lifestyle advice including dietary sodium restriction, smoking cessation, weight control, and exercise 4

Early diagnosis and prompt treatment are critical factors in determining outcomes in RPGN. Without treatment, approximately 90% of cases lead to renal failure or death, but with appropriate therapy, the condition is potentially reversible 5.