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

Treatment of Rapidly Progressive Glomerulonephritis (RPGN)

For patients with rapidly progressive crescentic glomerulonephritis, treatment should consist of high-dose glucocorticoids and cyclophosphamide, initiated promptly without waiting for kidney biopsy results if clinical suspicion is high and serologies are positive. 1, 2

Classification and Initial Evaluation

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)

Essential Laboratory Workup:

• Serum creatinine and eGFR
• Urinalysis with microscopy (look for RBC casts, dysmorphic RBCs)
• 24-hour urine protein or protein-to-creatinine ratio
• Autoimmune serologies:
  • ANCA (MPO and PR3)
  • Anti-GBM antibodies
  • ANA and anti-dsDNA
  • Complement levels (C3, C4)
• Hepatitis B and C serologies, HIV testing
• Serum protein electrophoresis

Treatment Algorithm

1. Induction Therapy (First-line treatment)

• High-dose glucocorticoids:
  • IV pulse methylprednisolone 500-1000 mg daily for 3 days
  • Followed by oral prednisone 1 mg/kg/day (maximum 60-80 mg)
• PLUS one of the following:
  • Cyclophosphamide (oral or IV)
  • Rituximab (for ANCA-associated RPGN)

2. Adjunctive Therapy

• Plasma exchange should be considered for:
  • Anti-GBM disease
  • ANCA-associated RPGN with pulmonary hemorrhage
  • RPGN with severe kidney dysfunction (creatinine >5.7 mg/dL)

3. Maintenance Therapy

• After 3-6 months of induction therapy:
  • Transition to rituximab or azathioprine
  • Taper glucocorticoids to low dose
  • Continue maintenance for at least 18 months

Special Considerations by RPGN Type

Anti-GBM Disease (Type I)

• Combination of plasma exchange, cyclophosphamide, and glucocorticoids
• Plasma exchange should be performed daily for 14 days or until anti-GBM antibodies are undetectable

Immune Complex-Mediated RPGN (Type II)

• Treatment depends on underlying cause:
  • For lupus nephritis: Cyclophosphamide or mycophenolate mofetil plus glucocorticoids
  • For IgA nephropathy with crescents: High-dose glucocorticoids and cyclophosphamide
  • For post-infectious GN: Treat underlying infection plus immunosuppression if severe

Pauci-immune RPGN (Type III)

• Cyclophosphamide or rituximab plus glucocorticoids
• Consider plasma exchange for severe disease

Monitoring and Prognosis

• Regular assessment of kidney function and urinalysis
• Complete blood count to monitor for treatment toxicity
• ANCA titers (though treatment decisions should not be based solely on ANCA titers)
• Prognosis depends on:
  • Severity of kidney dysfunction at presentation
  • Percentage of crescents on biopsy
  • Underlying cause
  • Promptness of treatment initiation

Important Caveats

• Do not delay treatment while waiting for kidney biopsy results if clinical presentation strongly suggests RPGN and serologies are positive 2
• For most patients with idiopathic immune complex GN presenting with eGFR <30 ml/min per 1.73 m², supportive care alone is recommended, except in cases with active necrotizing or crescentic GN 1
• Patients with IgA nephropathy who develop RPGN should be treated according to the guidelines for ANCA-associated vasculitis 1
• Early diagnosis and treatment are crucial for favorable outcomes, as untreated RPGN leads to renal or patient death in about 90% of cases 3

By following this treatment algorithm promptly, you can significantly improve outcomes in this potentially life-threatening condition.