What is the current guideline for treatment of pauci-immune (few immune cells) glomerulonephritis?

Treatment Guidelines for Pauci-Immune Glomerulonephritis

For pauci-immune glomerulonephritis, the current guideline recommends initial immunosuppression with cyclophosphamide and corticosteroids, followed by maintenance therapy with azathioprine for at least 18 months. 1

Initial Diagnosis and Classification

• Pauci-immune glomerulonephritis (PICGN) is characterized by:

  • Few or no immune deposits on immunofluorescence
  • Fibrinoid necrosis and crescent formation on light microscopy
  • Majority (80-90%) are ANCA-positive 2, 3
  • Can be renal-limited or part of systemic vasculitis (ANCA-associated vasculitis)

• Three clinical phenotypes:

  • Microscopic polyangiitis (MPA)
  • Granulomatosis with polyangiitis (GPA, formerly Wegener's)
  • Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss)

Induction Therapy

For New-Onset Disease:

1. Corticosteroids:

   • Begin with IV pulse methylprednisolone (500-1000 mg daily for 3 days)
   • Follow with oral prednisone 1 mg/kg/day (maximum 80 mg) 1
   • Gradually taper over 3-6 months

2. Cyclophosphamide (CYC) - choose ONE regimen:

   • Oral: 2 mg/kg/day (maximum 200 mg/day) for 3-6 months 1
   • IV pulse: 15 mg/kg every 2-3 weeks (adjust for age and renal function)
   • Continue until remission, typically 3-6 months

3. Alternative to cyclophosphamide:

   • Rituximab: 375 mg/m² weekly for 4 weeks or 1000 mg on days 1 and 15
   • Consider for patients with contraindications to cyclophosphamide 1, 4

4. Adjunctive therapy:

   • Plasmapheresis: Consider for patients with pulmonary hemorrhage or severe renal dysfunction (creatinine >5.7 mg/dL) 1
   • Trimethoprim-sulfamethoxazole: For upper respiratory disease and Pneumocystis pneumonia prophylaxis 1, 4

Maintenance Therapy

1. Duration:

   • Continue for at least 18 months after achieving remission 1
   • No maintenance needed for dialysis-dependent patients without extrarenal manifestations 1

2. First-line maintenance:

   • Azathioprine: 1-2 mg/kg/day orally 1

3. Alternatives if intolerant to azathioprine:

   • Mycophenolate mofetil (MMF): Up to 1 g twice daily 1
   • Methotrexate: Initially 0.3 mg/kg/week (maximum 25 mg/week) - avoid if GFR <60 ml/min/1.73m² 1

4. NOT recommended:

   • Etanercept is specifically not recommended as adjunctive therapy 1

Treatment of Relapses

• Severe relapse (life- or organ-threatening):

  • Treat according to the same guidelines as initial therapy 1

• Non-severe relapse:

  • Reinstitute immunosuppressive therapy or increase intensity
  • Consider agents other than cyclophosphamide
  • Increase corticosteroid dose with or without azathioprine/MMF 1

Treatment-Resistant Disease

For disease resistant to cyclophosphamide and corticosteroids:

1. First choice: Add rituximab 1
2. Alternatives: Consider intravenous immunoglobulin or plasmapheresis 1

Special Considerations

• ANCA monitoring: Do not change immunosuppression based solely on ANCA titer changes 1

• Kidney transplantation:

  • Delay until patients are in complete extrarenal remission for 12 months
  • ANCA positivity alone should not delay transplantation if in complete remission 1

• ANCA-negative PICGN:

  • Consider underlying infections or malignancies 5
  • Treatment approach similar to ANCA-positive disease for primary forms
  • Higher mortality rates despite immunosuppressive treatment 5

Monitoring and Follow-up

• Regular monitoring of:
  • Renal function tests
  • Urinalysis for hematuria and proteinuria
  • ANCA levels (though not for treatment decisions)
  • Signs of disease activity in other organ systems
  • Drug toxicity

Prognosis

• Untreated ANCA-associated PICGN has poor prognosis 2
• With treatment, complete long-term remission occurs in 70-75% of patients 2
• Relapse occurs in >25% of cases within 18 months after stopping therapy 2
• Infection is a major cause of death in the first year after diagnosis 3

Common Pitfalls to Avoid

1. Delaying treatment while waiting for complete diagnostic workup - begin treatment promptly if diagnosis is strongly suspected
2. Inadequate initial immunosuppression leading to irreversible organ damage
3. Excessive immunosuppression leading to serious infections
4. Stopping maintenance therapy too early, increasing risk of relapse
5. Changing treatment based solely on ANCA titer fluctuations
6. Failing to provide prophylaxis against Pneumocystis pneumonia during immunosuppressive therapy

Remember that early diagnosis and prompt initiation of appropriate immunosuppressive therapy are crucial to prevent irreversible kidney damage and improve patient outcomes.