What are the latest Indian guidelines for treating Rapidly Progressive Glomerulonephritis (RPGN)?

Latest Indian Guidelines for Treating Rapidly Progressive Glomerulonephritis (RPGN)

The latest Indian guidelines for treating Rapidly Progressive Glomerulonephritis (RPGN) follow the KDIGO 2021 guidelines, which recommend immediate initiation of immunosuppressive therapy with cyclophosphamide or rituximab plus corticosteroids, without waiting for kidney biopsy confirmation if clinical presentation and serologies strongly suggest the diagnosis. 1

Diagnostic Approach

Initial Evaluation

• Assess for rapid decline in kidney function with:
  • Positive urine dipstick for protein and blood
  • Urine sediment showing glomerular hematuria and/or pyuria without infection
  • Evaluate for extrarenal manifestations
  • Obtain autoimmune serologies (ANCA, ANA, anti-GBM antibodies, complement)
  • Exclude infection before immunosuppression
  • Obtain kidney biopsy when feasible 1

Biopsy Strategy

• Do not delay treatment waiting for biopsy if clinical presentation is compatible with small-vessel vasculitis and MPO or PR3-ANCA serology is positive
• Same principle applies for anti-GBM antibody GN or lupus nephritis
• Perform biopsy soon after starting treatment when feasible 1

Treatment Recommendations by Etiology

ANCA-Associated Vasculitis (Most Common Cause of RPGN)

1. Induction Therapy:

   • Cyclophosphamide or rituximab plus corticosteroids 1
   • For severe GN (SCr >4 mg/dl [354 μmol/l]), consider combination of two intravenous pulses of cyclophosphamide with rituximab 1
   • High-dose glucocorticoids typically starting with IV pulse methylprednisolone

2. Maintenance Therapy:

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

3. Plasma Exchange:

   • Not recommended routinely in AAV
   • Use if AAV overlaps with anti-GBM antibody GN 1

Anti-GBM Disease (Goodpasture Syndrome)

1. Immediate Treatment:

   • Plasma exchange until anti-GBM antibodies are undetectable 2
   • IV pulse methylprednisolone followed by oral prednisone taper over at least 6 months 2
   • Oral cyclophosphamide (2-3 mg/kg daily) for approximately 3 months 2

2. Special Considerations:

   • All patients with pulmonary hemorrhage should receive plasmapheresis regardless of renal status 2
   • Patients who are dialysis-dependent with 100% crescents on biopsy and no pulmonary hemorrhage have poor renal prognosis (only ~8% recovery rate) 2
   • Double-positive patients (anti-GBM and ANCA positive) should receive initial treatment as for anti-GBM disease, then maintenance as for AAV 2

3. Post-Treatment:

   • No maintenance immunosuppression for isolated anti-GBM disease (relapse rate <5%) 2
   • Monitor for at least 2 years after diagnosis 2
   • Defer kidney transplantation until anti-GBM antibodies have been undetectable for at least 6 months 2

Lupus Nephritis with RPGN

• Follow standard lupus nephritis protocols with aggressive initial immunosuppression 1
• Do not delay treatment waiting for biopsy confirmation if clinical presentation strongly suggests the diagnosis 1

Treatment Considerations

Corticosteroids

• Begin with IV pulse methylprednisolone (typically 1g daily for 3 consecutive days) 3
• Follow with oral prednisone, tapering over at least 6 months 2

Cyclophosphamide

• Oral dosing: 2-3 mg/kg daily for approximately 3 months
• Adjust dose for reduced GFR and older age
• Provide pneumocystis prophylaxis with trimethoprim-sulfamethoxazole until cyclophosphamide is complete and prednisone dose is <20 mg daily 2

Rituximab

• Consider for patients with contraindications to cyclophosphamide
• May be used in combination with cyclophosphamide for severe disease
• Increasingly used for refractory cases 4

Plasmapheresis

• Essential for anti-GBM disease
• Indicated for AAV with pulmonary hemorrhage or when overlapping with anti-GBM disease
• Most beneficial when initiated early in disease course 5

Common Pitfalls and Caveats

1. Delay in Treatment:

   • Do not wait for biopsy confirmation if clinical suspicion is high; early treatment is crucial for preserving kidney function 1

2. Infection Risk:

   • Always exclude infection before initiating immunosuppression 1
   • Monitor closely for opportunistic infections during treatment 2

3. Relapse Risk Factors:

   • Diagnosis of granulomatosis with polyangiitis
   • PR3-ANCA positivity
   • ANCA positivity at the end of induction
   • History of previous relapse
   • Lower cyclophosphamide exposure
   • Glucocorticoid withdrawal 1

4. Transplantation Timing:

   • For anti-GBM disease: wait until antibodies are undetectable for at least 6 months
   • For AAV: persistent ANCA positivity should not delay kidney transplantation 1

By following these guidelines, the mortality and morbidity associated with RPGN can be significantly reduced, and kidney function may be preserved in many patients when treatment is initiated promptly.