What is the treatment for IgA (Immunoglobulin A) vasculitis and IgA crescentic glomerulonephritis (GN)?

Treatment of IgA Vasculitis and IgA Crescentic Glomerulonephritis

For IgA crescentic glomerulonephritis, treatment with high-dose glucocorticoids plus cyclophosphamide is strongly recommended, analogous to the treatment approach used for ANCA-associated vasculitis. 1

Classification and Initial Assessment

IgA-related kidney diseases can present in different forms requiring distinct treatment approaches:

1. IgA Vasculitis (Henoch-Schönlein purpura) - Systemic small vessel vasculitis affecting skin, joints, gastrointestinal tract, and kidneys
2. IgA Nephropathy - Primary glomerular disease with mesangial IgA deposits
3. Crescentic IgA Glomerulonephritis - Severe form with >50% of glomeruli showing crescents and rapidly progressive renal deterioration

Key Assessment Parameters:

• Percentage of glomeruli with crescents on kidney biopsy
• Rate of renal function decline
• Degree of proteinuria
• Presence of hematuria
• Extrarenal manifestations (for IgA vasculitis)

Treatment Algorithm

1. Crescentic IgA Glomerulonephritis (>50% crescents)

First-line therapy:

• High-dose glucocorticoids plus cyclophosphamide, similar to ANCA vasculitis treatment 1
  • Intravenous methylprednisolone pulses (15 mg/kg for 3 days) followed by oral prednisone (1 mg/kg/day, tapered over months) 2
  • Cyclophosphamide (1.5-2.5 mg/kg/day orally) until plateau of response (typically 12-25 weeks) 3

Maintenance therapy:

• After induction, transition to azathioprine (1-2 mg/kg/day) with low-dose prednisone (5-7.5 mg/day) for 1-2 years 3

2. IgA Nephropathy with Persistent Proteinuria

Supportive care (cornerstone of management):

• ACE inhibitors or ARBs for proteinuria >0.5 g/day 4, 1
• Blood pressure targets:
  • <130/80 mmHg if proteinuria <1 g/day
  • <125/75 mmHg if proteinuria ≥1 g/day 4, 1
• Dietary sodium restriction (<2 g/day), weight normalization, smoking cessation 4

For persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care:

• If eGFR ≥50 ml/min/1.73m²: Add 6-month course of corticosteroids 1, 4
• Consider fish oil supplements as adjunctive therapy 1, 4

3. IgA Vasculitis with Renal Involvement

For children with HSP nephritis:

• Persistent proteinuria 0.5-1 g/day: ACE-I or ARBs 1
• Persistent proteinuria >1 g/day after ACE-I/ARB trial and GFR >50 ml/min/1.73m²: 6-month course of corticosteroids 1
• Crescentic HSP nephritis: Treat as for crescentic IgA nephropathy 1

For adults with IgA vasculitis:

• Treat the same as in children 1, 5
• For severe cases with significant organ involvement: corticosteroids combined with immunosuppressive drugs 5

Special Situations

IgA Nephropathy with Minimal Change Disease

• Treat as for minimal change disease with corticosteroids 1

IgA Nephropathy with AKI and Macroscopic Hematuria

• If kidney biopsy shows only acute tubular necrosis and intratubular erythrocyte casts: general supportive care 1
• If no improvement after 5 days: consider repeat kidney biopsy 1

IgA Nephropathy with eGFR <30 ml/min/1.73m²

• Generally treat with supportive care alone 1
• Exception: If active crescentic disease is present, immunosuppressive therapy is still indicated 1

Treatments to Avoid

• Antiplatelet agents are not recommended for IgA nephropathy 1, 4
• Tonsillectomy is not routinely recommended 1, 4
• Mycophenolate mofetil is not recommended for IgA nephropathy 1, 4
• Immunosuppressive therapy is not recommended for patients with GFR <30 ml/min/1.73m² unless crescentic disease is present 1, 4

Monitoring Response

• Regular assessment of proteinuria, hematuria, renal function, and blood pressure
• For crescentic disease, improvement in renal function should be seen within weeks to months of initiating therapy 3
• Consider follow-up kidney biopsy to assess healing of crescents in severe cases 3, 6

Prognosis

• Crescentic IgA nephropathy: With appropriate treatment, significant improvement in renal function can be achieved in many patients 3, 6
• Untreated crescentic IgA nephropathy has poor prognosis with rapid progression to end-stage renal disease 7
• Even with treatment, some patients with crescentic disease may progress to chronic kidney disease, but therapy appears to substantially delay the onset of dialysis 2

Treatment of IgA vasculitis and crescentic IgA glomerulonephritis requires aggressive immunosuppression to prevent irreversible kidney damage, while standard IgA nephropathy often responds to supportive care with selective use of corticosteroids in high-risk cases.