What is the treatment for IgA (Immunoglobulin A) nephropathy?

Treatment of IgA Nephropathy

The treatment of IgA nephropathy should begin with optimized supportive care, including ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, with additional therapies based on risk stratification and response to initial treatment. 1

Initial Risk Assessment and Supportive Care

Risk Assessment

• Evaluate proteinuria, blood pressure, and eGFR at diagnosis and during follow-up 1
• Consider pathological features (Oxford MEST score) for prognostic information 1
• Reduction of proteinuria to <1 g/day is a key surrogate marker of improved kidney outcomes 1

First-Line Therapy (All Patients)

• Blood pressure control:
  • Target <130/80 mmHg if proteinuria <1 g/day
  • Target <125/75 mmHg if proteinuria ≥1 g/day 1, 2
• Renin-angiotensin system blockade:
  • ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day 1, 2
  • Titrate to maximum tolerated dose to achieve proteinuria <1 g/day 1
  • Consider combination therapy with both ACE inhibitor and ARB for resistant cases 3, 4
• Lifestyle modifications:
  • Sodium restriction (<2 g/day) to enhance antiproteinuric effects 2
  • Weight management if overweight/obese

Treatment Algorithm Based on Response to Supportive Care

For Patients with Persistent Proteinuria ≥1 g/day Despite 3-6 Months of Optimized Supportive Care:

If eGFR ≥50 ml/min/1.73 m²:

• Consider 6-month course of corticosteroid therapy 1
  • Therapeutic regimen: methylprednisolone 1 g IV for 3 days at months 1,3, and 5, plus oral prednisone 0.8-1 mg/kg/day for 2 months, then taper over 4 months 2
  • Caution: Carefully assess risk/benefit profile before initiating steroids, especially in patients with:
    • Advanced age
    • Metabolic syndrome
    • Obesity
    • Latent infections (TB, HIV, HBV, HCV)
    • Diabetes
    • Severe osteoporosis
    • Psychiatric disease
    • Peptic ulceration 1

If eGFR 30-50 ml/min/1.73 m²:

• Continue optimized supportive care
• Consider clinical trial enrollment
• Consider fish oil supplementation for persistent proteinuria >1 g/day 1

If eGFR <30 ml/min/1.73 m²:

• Avoid immunosuppressive therapy 1
• Focus on optimized supportive care
• Consider SGLT2 inhibitors based on emerging evidence 1, 5, 6

Special Populations:

• Chinese patients: Consider mycophenolate mofetil as a glucocorticoid-sparing agent 1
• Japanese patients: Consider tonsillectomy 1

Management of Variant Forms of IgAN

IgAN with Minimal Change Disease Features:

• Treat as minimal change disease with standard steroid regimen 1

Crescentic IgAN (>50% crescents with rapidly progressive deterioration):

• Treat with steroids and cyclophosphamide, similar to ANCA vasculitis 1

IgAN with AKI from Macroscopic Hematuria:

• Provide supportive care for AKI
• Consider kidney biopsy if no improvement after 2 weeks 1

Emerging Therapies

Several new therapies are being evaluated for high-risk IgAN patients:

• SGLT2 inhibitors
• Sparsentan (dual endothelin-1 and angiotensin II receptor blocker)
• Enteric-coated budesonide (targeted-release formulation)
• Complement inhibitors (e.g., iptacopan)
• Therapies targeting B-cell development 1, 5, 6

Monitoring and Follow-up

• Regular monitoring of proteinuria, eGFR, blood pressure, and hematuria 2
• Adjust therapy based on response, particularly focusing on proteinuria reduction
• Target proteinuria reduction to <1 g/day as a surrogate marker for improved outcomes 1

Pitfalls and Caveats

• Do not use corticosteroids combined with cyclophosphamide or azathioprine except in crescentic IgAN 1
• Do not use mycophenolate mofetil in non-Chinese patients 1
• Do not use immunosuppression in patients with eGFR <30 ml/min/1.73 m² unless there is crescentic IgAN 1
• Tonsillectomy is not recommended for non-Japanese patients 1
• Antiplatelet agents are not recommended for treating IgAN 1
• Adverse treatment effects are more likely in patients with eGFR <50 ml/min/1.73 m² 1