What is the initial treatment for IgA Nephropathy (IgAN)?

Initial Treatment for IgA Nephropathy

All patients with IgA nephropathy should begin with optimized supportive care consisting of ACE inhibitor or ARB therapy combined with strict blood pressure control for at least 3-6 months before considering any immunosuppressive therapy. 1, 2

Step 1: Risk Stratification at Diagnosis

Immediately assess three key prognostic factors at diagnosis and throughout follow-up 1, 2:

• Proteinuria level (most critical determinant of treatment pathway) 1, 2
• Blood pressure 1
• eGFR (estimated glomerular filtration rate) 1, 2
• Pathological features using Oxford MEST score may provide additional prognostic information, though its incremental value beyond clinical markers remains uncertain 1

Step 2: Initiate Supportive Care (First-Line for ALL Patients)

ACE Inhibitor or ARB Therapy

For proteinuria ≥1 g/day: Long-term ACE inhibitor or ARB treatment is strongly recommended (1B evidence) 1, 2

For proteinuria 0.5-1 g/day: ACE inhibitor or ARB treatment is suggested (2D evidence) 1, 2

Dosing strategy: Titrate upward to the maximum tolerated dose to achieve proteinuria <1 g/day, adjusting based on blood pressure tolerance 1, 2

Blood Pressure Targets (Proteinuria-Dependent)

The blood pressure goal is stratified by proteinuria level 1, 2:

• If proteinuria <1 g/day: Target BP <130/80 mmHg 1, 2
• If proteinuria ≥1 g/day: Target BP <125/75 mmHg 1, 2

Critical caveat: These blood pressure targets are opinion-based rather than derived from randomized controlled trials comparing different BP goals, though meta-analyses suggest trends toward improved outcomes with more aggressive control in proteinuric patients 1

Duration of Supportive Care Trial

Continue optimized supportive care (maximized ACE-I/ARB plus BP control) for 3-6 months before reassessing for potential immunosuppression 1, 2

Step 3: Reassess After Supportive Care Trial

If Proteinuria Reduces to <1 g/day

Continue supportive care only - reduction of proteinuria to <1 g/day is associated with favorable long-term outcomes regardless of whether achieved through conservative or immunomodulatory approaches 1, 2

If Proteinuria Remains ≥1 g/day Despite Optimized Supportive Care

Consider adding corticosteroids if the following criteria are ALL met 1, 2:

• Persistent proteinuria ≥1 g/day after 3-6 months of optimized supportive care
• eGFR >50 mL/min/1.73 m² (corticosteroids carry increased adverse events as GFR declines)
• No contraindications to corticosteroid therapy

Corticosteroid regimen (6-month course) 1, 2:

• IV methylprednisolone 1 gram for 3 consecutive days at months 1,3, and 5
• PLUS oral prednisone 0.5 mg/kg on alternate days for 6 months

Evidence supporting corticosteroids: An Italian trial demonstrated 10-year renal survival of 97% with corticosteroids versus 53% without immunosuppression, though this comes with significant side effect risks 1, 2

Step 4: Additional Supportive Therapies

Fish Oil

Consider fish oil supplementation for patients with persistent proteinuria >1 g/day despite 3-6 months of optimized supportive care (2D evidence) 1, 2

Special Clinical Scenarios Requiring Different Approaches

Crescentic IgA Nephropathy (Rapidly Progressive)

Definition: >50% of glomeruli with crescents on biopsy AND rapidly progressive renal deterioration 1, 2

Treatment: Steroids PLUS cyclophosphamide (analogous to ANCA vasculitis treatment), regardless of baseline eGFR 1, 2

Minimal Change Disease Pattern with IgA Deposits

Treatment: Manage as minimal change disease (not as typical IgAN) in nephrotic patients showing MCD pathology with mesangial IgA deposits 1, 2

What NOT to Do: Avoiding Common Pitfalls

Do NOT use these therapies 1, 2:

• Mycophenolate mofetil (MMF) - not recommended in IgAN (2C evidence) 1, 2
• Corticosteroids combined with cyclophosphamide or azathioprine - except in crescentic IgAN 1
• Any immunosuppression in patients with eGFR <30 mL/min/1.73 m² - unless crescentic disease with rapid deterioration 2
• Antiplatelet agents or anticoagulants - no evidence supports their use specifically for IgAN 2
• Tonsillectomy - evidence does not support this approach 2

Critical warning: Many older trials used suboptimal blood pressure goals of 140/90 mmHg, which are now considered inadequate for optimal renoprotection in IgAN 1, 2

Monitoring Strategy

The therapeutic goal is reduction of proteinuria to <1 g/day, which correlates with favorable outcomes regardless of how this reduction is achieved 1, 2. Continuously monitor proteinuria, blood pressure, and eGFR during follow-up to guide treatment adjustments 1, 2.