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

Initial Treatment Approach for IgA Nephropathy

The primary focus of management for IgA nephropathy should be optimized supportive care, with renin-angiotensin system (RAS) blockade using ACE inhibitors or ARBs as first-line therapy for all patients with proteinuria >0.5 g/day, regardless of blood pressure status. 1

Risk Assessment

Before initiating treatment, assess the risk of progression by evaluating:

• Proteinuria level (key prognostic factor)
• Blood pressure
• eGFR at diagnosis
• Pathological features using MEST-C scoring system

The International IgAN Prediction Tool (available at Calculate by QxMD) can help assess prognosis, though it cannot determine treatment response 1.

Initial Treatment Algorithm

Step 1: Supportive Care for All Patients

• Blood pressure control:

  • Target <130/80 mmHg if proteinuria <1 g/day
  • Target <125/75 mmHg if proteinuria ≥1 g/day 1

• RAS blockade:

  • ACE inhibitor or ARB for all patients with proteinuria >0.5 g/day (Grade 1B) 1
  • Titrate to maximum tolerated dose to achieve proteinuria <1 g/day 1
  • Consider adding SGLT2 inhibitors (emerging evidence shows benefit) 1

• Lifestyle modifications:

  • Dietary sodium restriction (<2.0 g/day)
  • Smoking cessation
  • Weight control
  • Regular exercise 1

Step 2: Monitor Response to Supportive Care (3-6 months)

• Regularly assess proteinuria, blood pressure, and kidney function
• Target: Reduction of proteinuria to <1 g/day (associated with favorable outcomes) 1

Step 3: Management of Persistent Proteinuria

If proteinuria remains >0.75-1 g/day despite 3-6 months of optimized supportive care:

• For patients with eGFR ≥50 ml/min/1.73m²: Consider a 6-month course of corticosteroid therapy (Grade 2B) 1

• Corticosteroid regimen:

  • Methylprednisolone 1g IV for 3 days at months 1,3, and 5, plus
  • Oral prednisone 0.8-1 mg/kg/day for 2 months, then taper by 0.2 mg/kg/day monthly over 4 months 2

Special Situations

Variant Forms of IgAN

• IgA with minimal change disease: Treat as minimal change disease 1
• Crescentic IgAN (>50% crescents with rapidly progressive deterioration): Use steroids plus cyclophosphamide, similar to ANCA vasculitis treatment 1

Contraindications/Cautions for Corticosteroids

Avoid or use extreme caution with corticosteroids in patients with:

• eGFR <30 ml/min/1.73m²
• Diabetes
• Obesity (BMI >30 kg/m²)
• Latent infections
• Active peptic ulceration
• Uncontrolled psychiatric disease
• Severe osteoporosis 1

Other Immunosuppressive Agents

Not recommended in standard IgA nephropathy:

• Cyclophosphamide or azathioprine (except in crescentic IgAN)
• Calcineurin inhibitors
• Rituximab
• Mycophenolate mofetil (except possibly in Chinese patients) 1

Common Pitfalls to Avoid

1. Delaying RAS blockade: Start ACE inhibitors or ARBs promptly in patients with proteinuria >0.5 g/day, even with normal blood pressure

2. Inadequate dose titration: Maximize RAS blockade to the highest tolerated dose to achieve proteinuria <1 g/day

3. Premature immunosuppression: Use corticosteroids only after adequate trial of optimized supportive care (3-6 months)

4. Overlooking variant forms: Recognize and appropriately treat special situations like crescentic IgAN or IgA with minimal change disease

5. Ignoring comorbidities: Address cardiovascular risk factors comprehensively

6. Insufficient monitoring: Regular follow-up of proteinuria, blood pressure, and kidney function is essential to assess response and adjust therapy

The evidence strongly supports that optimized supportive care with RAS blockade should be the cornerstone of initial management for all IgA nephropathy patients with proteinuria >0.5 g/day, with corticosteroids reserved for those with persistent significant proteinuria despite optimal supportive care.