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

Initial Management of IgA Nephropathy

The primary focus of management for IgA nephropathy should be optimized supportive care, with ACE inhibitors or ARBs as first-line therapy for all patients with proteinuria >0.5 g/day, regardless of blood pressure status. 1, 2

Risk Assessment

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

• Proteinuria level
• Blood pressure
• eGFR at diagnosis
• Pathological features using MEST-C scoring system

The International IgAN Prediction Tool can help assess prognosis, though it cannot determine treatment response 1.

Step-by-Step Management Algorithm

Step 1: Blood Pressure Control and RAS Blockade

• Target blood pressure:
  • <130/80 mmHg if proteinuria <1 g/day
  • <125/75 mmHg if proteinuria ≥1 g/day 2, 1
• Medication:
  • Start ACE inhibitor or ARB for all patients with proteinuria >0.5 g/day 2, 1
  • Titrate to maximum tolerated dose to achieve proteinuria <1 g/day 1
  • Consider adding SGLT2 inhibitors as emerging evidence shows benefit 2, 3

Step 2: Lifestyle Modifications

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

Step 3: Monitoring Response

• Regularly assess proteinuria, blood pressure, and kidney function
• Target reduction of proteinuria to <1 g/day (associated with favorable outcomes) 1
• Allow 3-6 months of optimized supportive care before considering additional therapies 2

Step 4: For Persistent Proteinuria Despite Supportive Care

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 2, 1

• 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 2

Special Situations

Variant Forms of IgA Nephropathy

1. IgA with minimal change disease:

   • Treat as minimal change disease 2, 1

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

   • Treat with steroids plus cyclophosphamide, similar to ANCA vasculitis treatment 2, 1

3. IgAN with acute kidney injury from severe hematuria:

   • Focus on supportive care for AKI
   • Consider repeat kidney biopsy if no improvement within 2 weeks after hematuria resolves 2

Treatments Not Recommended for Standard IgA Nephropathy

• Cyclophosphamide or azathioprine (except in crescentic IgAN)
• Calcineurin inhibitors
• Rituximab
• Mycophenolate mofetil (except possibly in Chinese patients) 2, 1

Important Caveats

1. Early IgA nephropathy with minimal proteinuria: Treatment with ACE inhibitors may not offer benefit for patients with proteinuria <0.5 g/day, normal blood pressure, and normal renal function 4.

2. Dual ACE inhibitor-ARB therapy: While some older studies suggested benefits 5, more recent guidelines do not recommend this approach due to safety concerns and lack of additional benefit in subgroup analyses 2.

3. Monitoring for adverse effects of medications:

   • With ACE inhibitors/ARBs: Monitor for hyperkalemia, acute kidney injury, and hypotension
   • With corticosteroids: Monitor for infections, hyperglycemia, weight gain, and mood changes

4. Emerging therapies: New treatments including SGLT2 inhibitors, sparsentan, targeted-release budesonide, and complement inhibitors are showing promise in recent trials and may change the treatment paradigm in coming years 3.