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

Initial Management of IgA Nephropathy

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

Risk Assessment and Initial Evaluation

• After biopsy-confirmed diagnosis, assess disease prognosis using the International IgAN Prediction Tool
• Document histologic scoring via the MEST-C system (mesangial and endocapillary hypercellularity, segmental glomerulosclerosis, interstitial fibrosis/tubular atrophy, and crescents)
• Identify patients at high risk of progression: those with proteinuria >0.75-1 g/day, hypertension, and/or reduced GFR at diagnosis

First-Line Management (Supportive Care)

1. RAS blockade:

   • Start ACE inhibitor or ARB for all patients with proteinuria >0.5 g/day (Grade 1B) 1, 2
   • Titrate to maximum tolerated dose to achieve proteinuria <1 g/day 1
   • Consider dual RAS blockade only in specific cases with careful monitoring 3

2. Blood pressure control:

   • Target BP <130/80 mmHg for patients with proteinuria <1 g/day
   • Target BP <125/75 mmHg for patients with proteinuria >1 g/day 1

3. Cardiovascular risk reduction:

   • Lifestyle modifications: dietary sodium restriction, smoking cessation, weight control, exercise 1
   • Address metabolic risk factors

Management of Persistent Proteinuria

For patients with persistent proteinuria >0.75-1 g/day despite 90 days of optimized supportive care:

1. Consider glucocorticoid therapy (6-month course) if:

   • eGFR ≥30 mL/min/1.73 m² (Grade 2B) 1
   • No contraindications (diabetes, obesity, latent infections, secondary disease, active peptic ulceration, uncontrolled psychiatric disease, severe osteoporosis)

2. Consider clinical trial enrollment when available 1, 2

3. Emerging therapies to consider (based on recent evidence):

   • SGLT2 inhibitors (shown to reduce CKD progression) 1, 2
   • Sparsentan (dual endothelin and angiotensin II receptor antagonist) 2, 4
   • Enteric-coated budesonide 2, 4
   • Complement inhibitors 2, 4

Special Situations

• IgA with minimal change disease: Treat according to MCD guidelines 1
• IgA with acute kidney injury from severe hematuria: Focus on supportive care for AKI; consider repeat biopsy if no improvement within 2 weeks 1
• IgA with rapidly progressive glomerulonephritis: Consider cyclophosphamide and corticosteroids if extensive crescent formation (>50% of glomeruli) 1, 5

Monitoring and Follow-up

• Regular monitoring of proteinuria, eGFR, and blood pressure
• Target proteinuria reduction to <1 g/day as a surrogate marker of improved kidney outcome 1, 6
• Recognize that even patients with proteinuria <0.88 g/g can have high rates of kidney failure within 10 years 6

Common Pitfalls to Avoid

1. Delaying RAS blockade: Even patients with normal blood pressure benefit from ACE inhibitors/ARBs if proteinuria >0.5 g/day 1

2. Underestimating risk in patients with "mild" proteinuria: Recent evidence shows that even patients with proteinuria <0.88 g/g have significant risk of kidney failure 6

3. Inappropriate use of immunosuppression: Avoid immunosuppressive agents other than glucocorticoids in standard IgA nephropathy, including azathioprine, cyclophosphamide, calcineurin inhibitors, and rituximab 1

4. Overlooking variant forms: IgA with minimal change disease, acute kidney injury, or rapidly progressive glomerulonephritis require specific management approaches 1