What is the treatment for Berger's disease (IgA nephropathy)?

Treatment for Berger's Disease (IgA Nephropathy)

The primary treatment for IgA nephropathy should focus on optimized supportive care with RAS blockade (ACEi or ARB) as first-line therapy for patients with proteinuria >0.5 g/day, with addition of SGLT2 inhibitors when eGFR ≥20 ml/min/1.73m², and consideration of glucocorticoid therapy only for high-risk patients with persistent proteinuria >0.75-1 g/day despite maximal supportive care. 1, 2

Treatment Algorithm

First-Line Treatment: Optimized Supportive Care

• Blood pressure management: Target <130/80 mmHg for patients with proteinuria <1 g/day and <125/75 mmHg for those with proteinuria ≥1 g/day 2
• RAS blockade:
  • Start ACEi (e.g., ramipril) or ARB (e.g., losartan) at maximum tolerated dose for all patients with proteinuria >0.5 g/day 1
  • Monitor renal function and potassium 2-4 weeks after initiation or dose adjustment 2
  • Suspend during episodes of dehydration 2
• Add SGLT2 inhibitors (dapagliflozin or empagliflozin) when eGFR ≥20 ml/min/1.73m² 1, 2
  • DAPA-CKD and EMPA-KIDNEY trials showed significant benefits in non-diabetic kidney disease including IgA nephropathy 1
• Lifestyle modifications:
  • Dietary sodium restriction
  • Smoking cessation
  • Weight control
  • Regular exercise 1

Second-Line Treatment for High-Risk Patients

High-risk defined as proteinuria >0.75-1 g/day despite ≥90 days of optimized supportive care 1

For patients with eGFR ≥30 ml/min/1.73m²:

• Consider a 6-month course of glucocorticoid therapy 1
  • The TESTING study showed benefit but with increased risk of adverse events 1
  • Include prophylaxis against Pneumocystis pneumonia, gastroprotection, and bone protection 1
  • OR
• Consider targeted-release budesonide (FDA-approved for primary IgA nephropathy with UPCR >1.5 g/g) 1

Additional options for specific populations:

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

Contraindications/Cautions for Glucocorticoid Therapy

Avoid or use extreme caution with glucocorticoids in patients with:

• eGFR <30 ml/min/1.73m²
• Diabetes
• Obesity (BMI >30 kg/m²)
• Latent infections (viral hepatitis, tuberculosis)
• Secondary disease (liver cirrhosis)
• Active peptic ulceration
• Uncontrolled psychiatric disease
• Severe osteoporosis 1

Additional Treatments for Resistant Hypertension

• Add thiazide or thiazide-like diuretics (consider loop diuretics if eGFR <30 ml/min/1.73m²)
• Add calcium channel blockers if hypertension persists 2

Monitoring and Follow-up

• Monitor renal function and electrolytes 2-4 weeks after initiating or adjusting treatment 2
• Monitor proteinuria every 3 months to evaluate response 2
• Target: Reduce proteinuria to <1 g/day (surrogate marker of improved kidney outcome) 1
• Suspend ACEi/ARB if creatinine increases >30% or refractory hyperkalemia develops 2

Special Considerations

• Variant forms of IgA nephropathy (IgA deposition with minimal change disease, IgA with acute kidney injury, IgA with rapidly progressive glomerulonephritis) may require specific immediate treatment 1
• Not recommended: Azathioprine, cyclophosphamide (except in rapidly progressive IgAN), calcineurin inhibitors, rituximab 1
• Fish oil may be considered for patients with progressive disease (creatinine clearance <70 ml/min) 3, though evidence is mixed 4

Common Pitfalls

• Delaying initiation of RAS blockade in patients with proteinuria >0.5 g/day
• Using dual RAS blockade (ACEi + ARB), which shows no additional benefit and increases risk of hyperkalemia 1
• Failing to add SGLT2 inhibitors, which provide significant kidney and cardiovascular protection 1, 2
• Initiating glucocorticoids without adequate trial of optimized supportive care
• Not providing prophylaxis against Pneumocystis pneumonia when using glucocorticoids 1
• Overlooking the need to suspend ACEi/ARB during episodes of dehydration 2

By following this treatment algorithm, the goal is to reduce proteinuria to <1 g/day, which is associated with improved kidney outcomes and reduced progression to end-stage kidney disease in patients with IgA nephropathy.