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

Initial Management of IgA Nephropathy

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

Risk Assessment and Initial Evaluation

• Assess risk of progression using:

  • Proteinuria level
  • Blood pressure
  • eGFR at diagnosis
  • Pathological features (Oxford MEST-C score)
  • Consider using the International IgAN Prediction Tool 1, 2

• Evaluate for secondary causes of IgA nephropathy:

  • IgA vasculitis
  • Viral infections (HIV, hepatitis)
  • Inflammatory bowel disease
  • Autoimmune diseases
  • Liver cirrhosis 1

First-Line Management

1. Renin-Angiotensin System (RAS) Blockade:

   • Start ACEi or ARB for proteinuria >0.5 g/day (Grade 1B) 1, 2
   • Titrate dose upward to achieve proteinuria <1 g/day 2
   • Target BP <130/80 mmHg for patients with proteinuria <1 g/day
   • Target BP <125/75 mmHg for those with proteinuria >1 g/day 2
   • Dual RAS blockade (ACEi + ARB) is not recommended due to increased risk of hyperkalemia without proven additional benefit 1, 2

2. Lifestyle Modifications:

   • Dietary sodium restriction (<2.0 g/day) 1, 2
   • Smoking cessation
   • Weight control and exercise
   • Dietary protein modification based on proteinuria and kidney function:
     • For nephrotic-range proteinuria: 0.8-1 g/kg/day
     • For eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria: limit to 0.8 g/kg/day
     • Plant-based protein sources are preferred 1

3. SGLT2 Inhibitors:

   • Consider adding SGLT2 inhibitors to RAS blockade, particularly in patients with reduced eGFR
   • Evidence from DAPA-CKD and EMPA-KIDNEY trials shows significant benefit in non-diabetic kidney disease including IgAN 1, 2, 3

Management of Persistent Proteinuria Despite Supportive Care

For patients with persistent proteinuria >1 g/day despite optimized supportive care:

1. Corticosteroid Therapy:

   • Consider a 6-month course of corticosteroids for patients with eGFR ≥30 ml/min/1.73 m² (Grade 2B) 2
   • Contraindications include:
     • eGFR <30 ml/min/1.73 m²
     • Diabetes
     • Obesity (BMI >30 kg/m²)
     • Latent infections (TB, HIV, HBV, HCV)
     • Active peptic ulcer
     • Uncontrolled psychiatric disease
     • Severe osteoporosis 2

2. Other Options:

   • Fish oil may be considered (Grade 2D) 2
   • In Chinese patients, mycophenolate mofetil may be considered as a glucocorticoid-sparing agent 2
   • Newer therapies showing promise include sparsentan (dual endothelin-1 and angiotensin II receptor blocker), nefecon (targeted release formulation of budesonide), and iptacopan (complement factor B inhibitor) 3

Monitoring and Treatment Goals

• Regular monitoring of proteinuria, eGFR, and blood pressure
• Primary treatment goal: Reduce proteinuria to <1 g/day (surrogate marker of improved outcome) 2
• Assess cardiovascular risk and implement appropriate interventions 1, 2

Important Considerations and Pitfalls

• Avoid delaying treatment: Even patients with normal kidney function at diagnosis may progress to end-stage kidney disease over time 4
• Avoid overuse of immunosuppression: The benefits of immunosuppression must be weighed against potential serious adverse effects, particularly infections 3, 5
• Don't overlook variant forms of IgAN: IgA deposition with minimal change disease, IgAN with acute kidney injury, and IgAN with rapidly progressive glomerulonephritis require specific immediate treatment 1, 2
• Be cautious with tonsillectomy: Evidence is limited mainly to Japanese populations and is of low certainty 6
• Consider clinical trials: Patients should be offered participation in disease registries and clinical trials when available 1

The management of IgA nephropathy has evolved significantly, with a strong focus on optimized supportive care as the foundation of treatment, supplemented by targeted therapies for patients with persistent proteinuria or high risk of progression.