What are the initial management and treatment guidelines for patients with Immunoglobulin A (IGA) nephropathy according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines?

KDIGO Guidelines for Initial Management and Treatment of IgA Nephropathy

The initial management of IgA nephropathy should focus on optimized supportive care for at least 90 days, including maximizing RAS blockade with ACEi or ARB, strict BP control, and lifestyle modifications, before considering immunosuppressive therapy. 1, 2

Initial Assessment and Risk Stratification

1. Assessment for secondary causes 1:

   • Rule out IgA vasculitis
   • Secondary IgAN (viral infections, inflammatory bowel disease, autoimmune disease, liver cirrhosis)
   • IgA-dominant infection-related glomerulonephritis

2. Risk stratification 1:

   • Proteinuria level (>1 g/day indicates high risk)
   • Blood pressure
   • eGFR at diagnosis
   • Pathological features (MEST-C score)

First-Line Treatment: Optimized Supportive Care

Blood Pressure and Proteinuria Management

• ACEi or ARB therapy 1, 2:

  • Mandatory for proteinuria >1 g/day (Grade 1B)
  • Recommended for proteinuria 0.5-1 g/day (Grade 2D)
  • Titrate to maximum tolerated dose to achieve proteinuria <1 g/day

• Blood pressure targets 1, 3:

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

Lifestyle Modifications 1, 2

• Dietary sodium restriction (<2.0 g/day)
• Smoking cessation
• Weight control (target BMI <30 kg/m²)
• Regular exercise
• Protein restriction:
  • 0.8-1 g/kg/day for nephrotic-range proteinuria
  • 0.8 g/kg/day for eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria

Second-Line Treatment: Immunosuppressive Therapy

Glucocorticoid Therapy Consideration 1, 2

Consider glucocorticoids only if:

• Persistent proteinuria >1 g/day despite 3 months of optimized supportive care
• eGFR ≥30 ml/min/1.73 m²

Contraindications for glucocorticoid therapy 1:

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

Other Immunosuppressive Therapies 1

The following are not recommended for standard IgAN:

• Azathioprine
• Cyclophosphamide (except in rapidly progressive IgAN)
• Calcineurin inhibitors
• Rituximab

Special population considerations:

• Mycophenolate mofetil may be considered as a glucocorticoid-sparing agent in Chinese patients
• Tonsillectomy may be considered in Japanese patients

Special Situations in IgAN

1. IgAN with minimal change disease 1:

   • Treat according to minimal change disease guidelines

2. IgAN with acute kidney injury from severe hematuria 1:

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

3. IgAN with rapidly progressive glomerulonephritis 1:

   • Consider cyclophosphamide and corticosteroids if extensive crescent formation (>50% of glomeruli)

Emerging Therapies

Several new therapies are being evaluated 1, 4:

• SGLT2 inhibitors
• Sparsentan (dual endothelin-1 and angiotensin II receptor blocker)
• Enteric-coated budesonide
• Complement inhibitors
• Therapies targeting B-cell development

Monitoring and Follow-up

• Regular monitoring of proteinuria, eGFR, and blood pressure
• Proteinuria reduction to <1 g/day is a surrogate marker of improved kidney outcome 1, 5
• Early response to therapy (proteinuria reduction at 6 months) predicts better long-term outcomes 5

Common Pitfalls to Avoid

1. Delaying RAS blockade in patients with normal blood pressure but proteinuria >0.5 g/day 2
2. Premature initiation of immunosuppression before optimizing supportive care for at least 3 months 1
3. Using immunosuppression in patients with contraindications, particularly eGFR <30 ml/min/1.73 m² 1
4. Inadequate blood pressure control - failure to achieve target BP is associated with faster eGFR decline 3, 5
5. Overlooking special variants of IgAN that require specific treatment approaches 1