What is the primary approach to treating secondary IgA (Immunoglobulin A) nephropathy?

Treatment of Secondary IgA Nephropathy

The primary approach to treating secondary IgA nephropathy is to identify and treat the underlying disorder while providing optimized supportive care including renin-angiotensin system (RAS) blockade for patients with proteinuria >0.5 g/day. 1, 2

Diagnostic Approach

Before initiating treatment, it's essential to:

1. Identify the underlying cause of secondary IgA nephropathy, which may include:

   • Liver diseases (cirrhosis, alcoholic liver disease)
   • Inflammatory bowel diseases
   • Autoimmune conditions (lupus, rheumatoid arthritis)
   • Infections (HIV, hepatitis, syphilis)
   • Malignancies (particularly lymphoproliferative disorders)
   • Medications

2. Perform a comprehensive evaluation:

   • Kidney biopsy with MEST-C scoring (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents) 1
   • Assessment of proteinuria level, hematuria, and kidney function
   • Evaluation for secondary causes through appropriate serologic and imaging studies

Treatment Algorithm

Step 1: Treat the Underlying Disorder

• Liver disease: Optimize management of liver disease
• Inflammatory bowel disease: Treat with appropriate IBD therapies
• Autoimmune conditions: Manage the primary autoimmune disorder
• Infections: Provide appropriate antimicrobial therapy
• Malignancies: Treat the underlying malignancy
• Medication-induced: Discontinue offending medications

Step 2: Implement Supportive Care

• RAS blockade:

  • Initiate ACE inhibitor or ARB for patients with proteinuria >0.5 g/day (Grade 1B) 1, 2
  • Target blood pressure <130/80 mmHg for patients with proteinuria <1 g/day
  • Target blood pressure <125/75 mmHg for patients with proteinuria >1 g/day 2

• Lifestyle modifications:

  • Sodium restriction (<2.0 g/day)
  • Smoking cessation
  • Weight control and regular exercise
  • Dietary counseling 1, 2

• Consider SGLT2 inhibitors:

  • May be beneficial in reducing CKD progression, even in non-diabetic patients 1, 3

Step 3: Monitor Response

• Regular assessment of:
  • Proteinuria (target <1 g/day)
  • eGFR
  • Blood pressure
  • Activity of underlying disorder

Special Considerations

When to Consider Immunosuppression

Unlike primary IgA nephropathy, immunosuppression specifically for secondary IgA nephropathy is generally not recommended unless:

1. The underlying condition requires immunosuppression
2. There are features of rapidly progressive glomerulonephritis (crescents in >50% of glomeruli)
3. There is overlap with minimal change disease pattern 1, 2

High-Risk Features Requiring More Aggressive Management

• Proteinuria >1 g/day despite optimized supportive care
• Declining eGFR
• Extensive crescent formation
• Significant tubulointerstitial fibrosis

Important Caveats

• Avoid glucocorticoids in patients with:

  • eGFR <30 ml/min/1.73 m²
  • Diabetes
  • Obesity (BMI >30 kg/m²)
  • Latent infections
  • Active peptic ulceration
  • Uncontrolled psychiatric disease
  • Severe osteoporosis 1, 2

• Avoid dual RAS blockade (ACE inhibitor + ARB) due to increased risk of hyperkalemia without proven additional benefit 1

• Consider clinical trials for patients who remain at high risk of progression despite optimized supportive care 1

Emerging Therapies

Several promising therapies are under investigation that may benefit both primary and secondary IgA nephropathy:

• Targeted-release formulation of budesonide
• Sparsentan (dual endothelin and angiotensin receptor blocker)
• Complement inhibitors
• B-cell targeted therapies 3, 4, 5

By following this structured approach to treating secondary IgA nephropathy, clinicians can optimize outcomes by addressing both the underlying cause and the kidney manifestations of the disease.