How is IgA (Immunoglobulin A) nephropathy diagnosed and treated?

Diagnosis and Treatment of IgA Nephropathy

Kidney biopsy with immunofluorescence showing mesangial dominant or co-dominant IgA deposits is the gold standard for diagnosing IgA nephropathy, followed by risk stratification and targeted treatment based on proteinuria levels and kidney function. 1

Diagnostic Process

Kidney Biopsy - Essential for Diagnosis

• Histopathological examination:
  • Light microscopy: Assess for mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescents (MEST-C score) 1
  • Immunofluorescence (IF): Critical for diagnosis - must show mesangial dominant or co-dominant IgA deposits 1
  • Electron microscopy (EM): Confirms location of deposits and evaluates glomerular basement membrane integrity 1

Immunofluorescence Findings (Diagnostic Hallmark)

• Pattern: Mesangial dominant or co-dominant IgA deposits 1
• Reporting standards:
  • Report whether staining is seen in some or all glomeruli
  • Note whether distribution is segmental or global
  • Specify location (mesangial, capillary wall, or both)
  • Describe staining type (granular, semilinear, etc.) 1

Risk Assessment After Diagnosis

• Apply MEST-C histologic scoring system 1
• Consider using International IgAN Prediction Tool (available at Calculate by QxMD) 1
• Identify high-risk features:
  • Proteinuria >1 g/day
  • Reduced eGFR at diagnosis
  • Hypertension
  • Advanced histologic findings 2, 3

Treatment Algorithm

1. Supportive Care (All Patients)

• First-line treatment for all patients regardless of risk:
  • Optimize blood pressure control (target <125/75 mmHg) 1, 2
  • Maximize RAS blockade with ACEi/ARB (indicated for proteinuria >0.5 g/day) 1
  • Lifestyle modifications (sodium restriction <2 g/day, weight control, smoking cessation) 1
  • Consider SGLT2 inhibitors for additional renoprotection 4

2. Risk-Stratified Treatment Approach

Low-Risk Patients

• Isolated microscopic hematuria or proteinuria <1 g/day:
  • Supportive care only
  • Regular monitoring of proteinuria and kidney function 2
  • Note: Even patients with proteinuria <0.88 g/g can have significant progression risk 3

Moderate to High-Risk Patients

• Persistent proteinuria >0.75-1 g/day despite 90 days of optimized supportive care:
  • Consider 6-month course of glucocorticoid therapy 1
  • Target: Reduce proteinuria to <1 g/day 1

Special Situations

• Nephrotic syndrome with minimal change on biopsy:

  • Treat as minimal change nephropathy 1, 2

• Rapidly progressive IgAN (crescentic, >50% of glomeruli):

  • Treat with cyclophosphamide and glucocorticoids (similar to ANCA-associated vasculitis) 1, 2

• Acute kidney injury from severe hematuria:

  • Supportive care for AKI
  • Consider repeat biopsy if no improvement within 2 weeks after hematuria resolves 1

Cautions and Contraindications

Glucocorticoid Therapy Cautions

• Use with extreme caution or avoid in patients with:
  • eGFR <30 ml/min/1.73 m²
  • Diabetes
  • Obesity (BMI >30 kg/m²)
  • Latent infections (TB, HIV, HBV, HCV)
  • Secondary disease (liver cirrhosis)
  • Active peptic ulceration
  • Uncontrolled psychiatric disease
  • Severe osteoporosis 1

Not Recommended Treatments

• Azathioprine
• Cyclophosphamide (except in rapidly progressive IgAN)
• Calcineurin inhibitors
• Rituximab 1

Monitoring and Follow-up

• Monitor proteinuria as surrogate marker of treatment response
• Track eGFR slope - aim for rate of decline ≤1 ml/min/1.73 m² per year 3
• Consider repeat biopsy in cases of unexpected disease course

Important Clinical Pitfalls

1. Misdiagnosis: Failure to perform immunofluorescence can lead to missed diagnosis
2. Underestimating risk: Even patients with "low-risk" proteinuria (<0.88 g/g) can progress to kidney failure within 10 years 3
3. Delayed treatment: Waiting too long to initiate immunosuppression in high-risk patients
4. Overtreatment: Using immunosuppression in patients with contraindications or low risk of progression
5. Inadequate supportive care: Failing to optimize blood pressure control and RAS blockade before considering immunosuppression

By following this diagnostic and treatment algorithm, clinicians can accurately diagnose IgA nephropathy and implement appropriate risk-stratified treatment to improve outcomes and reduce progression to end-stage kidney disease.