What is the treatment for IgA (Immunoglobulin A) nephropathy?

IgA Nephropathy and Its Treatment

The primary treatment for IgA nephropathy (IgAN) should be optimized supportive care, including RAS blockade, blood pressure control, and cardiovascular risk reduction, with glucocorticoids considered only in specific high-risk patients with persistent proteinuria despite supportive measures. 1

What is IgA Nephropathy?

IgA nephropathy is the most common primary glomerular disease worldwide, characterized by:

• Mesangial deposition of immunoglobulin A in the glomeruli 2, 3
• Clinical presentation ranging from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis 4, 5
• Variable disease course with 25-30% of patients developing end-stage kidney disease within 20 years 4
• Pathogenesis involving dysregulation of the immune system with abnormal synthesis of deglycosylated IgA1 3, 5

Diagnosis and Prognosis Assessment

• Diagnosis requires kidney biopsy with histologic scoring via the MEST-C system (Mesangial hypercellularity, Endocapillary hypercellularity, Segmental glomerulosclerosis, Tubular atrophy/interstitial fibrosis, and Crescents) 1
• Prognosis can be assessed using the International IgAN Prediction Tool (available at Calculate by QxMD) 1
• Risk factors for progression include hypertension, proteinuria >1 g/day, and reduced GFR at diagnosis 4, 6

Treatment Approach

First-Line: Optimized Supportive Care

All patients should receive optimized supportive care, which includes: 1

• RAS blockade (ACEi/ARB) for all patients with proteinuria >0.5 g/day, regardless of hypertension status (Grade 1B) 1
• Blood pressure control to target 125/75 mmHg in patients with proteinuria >1 g/day 1
• Cardiovascular risk reduction measures 1
• Lifestyle modifications:
  • Dietary counseling and salt restriction 2
  • Smoking cessation 6
  • Weight control 1
  • Regular exercise 6

Second-Line: Glucocorticoid Therapy

Consider a 6-month course of glucocorticoids (Grade 2B) if: 1

• Proteinuria remains >0.75-1 g/day despite at least 90 days of optimized supportive care 1
• eGFR is ≥30 ml/min/1.73 m² 1
• Patient has no contraindications to glucocorticoid therapy 1

Contraindications to glucocorticoid therapy include: 1

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

Special Populations and Considerations

• Chinese patients: May consider mycophenolate mofetil (MMF) as a glucocorticoid-sparing agent 1
• Japanese patients: May consider tonsillectomy 1
• Rapidly progressive IgAN: Treatment with cyclophosphamide and glucocorticoids is recommended for patients with extensive crescent formation (>50% of glomeruli) and declining GFR 1
• IgAN with minimal change disease: Treat according to minimal change disease guidelines 1
• IgAN with acute kidney injury from severe hematuria: Focus on supportive care for AKI 1

Therapies Not Recommended for General Use

The following therapies are not recommended for routine use in IgAN: 1

• Azathioprine 1
• Cyclophosphamide (except in rapidly progressive IgAN) 1
• Calcineurin inhibitors 1
• Rituximab 1
• Mycophenolate mofetil (except in Chinese patients) 1
• Tonsillectomy (except in Japanese patients) 1

Emerging Therapies

Several new therapies are currently being evaluated: 1

• SGLT2 inhibitors 1
• Sparsentan and atrasentan 1
• Hydroxychloroquine 1
• Enteric-coated budesonide (recently received FDA accelerated approval for primary IgA nephropathy with UPCR >1.5 g/g) 1
• Complement inhibitors 1, 2
• Therapies targeting B-cell development 1, 2

Treatment Goals and Monitoring

• Aim to reduce proteinuria to <1 g/day as a surrogate marker of improved kidney outcome 1
• Monitor proteinuria, blood pressure, and eGFR regularly to assess response to therapy 1
• Consider clinical trial enrollment for patients with persistent proteinuria >1 g/day despite optimized supportive care 1