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

Initial Treatment Approach for IgA Nephropathy

The cornerstone of initial treatment for IgA nephropathy is optimized supportive care with ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, combined with strict blood pressure control, before considering any immunosuppressive therapy. 1, 2

Step 1: Risk Assessment and Baseline Evaluation

Begin by assessing risk of progression through evaluation of:

• Proteinuria level (the most critical prognostic factor) 1
• Blood pressure at diagnosis and during follow-up 1
• eGFR to establish baseline kidney function 1
• Pathological features using the Oxford MEST-C scoring system for additional prognostic information 1, 2

The threshold of proteinuria >1 g/day is associated with worse kidney outcomes and guides treatment intensity 1.

Step 2: Initiate Optimized Supportive Care (First-Line for ALL Patients)

Blood Pressure and RAS Blockade

• Start ACE inhibitor or ARB therapy for proteinuria >0.5 g/day, regardless of whether hypertension is present (Grade 1B) 1, 2
• Titrate ACE inhibitor or ARB upward as tolerated to achieve proteinuria <1 g/day 1
• Blood pressure targets:
  • <130/80 mmHg for proteinuria <1 g/day 1
  • <125/75 mmHg for proteinuria >1 g/day 1

Important caveat: Do NOT use dual ACE inhibitor plus ARB therapy—this combination provides no additional benefit and increases risk of hyperkalemia 1.

Lifestyle and Cardiovascular Risk Modification

• Dietary sodium restriction (the only dietary intervention with proven benefit) 1, 2
• Smoking cessation 3
• Weight control and exercise program 2, 3
• Cardiovascular risk assessment and management 1, 2

Emerging Supportive Therapy

• Consider adding SGLT2 inhibitor (e.g., dapagliflozin or empagliflozin) to ACE inhibitor/ARB therapy, based on recent evidence from DAPA-CKD and EMPA-KIDNEY trials showing significant kidney benefit in non-diabetic glomerulonephritis 1

Step 3: Reassess After 3-6 Months of Optimized Supportive Care

Monitor proteinuria, blood pressure, and eGFR regularly to determine response to supportive therapy 1.

If Proteinuria Remains ≥0.75-1 g/day Despite 90 Days of Maximal Supportive Care:

Consider adding a 6-month course of corticosteroids ONLY if:

• Proteinuria persists ≥1 g/day after 3-6 months of optimized supportive care 1
• eGFR >50 ml/min/1.73 m² (some guidelines use ≥30 ml/min/1.73 m²) 1
• No contraindications to corticosteroid therapy exist 1

Corticosteroid regimen options (Grade 2C):

• IV methylprednisolone 1 g for 3 days at months 1,3, and 5, PLUS oral prednisone 0.5 mg/kg every other day for 6 months 1
• OR oral prednisone starting at 0.8-1 mg/kg/day for 2 months, then taper by 0.2 mg/kg/day per month over 4 months 1

Critical warning: The benefit-to-risk ratio of corticosteroids is controversial, and adverse events increase markedly as eGFR declines 4. Given current uncertainty, offer enrollment in clinical trials when available 1.

Step 4: Special Situations Requiring Different Approaches

Crescentic IgA Nephropathy (Rapidly Progressive)

• Defined as: >50% of glomeruli with crescents and rapidly declining kidney function 1
• Treatment: Cyclophosphamide plus corticosteroids, similar to ANCA vasculitis regimen 1

IgA Nephropathy with Minimal Change Disease Pattern

• Treatment: Manage as minimal change disease with corticosteroids 1

Geographic Considerations

• Chinese patients: May consider mycophenolate mofetil as glucocorticoid-sparing agent 2, 4
• Japanese patients: May consider tonsillectomy 2

Therapies NOT Recommended for Routine Use

Avoid the following unless in specific circumstances:

• Mycophenolate mofetil (except in Chinese patients) 1, 2
• Cyclophosphamide or azathioprine combined with corticosteroids (except crescentic IgAN) 1
• Cyclosporine (limited evidence) 1
• Fish oil (weak evidence, Grade 2D) 1

Common Pitfalls to Avoid

• Starting immunosuppression before adequate trial of supportive care: Always give 3-6 months of optimized ACE inhibitor/ARB therapy and blood pressure control first 1
• Using corticosteroids in patients with eGFR <30-50 ml/min/1.73 m²: Risk of adverse events outweighs potential benefit 1
• Dual ACE inhibitor plus ARB therapy: No additional benefit and increased harm 1
• Abrupt discontinuation of calcineurin inhibitors if used: Taper slowly while monitoring proteinuria 1
• Ignoring cardiovascular risk: IgA nephropathy patients have significant cardiovascular morbidity requiring attention 1, 2

Treatment Goal

Aim to reduce proteinuria to <1 g/day, which is associated with favorable long-term kidney outcomes regardless of whether achieved through supportive care alone or with immunosuppression 1, 2.