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

Initial Treatment for IgA Nephropathy

The cornerstone of initial treatment for IgA nephropathy is optimized supportive care with ACE inhibitors or ARBs for patients with proteinuria >0.5 g/day, combined with blood pressure control and lifestyle modifications. 1

Risk Stratification First

Before initiating treatment, assess progression risk by measuring:

• Proteinuria levels (24-hour urine or protein-to-creatinine ratio) 1
• Blood pressure 1
• eGFR at diagnosis 1
• Pathological features (Oxford MEST score if available) 1

Patients with proteinuria >0.75-1 g/day, hypertension, or reduced eGFR at diagnosis are at highest risk for progression. 1, 2

First-Line: Optimized Supportive Care

Blood Pressure Management

All patients require blood pressure optimization, with specific targets based on proteinuria levels: 1

• Proteinuria <1 g/day: Target BP <130/80 mmHg 1
• Proteinuria ≥1 g/day: Target BP <125/75 mmHg 1

ACE Inhibitor or ARB Therapy

For proteinuria >0.5 g/day, initiate either an ACE inhibitor OR an ARB (not both) as first-line therapy: 1

• This represents an evolution from older guidelines that used a 1 g/day threshold; the 2021 KDIGO guideline lowered this to 0.5 g/day 1
• Titrate upward to maximally tolerated doses to achieve proteinuria <1 g/day 1, 3
• Do not use dual ACE inhibitor and ARB therapy - the STOP-IgAN trial showed no additional benefit and increased hyperkalemia risk 1
• Accept up to 30% increase in serum creatinine after initiation; this is expected and should not prompt discontinuation 1

For proteinuria <0.5 g/day with normal blood pressure: The benefit of ACE inhibitor/ARB therapy is unclear in this population, as there is insufficient data. 1 Consider watchful waiting with close monitoring. 4

Lifestyle Modifications

Implement the following non-pharmacologic interventions for all patients: 1

• Dietary sodium restriction to <2.0 g/day (<90 mmol/day) 1
• Smoking cessation 1
• Weight control and regular exercise 1
• Cardiovascular risk assessment and management 1

No other specific dietary interventions (beyond sodium restriction) have been shown to alter outcomes in IgA nephropathy. 1

SGLT2 Inhibitors - Emerging Role

Consider adding an SGLT2 inhibitor (dapagliflozin or empagliflozin) to ACE inhibitor/ARB therapy: 1

• The DAPA-CKD trial included patients with glomerulonephritis and showed a 36% reduction (HR 0.64) in the composite outcome of 50% eGFR reduction or kidney failure 1
• The EMPA-KIDNEY trial included >800 patients with IgA nephropathy and showed similar benefits 1
• While no IgA nephropathy-specific RCTs exist, the evidence from these trials is compelling enough that KDIGO commentary highlights their "positive long-term potential for kidney outcomes" 1

Duration of Supportive Care Before Escalation

Provide 3-6 months (≥90 days) of optimized supportive care before considering immunosuppression. 1, 3 This allows time to assess response to renin-angiotensin system blockade and blood pressure control.

When to Consider Immunosuppression

Reserve corticosteroids for high-risk patients with: 1, 3

• Persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care
• GFR >50 mL/min/1.73 m² 1, 3

The typical regimen includes IV methylprednisolone 1g for 3 days at months 1,3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 months. 1, 3

Do not use immunosuppression if: 1, 3

• GFR <30 mL/min/1.73 m² (unless crescentic disease)
• Significant chronic histologic injury on biopsy 2

Therapies to Avoid

Do not use the following in typical IgA nephropathy: 1, 3

• Mycophenolate mofetil (MMF) - no demonstrated benefit 1
• Cyclophosphamide or azathioprine combined with corticosteroids (unless crescentic disease) 1
• Dual ACE inhibitor and ARB therapy - no additional benefit, increased hyperkalemia risk 1

Special Variant Forms Requiring Different Approaches

IgA Nephropathy with Minimal Change Disease

Treat as minimal change disease with corticosteroids if nephrotic syndrome is present with minimal change histology and mesangial IgA deposits. 1, 3

Crescentic IgA Nephropathy (>50% crescents with rapid deterioration)

Treat aggressively with corticosteroids plus cyclophosphamide, analogous to ANCA vasculitis protocols. 1, 3

IgA Nephropathy with Acute Kidney Injury

Distinguish acute tubular necrosis (supportive care only) from crescentic disease (requires immunosuppression). 2

Common Pitfalls to Avoid

• Don't delay ACE inhibitor/ARB initiation in patients with proteinuria ≥0.5 g/day while waiting for "higher" proteinuria thresholds 1
• Don't stop ACE inhibitor/ARB for modest creatinine increases up to 30% - this is expected and acceptable 1
• Don't use immunosuppression as first-line therapy - always optimize supportive care first for 3-6 months 1, 3
• Don't target outdated blood pressure goals of 140/90 mmHg - these are now considered inadequate 1, 3
• Don't use tonsillectomy - evidence does not support this approach 3

Monitoring Treatment Response

The goal is to reduce proteinuria to <1 g/day, which is associated with favorable long-term outcomes regardless of how this reduction is achieved. 1, 3 Monitor proteinuria, blood pressure, and eGFR regularly during follow-up. 1