What is the recommended induction and maintenance treatment regimen for IgA nephropathy, including steroid dosing, taper schedule, and steroid‑sparing agents?

Induction and Maintenance Treatment for IgA Nephropathy

For patients with IgA nephropathy at risk of progression (proteinuria ≥1 g/day despite 3-6 months of optimized RAS blockade and eGFR >50 mL/min/1.73 m²), use reduced-dose methylprednisolone 0.4 mg/kg/day (maximum 32 mg/day) for 2 months, then taper by 4 mg/day each month over 6-9 months, combined with antimicrobial prophylaxis against Pneumocystis jirovecii. 1

Initial Assessment and Risk Stratification

Before initiating immunosuppression, confirm:

• Persistent proteinuria ≥1 g/day after 3-6 months of maximally tolerated RAS inhibitor therapy
• eGFR >50 mL/min/1.73 m² (avoid immunosuppression if eGFR <30 unless crescentic disease)
• Blood pressure optimized to <130/80 mm Hg (or <125/75 mm Hg if proteinuria >1 g/day) 2, 3, 4
• No contraindications: active infection, diabetes/prediabetes, obesity, latent tuberculosis or hepatitis B, uncontrolled psychiatric illness, osteoporosis, or cataracts 1

Induction Regimen (First-Line)

Reduced-Dose Systemic Corticosteroids (Where Nefecon Unavailable)

Dosing schedule:

• Months 1-2: Methylprednisolone 0.4 mg/kg/day (maximum 32 mg/day) as single daily dose
• Months 3-9: Taper by 4 mg/day each month until discontinuation
• Total duration: 6-9 months 1, 5

This reduced-dose regimen from the TESTING trial demonstrated significant reduction in 40% eGFR decline, kidney failure, and kidney death compared to placebo, with substantially fewer serious adverse events than the original full-dose protocol (0.6-0.8 mg/kg/day) 1, 5.

Targeted-Release Budesonide (Nefecon) - Where Approved

Alternative first-line option:

• 16 mg once daily for 9 months 1
• This formulation delivers budesonide to the ileum, targeting mucosal immune dysfunction with reduced systemic exposure
• FDA-approved in the United States based on proteinuria reduction, though long-term kidney outcome data are pending 1

Mandatory Prophylaxis During Corticosteroid Treatment

• Pneumocystis prophylaxis: Trimethoprim-sulfamethoxazole during first 12 weeks (essential with any corticosteroid regimen) 1, 5
• Antiviral prophylaxis: For hepatitis B carriers 1
• Gastroprotection: Proton pump inhibitor 1
• Bone protection: Per national osteoporosis guidelines 1

Maintenance Therapy

Renin-Angiotensin System Blockade (Lifelong)

All patients require:

• ACE inhibitor OR ARB at maximally tolerated dose (not both together unless using sparsentan) 1
• Continue indefinitely even after completing immunosuppression
• Target proteinuria <1 g/day 2, 3, 4

SGLT2 Inhibitors (Recommended Addition)

For patients at risk of progression:

• Add SGLT2 inhibitor regardless of diabetes status 1
• Provides additional kidney protection independent of immunosuppression
• Can be initiated alongside or after corticosteroid therapy

Sparsentan (Where Approved)

Alternative to standard RAS blockade:

• Dual endothelin-1 and angiotensin II receptor antagonist
• Replaces (not added to) ACE inhibitor/ARB 1
• Consider for patients requiring enhanced antiproteinuric effect

Special Circumstances

Crescentic IgA Nephropathy (>50% Crescents with Rapid Deterioration)

Aggressive induction required:

• Treat analogously to ANCA vasculitis 2, 3, 4
• High-dose corticosteroids PLUS cyclophosphamide 6, 7
• Regimen: Methylprednisolone 1 g IV daily for 3 days, then oral prednisone 0.8 mg/kg initially, reducing to 0.4 mg/kg after 4 weeks, PLUS cyclophosphamide 1.5 mg/kg until response plateaus (typically 12-25 weeks) 6
• After response, maintain on low-dose prednisone (5-7.5 mg) plus azathioprine 1 mg/kg for 2 years 6

IgA Nephropathy with Minimal Change Disease Features

Treat as minimal change disease:

• High-dose prednisone 1 mg/kg/day (maximum 80 mg) or 2 mg/kg alternate days (maximum 120 mg) 8
• Continue until complete remission (minimum 4 weeks, maximum 16 weeks)
• Taper by 5 mg every 1-2 weeks over 6 months total duration 8

Patients with eGFR <50 mL/min/1.73 m²

Avoid immunosuppression unless:

• Crescentic disease with rapid deterioration 2, 4
• Risk of serious adverse events substantially increases below this threshold 1

Agents NOT Recommended

The following have insufficient evidence or demonstrated lack of benefit:

• Mycophenolate mofetil (except possibly in Chinese patients as steroid-sparing agent) 2, 4, 1
• Cyclophosphamide or azathioprine (except crescentic disease) 2, 4
• Calcineurin inhibitors 1
• Fish oil 3, 4
• Antiplatelet agents 4
• Tonsillectomy (except in Japan) 4, 1
• Rituximab 1

Monitoring During Treatment

Monthly during induction:

• Serum creatinine and eGFR
• Proteinuria (24-hour urine or protein-creatinine ratio)
• Blood pressure
• Adverse effects (infection, hyperglycemia, psychiatric symptoms, bone density)

Every 3-6 months during maintenance:

• Same parameters as above
• Consider repeat kidney biopsy if no response after 6 months or unexpected deterioration

Critical Pitfalls to Avoid

1. Starting immunosuppression without adequate RAS blockade trial: Must document 3-6 months of optimized supportive care first 2, 3, 4, 1

2. Using full-dose corticosteroids (0.6-0.8 mg/kg): The TESTING trial was paused due to excess serious infections with this regimen; use reduced dose (0.4 mg/kg) only 1, 5

3. Omitting Pneumocystis prophylaxis: Mandatory with any corticosteroid regimen to prevent life-threatening infection 1, 5

4. Treating low-risk patients: Reserve immunosuppression for proteinuria ≥1 g/day despite optimal supportive care 2, 3, 4, 1

5. Immunosuppressing advanced CKD: Avoid if eGFR <30 mL/min/1.73 m² unless crescentic disease 2, 4

6. Premature discontinuation of RAS blockade: Continue indefinitely as maintenance therapy even after completing immunosuppression 1