Budesonide for IgA Nephropathy
Targeted-release budesonide (Tarpeyo) is FDA-approved for IgA nephropathy patients with UPCR >1.5 g/g who remain at high risk despite optimized supportive care, offering significant proteinuria reduction with a more favorable safety profile than systemic corticosteroids. 1
When to Use Budesonide
Budesonide should be considered for patients with persistent proteinuria ≥0.75-1 g/day after at least 90 days of maximally optimized supportive care (RAS blockade, blood pressure control to <125/75 mmHg, sodium restriction), with eGFR ≥30 ml/min/1.73m². 2, 3
Key Eligibility Criteria:
- Primary IgA nephropathy confirmed by biopsy 1
- UPCR >1.5 g/g (FDA-approved indication) 1
- Adequate trial of supportive care for 3 months minimum 2, 3
- eGFR ≥30 ml/min/1.73m² 3
Evidence for Efficacy
The NEFIGAN trial demonstrated that targeted-release budesonide 16 mg/day reduced proteinuria by 27.3% at 9 months compared to a 2.7% increase with placebo (p=0.0092), with effects sustained through follow-up. 4
Proteinuria Reduction:
- 34% reduction in proteinuria at 9 months in FDA approval studies 1
- 45% reduction at 24 months in retrospective cohort versus 11% with systemic steroids (p=0.009) 5
- 68.1% reduction at 36 months in prospective open-label study 6
Renal Function Preservation:
- eGFR preservation with +7.68% change at 12 months and +4.74% at 36 months 6
- Overall eGFR change of +0.83 ml/min/year over 36 months 6
Mechanism and Advantages Over Systemic Steroids
Targeted-release budesonide delivers active drug to the distal ileum and proximal colon, targeting the gut-associated lymphoid tissue where IgA1 dysregulation originates, while minimizing systemic absorption and adverse effects. 5, 4, 7
Safety Profile Comparison:
- Systemic corticosteroids in IgAN trials showed significantly higher serious adverse events, including 4 fatalities in the TESTING trial despite pneumocystis prophylaxis 1
- Budesonide was well-tolerated with mostly mild, reversible adverse events 5, 6
- Only 2 of 13 serious adverse events possibly related to budesonide (deep vein thrombosis and renal function deterioration during taper) 4
Treatment Protocol
Initiate budesonide 16 mg/day for 9-12 months, followed by taper to 8 mg/day or 3 mg/day for an additional 12 months. 5, 6, 4
Dosing Schedule:
- 16 mg/day for first 9-12 months 6, 4
- Taper to 3-8 mg/day for subsequent 12 months 5, 6
- Administer once daily, 1 hour before breakfast 4
- Continue optimized RAS blockade throughout treatment 4
Monitoring and Treatment Goals
Target a 50% reduction in proteinuria by 6 months and <1 g/day by 12 months, with proteinuria and eGFR monitoring every 3 months. 3, 6
Monitoring Parameters:
- Proteinuria every 3 months 8
- eGFR every 3-6 months 8
- Blood pressure at each visit 8
- Hematuria reduction (72% reduction observed at 24 months) 5
Critical Limitations and Caveats
Long-term kidney survival outcomes remain unproven, as FDA approval was based on proteinuria reduction as a surrogate endpoint rather than hard outcomes like end-stage renal disease or mortality. 1
Important Considerations:
- Legacy effect after discontinuation is not established 1, 3
- Proteinuria frequently recurs after corticosteroid cessation 3
- IgAN progression is gradual over years to decades, making short-term trial outcomes difficult to interpret 1
- Current evidence derived from limited trials; more well-designed RCTs needed 7
When NOT to Use Budesonide
Avoid budesonide in patients with eGFR <30 ml/min/1.73m² (unless rapidly progressive crescentic disease), uncontrolled diabetes with contraindications to any glucocorticoid, or inadequate trial of supportive care. 8, 3
Absolute Requirements Before Initiation:
- Must complete 90 days of maximally optimized supportive care first 2, 3
- RAS blockade titrated to maximum tolerated dose 8, 2
- Blood pressure controlled to target 8, 2
- Sodium restriction <2.0 g/day implemented 8
Alternative for Specific Populations
In Chinese patients where glucocorticoids are contraindicated, mycophenolate mofetil 1.5 g/day may be used as a glucocorticoid-sparing agent for proteinuria >1 g/day with active histologic features. 1, 8, 2