Can we start Tarpeyo (sparsentan) in a 45‑year‑old man with IgA nephropathy and impaired renal function (eGFR ~40–45 mL/min/1.73 m²) who is already on dapagliflozin and telmisartan but still has elevated proteinuria?

Should You Start Sparsentan (Tarpeyo) in This Patient?

No, you should not start sparsentan (note: sparsentan is FILSPARI®, not Tarpeyo—Tarpeyo is budesonide) in this patient at this time, because the current KDIGO 2021 guidelines classify sparsentan as an investigational agent under evaluation and recommend prioritizing enrollment in clinical trials rather than routine clinical use. 1

Critical Clarification: Drug Name Confusion

• Tarpeyo is the brand name for targeted-release budesonide (an enteric-coated corticosteroid), not sparsentan 2
• Sparsentan is marketed as FILSPARI®, a dual endothelin-angiotensin receptor antagonist 3, 4
• These are entirely different medications with different mechanisms of action

Current Guideline Position on Sparsentan

KDIGO 2021 Stance

• The most recent KDIGO 2021 guidelines explicitly list sparsentan among "new therapies for high-risk IgAN patients currently being evaluated" rather than established treatments 1
• The guidelines recommend that patients be "offered participation in a disease registry and clinical trials, whenever available" for access to agents like sparsentan 1
• Sparsentan is mentioned alongside other investigational drugs (atrasentan, complement inhibitors, B-cell therapies) as potentially augmenting supportive care, but not yet recommended for routine use 1

Why Guidelines Remain Cautious

• The PROTECT trial results were published in November 2023—after the 2021 KDIGO guidelines were finalized 3
• While sparsentan received regulatory approval in the US, EU, Switzerland, and UK in 2024, guideline updates typically lag behind FDA/EMA approvals by 1-3 years 3
• The PROTECT study did not evaluate sparsentan in combination with SGLT2 inhibitors, which your patient is already receiving 5

What You Should Do Instead

Step 1: Optimize Current Supportive Care (Next 90 Days)

• Continue dapagliflozin: This SGLT2 inhibitor has proven efficacy in IgAN, reducing the primary composite kidney endpoint by 71% (HR 0.29) in the DAPA-CKD trial 6
• Maximize telmisartan dose: Uptitrate to 80 mg daily if not already at maximum, targeting proteinuria <1 g/day even if blood pressure is controlled 1, 7
• Strict blood pressure control: Target systolic BP <120 mmHg (or <125/75 mmHg given elevated proteinuria) 7, 2
• Sodium restriction: Limit dietary sodium to <2 g/day (<90 mmol/day) to enhance antiproteinuric effects 1, 7

Step 2: Reassess After 90 Days of Optimized Care

• Measure proteinuria at 3 months: If proteinuria remains >0.75–1 g/day despite maximal supportive care, the patient qualifies as high-risk 1, 7
• Verify eGFR threshold: With eGFR 40–45 mL/min/1.73 m², the patient is above the eGFR ≥30 threshold where immunosuppression may be considered, though adverse effects are more likely below eGFR 50 1

Step 3: Consider Guideline-Endorsed Options First

If proteinuria persists >1 g/day after 90 days:

1. Targeted-release budesonide (Tarpeyo) is now considered first-line immunosuppression over systemic corticosteroids due to superior safety 2

   • This is the actual "Tarpeyo" you may have been asking about
   • Preferred over the older Pozzi protocol (IV methylprednisolone + oral prednisone) 2

2. Systemic corticosteroids (6-month Pozzi protocol) if budesonide unavailable 1, 7

   • Caution: Your patient's eGFR 40–45 mL/min/1.73 m² places him in a higher-risk category for steroid-related adverse events 1
   • Absolute contraindications include eGFR <30, diabetes, obesity (BMI >30), active/latent infections 1, 7

3. Clinical trial enrollment for access to sparsentan or other novel agents 1, 7

Emerging Real-World Evidence on Sparsentan

Recent Data Supporting Future Use

• A 2025 real-world study showed sparsentan added to SGLT2 inhibitors achieved 62% reduction in proteinuria at 14 weeks in 23 IgAN patients already on maximum RAS blockade and SGLT2 inhibitors 5
• Median baseline UPCR was 1.5 g/g, dropping to 0.60 g/g after 14 weeks 5
• No drug-related serious adverse events were reported 5
• This suggests sparsentan may have additive benefit even in patients already on dapagliflozin, though this remains investigational 5

Mechanism of Action

• Sparsentan is a dual endothelin type A and angiotensin II type 1 receptor antagonist, providing more complete blockade than ARBs alone 4, 8
• It directly impacts glomerular hemodynamics through mechanisms that telmisartan and dapagliflozin do not fully address 4, 8
• The PROTECT trial showed sparsentan reduced proteinuria more than maximum-dose irbesartan (400 mg) over 2 years 3

Critical Pitfalls to Avoid

• Do not start any immunosuppression (including sparsentan if you obtain it off-label) before completing ≥90 days of optimized supportive care with maximum-dose ARB, SGLT2 inhibitor, BP control, and sodium restriction 1, 7
• Do not discontinue telmisartan if creatinine rises ≤30% from baseline; this modest rise predicts better long-term renal protection 7
• Do not use dual ACE-inhibitor + ARB therapy; it increases adverse events without additional benefit 7
• Do not rely solely on eGFR or histologic features (MEST-C score, crescent count) to trigger immunosuppression; persistent proteinuria after optimized supportive care is the key decision point 1, 7, 2

When Sparsentan May Become Standard of Care

• Expect updated KDIGO guidelines in 2026–2027 to incorporate post-2023 sparsentan data 3
• Some experts anticipate sparsentan will eventually supplant ARBs as first-line therapy for proteinuria reduction in IgAN, but this is not yet guideline-endorsed 8
• For now, sparsentan remains best accessed through clinical trials or managed access programs in select countries 5