Sunday, April 12, 2026
JOURNAL CLUB · THIS WEEK

This Week's Paper

Annotate, discuss, and earn CME credit. Join 50 nephrologists in this week's discussion.

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Glomerular Disease

Sparsentan in IgA Nephropathy: Two-Year Outcomes from the PROTECT Trial

Dual endothelin-angiotensin receptor antagonism demonstrates durable proteinuria reduction and eGFR preservation

◆ CLINICAL BOTTOM LINE

Studied:Long-term efficacy and safety of sparsentan versus irbesartan in IgA nephropathy over 110 weeks in the PROTECT trial extension.
Found:Sparsentan reduced proteinuria by 49% versus 15% with irbesartan (p<0.001) and significantly slowed eGFR decline (-2.9 vs -3.9 mL/min/1.73m²/year).
Practice Change:Sparsentan should now be considered first-line add-on therapy for IgA nephropathy with proteinuria >1g/day, particularly in patients with progressive disease despite optimized RAS blockade.
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Editor's Annotations

"Sparsentan reduced proteinuria by 49% versus 15% with irbesartan (p<0.001)"

This is the largest proteinuria reduction seen in any IgA nephropathy trial to date.

— Dr. J. Wei

"eGFR slope was significantly less steep (-2.9 vs -3.9 mL/min/1.73m²/year)"

Clinically meaningful difference — projects to ~10 mL/min/1.73m² difference over 10 years.

— Dr. S. Kim

Discussion (50 comments)

K

Dr. Sarah Kim

Stanford Nephrology · 2 hours ago

TOP COMMENT

The 49% proteinuria reduction is impressive, but I'm concerned about the edema rate. In my practice, about 20% of patients discontinue due to fluid retention. Has anyone found strategies to mitigate this?

P

Dr. Raj Patel

Mayo Clinic · 4 hours ago

The eGFR slope data is what I find most compelling. A 1 mL/min/year difference may seem modest, but compounded over a decade, that's the difference between dialysis and not.

V

Dr. Elena Vasquez

Columbia University · 6 hours ago

Important to note the REMS program requirements. We've had to build a separate workflow for female patients of childbearing potential. The teratogenicity risk requires systematic counseling at every visit.