Sparsentan Reduces Urinary Immune and Inflammatory Biomarkers in IgA Nephropathy

Sparsentan significantly reduces urinary biomarkers associated with inflammation, immune cell activation, and complement activity compared with irbesartan in patients with immunoglobulin A nephropathy (IgAN), according to an analysis of the PROTECT trial being presented during American Society of Nephrology (ASN) Kidney Week 2026.

Sparsentan is a non-immunosuppressive dual endothelin and angiotensin receptor antagonist. Based on findings from the PROTECT trial (ClinicalTrials.gov Identifier: NCT03762850 ), it is approved in the United States and Europe for adults with primary IgAN at risk for disease progression.

PROTECT previously demonstrated greater proteinuria reduction and preservation of kidney function with sparsentan than with maximum-dose irbesartan over 2 years. Reductions in urinary biomarkers of inflammation and immune activation were also observed in the earlier, smaller SPARTAN study.

PROTECT was a multicenter, randomized, double-blind trial in which adults with biopsy-confirmed IgAN received sparsentan 400 mg daily or irbesartan 300 mg daily for up to 110 weeks. Participants had proteinuria of at least 1.0 g/d and an estimated glomerular filtration rate of at least 30 mL/min/1.73 m2 despite optimized renin-angiotensin system inhibitor therapy.

The biomarker analysis included 146 patients in the sparsentan group and 149 in the irbesartan group. Investigators assessed changes in four urinary biomarkers associated with macrophage activation (sCD163), B-cell activation (BAFF), complement activity (C5b-9), and inflammation (IL-6).

At week 110, sparsentan was associated with significant reductions from baseline in all four biomarkers with least-squares mean changes of −60.1% for sCD163, −64.4% for BAFF, −50.2% for C5b-9, and −45.4% for IL-6 (all P <0.001). Corresponding changes with irbesartan were −26.0% for sCD163, −45.2% for BAFF, −7.3% for C5b-9, and +8.7% for IL-6.

Between-group differences significantly favored sparsentan for sCD163 (−46.1%; P <0.001), BAFF (−34.9%; P =0.02), C5b-9 (−46.3%; P =0.032), and IL-6 (−49.7%; P <0.001). The investigators concluded that the reductions in urinary inflammatory and immune biomarkers suggest that targeting endothelin and angiotensin pathways with sparsentan has anti-inflammatory benefits for patients with IgAN.

References American Society of Nephrology (ASN) Kidney Week 2026. Abstract No. FR-OR069.