Abstract: FR-OR072
Effect of Sparsentan on Urine and Plasma Proteome of Patients with IgAN: Findings from the SPARTAN Study
Session Information
- New IgAN Therapies: Subgroups, Outcomes, and Biomarkers
October 23, 2026 | Location: Room 501, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Ju, Wenjun, University of Michigan, Ann Arbor, Michigan, United States
- Berthier, Celine C., University of Michigan, Ann Arbor, Michigan, United States
- Chaki, Sulalita, University of Michigan, Ann Arbor, Michigan, United States
- Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States
- Cheung, Chee Kay, Leicester General Hospital, Leicester, England, United Kingdom
- Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden
- Kim, Emily, University of Michigan, Ann Arbor, Michigan, United States
- Gong, Athena Yudan, University of Michigan, Ann Arbor, Michigan, United States
- Komers, Radko, Travere Therapeutics Inc, San Diego, California, United States
- Hendry, Bruce, Travere Therapeutics Inc, San Diego, California, United States
- Barratt, Jonathan, Leicester General Hospital, Leicester, England, United Kingdom
- Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
Background
SPARTAN (NCT04663204) is designed to examine how Sparsentan (SPAR) affects pathogenic pathways in IgA nephropathy (IgAN). This study aims to evaluate the impact of SPAR on patients’ non-invasive proteome, identify altered pathogenic pathways (PWYs) and mechanistic treatment response associated biomarkers.
Methods
Proteomics analysis (SomaLogic V4.1) was conducted on urine and plasma samples collected at baseline (BL) and weeks 6, 12 and 24 after initiation of SPAR treatment in patients enrolled in SPARTAN (n=12). Differencially expressed proteins (DEP) were identified between BL and after SPAR treatment (paired t-test). Enriched PWYs were identified (Metacore). PWY activity was quantified using z-scores.
Results
878 urinary DEPs were identified after 24 wks of SPAR treatment (adj. p < 0.001) versus BL, representing 53 enriched PWYs (FDR<0.05). The top 10 PWYs highlighted complement PWYs, including lectin-induced, classical, and alternative complement PWY, followed by coagulopathy and Blood coagulation PWYs. Renin-Angiotensin-Aldosterone System associated PWY was also enriched. Complement PWY activity, quantified by z-score of 16 members present in the DEPs, was significantly reduced, at all time points examined (Fig.1). The plasma proteome showed minimal alteration after SPAR treatment, suggesting the reduction of complement PWY activity is likely kidney derived. We identified urinary complement proteins that showed greater treatment responses than UPCR as potential mechanistic SPAR response biomarkers.
Conclusion
SPAR treatment was associated with broad, kidney-derived remodeling of urinary proteome, with the most prominent effects reflecting suppression of complement PWY activity across 6, 12, and 24 weeks. Our study supports complement PWY activity reduction as a downstream mechanistic feature of patients’ response to SPAR.
Changes in SPAR response - associated urinary complement PWY activity.
Funding
- Commercial Support – Travere Therapeutics