Kidney Week

Abstract: TH-PO0496

Predictors of Response and Tolerability of Sparsentan in a Real-World IgAN Cohort

Session Information

• Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - IgAN
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Cara, Anila, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Anila Cara, MD

• Vargas-Brochero, Maria J., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Maria J. Vargas-Brochero, MD, MS

• Juanet, Cristián, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Cristián Juanet, MD

• Berti, Gian Marco, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Gian Marco Berti, MD, PhD

• Russo, Ilario, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Ilario Russo

• Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Fernando C. Fervenza, MD, PhD, FASN

• Zand, Ladan, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Ladan Zand, MD

Background

Sparsentan, a dual endothelin type A and angiotensin II type 1 receptor antagonist (DEARA), has demonstrated antiproteinuric efficacy in randomized trials of IgA nephropathy (IgAN). However, real-world response patterns and predictors remain poorly characterized

Methods

In this single-center observational study, 38 adults with biopsy-proven IgAN were assessed at baseline,3,6,9,and 12 months. The primary outcome was ≥50% proteinuria reduction. Predictors of response were evaluated using logistic regression at each time point with particular focus on the 9-month landmark.

Results

The cohort was predominantly white (76%), and male (63%) with a mean age of 45±13 years. Median baseline eGFR was 42.2 mL/min/1.73m2 [31.9–54.8], and 23.7% of the patients had an eGFR < 30 ml/min/1.73 m2. The median proteinuria was 2066 mg/24h [1215–4074]. Time from kidney biopsy to initiation of sparsentan was 11.3 months [5.0-51.7], and median follow-up duration was 11 months [5.25-17]. All patients were receiving RAAS inhibition and 58% were on SGLT2 inhibitors at initiation. Sparsentan induced sustained proteinuria reduction over time, with no significant interaction with background immunosupression. In mixed-effects models, proteinuria declined by 50% at 9 months, while eGFR showed a chronic decline of −2.5 mL/min/1.73 m2/year (p=0.188). At 9 months, baseline hematuria (OR 10.00; 95% CI 1.28–78.12; p = 0.028) and higher sBP (OR 4.30; 95% CI 1.02–18.10; p=0.047) were independently associated with response. Sparsentan was well tolerated; discontinuation occurred in 10.5%, including two cases due to mild and reversible elevations in liver enzymes.

Conclusion

In routine practice, sparsentan provides durable antiproteinuric benefit with relatively stable renal trajectories despite advanced baseline disease. Our findings suggest that both hemodynamic and inflammatory determinants are predictors of response supporting a physiology-based approach to patient stratification