Abstract: TH-PO0545
A Case on Emerging Therapies in Refractory IgAN
Session Information
- Glomerular Diseases: IgAN, IgA Vasculitis, and More
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
- Asaolu, Gideon, Northeast Georgia Health System Inc, Gainesville, Georgia, United States
- Aggarwal, Deepak K., Northeast Georgia Health System Inc, Gainesville, Georgia, United States
Introduction
IgA nephropathy (IgAN) remains the most common primary glomerulonephritis and a leading cause of progressive chronic kidney disease, with up to 50% of patients progressing to kidney failure within 10 years of diagnosis. Therapeutic options for patients with persistent proteinuria despite conventional immunosuppression remain limited. We report a case of biopsy-proven high-risk IgAN with persistent nephrotic-range proteinuria despite standard therapy, demonstrating improvement following use of novel targeted agents.
Case Description
54-year-old man with biopsy-proven IgAN diagnosed in September 2017 (Oxford MEST-C score: M1E0S1T1C1) presented with 24-hour proteinuria of 2,343 mg/day. Kidney biopsy showed 46 glomeruli with 21.7% global sclerosis, 13.0% segmental sclerosis, 4 cellular crescents, and 25% interstitial fibrosis/tubular atrophy. Initial treatment included Mycophenolic acid mycophenolate mofetil from 2017–2021. Proteinuria was controlled - nadir of 245 mg/day by February 2021. Proteinuria relapsed to 1,191 mg/day by February 2023 and reaching 3,750 mg/g on spot proteinuria by January 2025. Managed with telmisartan, omega-3 fatty acids, dapagliflozin. Dapagliflozin was temporarily discontinued due to financial constraints, with minimal proteinuria response upon resumption. Targeted-release budesonide and Sparsentan were initiated, telmisartan discontinued. Spironolactone was later added for persistent proteinuria. Although modest improvement was observed (spot proteinuria - 2,307 mg/g in December 2025 and 2,000 mg/g in February 2026), clinically significant proteinuria persisted.
Given ongoing disease, budesonide was tapered and discontinued, and Sibeprenlimab-szsi was initiated on March 2026, with continuation of sparsentan and dapagliflozin. Early follow-up demonstrated reduction in 24-hour proteinuria to 1,430 mg/day from 2,284 mg/day prior to initiation, with the trajectory suggesting ongoing improvement.
Discussion
This case highlights the evolving role of sequential pathway-specific therapy in refractory IgAN. Despite failure of conventional immunosuppression and incomplete response to sparsentan and targeted-release budesonide, the addition of sibeprenlimab-szsi was associated with a substantial reduction in proteinuria. As an anti-APRIL monoclonal antibody, sibeprenlimab targets upstream production of galactose-deficient IgA1 and immune complex formation, represents a distinct approach from glucocorticoid-based therapies.