Abstract: TH-PO0537
Refractory Nephrotic Syndrome Treated with Off-Label Obinutuzumab
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
- Almanzar, Mirtha Camila, Columbia University, New York, New York, United States
- Koirala, Priscilla, Columbia University, New York, New York, United States
- Navarro Torres, Mariela, Columbia University, New York, New York, United States
Introduction
Refractory nephrotic syndrome (NS) remains a major therapeutic challenge and is associated with recurrent hospitalizations, severe infections, progressive kidney failure, and substantial patient morbidity. Patients with NS who fail standard therapies often require continued immunosuppression with significant toxicity risks. We present two cases of refractory NS with multiple relapses despite guideline-directed therapy that achieved remission after treatment with obinutuzumab.
Case Description
Case 1: A 60-year-old man presented with NS with 8g/g of proteinuria, SAlb 2 mg/dl, where a kidney biopsy (KB) showed minimal change disease (MCD). Initially received high-dose corticosteroids, but due to side effects, required a rapid steroid taper. He remained severely nephrotic and developed AKI. He was subsequently treated with rituximab, but was later hospitalized due to refractory anasarca requiring IV diuretics. Although kidney function partly improved, nephrotic-range proteinuria persisted. Three months later, the patient failed to achieve remission and B-cell depletion, which prompted treatment with obinutuzumab, resulting in complete remission within approximately six weeks.
Case 2: A 70-year-old man with HTN and chronic NSAID use presented with anasarca. Evaluation revealed 27g/g of proteinuria with negative serologies. KB revealed MCD with acute tubular necrosis and minimal IFTA. Due to severe volume overload refractory to intravenous diuresis, he required iHD. NS was refractory to corticosteroid, MPA, and plasma exchange (PLEX) followed by rituximab. A repeat kidney biopsy showed to 40% IFTA, FSGS tip variant, and IgG podocyte “dusting”. He received obinutuzumab, achieving HD discontinuation after 1 year, with an SCr of 1.7 mg/dl and 2.9 g/g proteinuria on follow-up.
Discussion
Refractory NS carries high morbidity and risk for progression to kidney failure. Obinutuzumab, a type II anti-CD20 monoclonal antibody, has shown efficacy in rituximab-resistant lymphoproliferative disorders and lupus nephritis, with reports supporting its use in refractory NS. These cases suggest a potential role for earlier use of obinutuzumab in older patients and those with treatment-resistant disease who often develop worse outcomes. Larger studies are needed to better define its efficacy, safety, and long-term outcomes in refractory NS.