Abstract: FR-PO0920
Isatuximab for Refractory Primary FSGS
Session Information
- Glomerular Case Reports: Lupus, FSGS, Complement, and More
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Samant, Samira Mahesh, The Permanente Medical Group Inc, Santa Clara, California, United States
- Poyan Mehr, Ali, The Permanente Medical Group Inc, Santa Clara, California, United States
- Taneja, Nidhika, The Permanente Medical Group Inc, Santa Clara, California, United States
Introduction
Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome, named for characteristic histologic scarring of part of the glomerulus. Primary, or idiopathic, FSGS is typically treated with immunosuppressants, mainly glucocorticoids and calcineurin inhibitors. Failure to achieve remission is associated with worse outcomes and higher risk of progression to end-stage kidney disease. Novel therapies such as anti-CD38 antibodies are being explored in such cases.
Case Description
A 40-year-old male with a history of gastrointestinal stromal tumor presented with weeks of progressive lower extremity pitting edema to his hips. 24-hour urine collection showed 6.2 g of proteinuria, serum creatinine was 0.76 mg/dL, and serum albumin was 3.8 g/dL. Infectious and autoimmune workup was nonrevealing. Renal biopsy showed minimal change disease. He achieved partial remission with steroids, tacrolimus, and mycophenolate mofetil (MMF), and eventually stabilized on prednisone and tacrolimus, with losartan, empagliflozin, spironolactone, and atorvastatin. A year later he self-discontinued tacrolimus and developed severe edema; renal biopsy revealed FSGS with diffuse podocytopathy. Genetics evaluation was negative. UPCR was 6.24 with serum albumin 2.8 g/dL, and he resumed tacrolimus. Due to incomplete response, MMF was reintroduced, then rituximab. After rituximab induction, UPCR was 3.14, albumin 3 g/dL. Given his lack of response to classic therapies, he was agreeable to and started on isatuximab. After the first cycle, UPCR improved to 1.16, albumin to 4.2 g/dL, and creatinine stable; his edema resolved. MMF and tacrolimus were weaned off after 3 months, and he received repeat isatuximab infusions 6 months later, with followup UPCR 1.19. He is planned for another cycle in 6 months, and continues to demonstrate good response.
Discussion
Amongst the novel therapies being explored in the management of relapsing primary FSGS, anti-plasma cell antibodies are emerging as an alternative treatment option. CD-38 targeting antibodies such as isatuximab have been studied in the treatment of immune-mediated diseases, including primary FSGS, demonstrating either total remission or improvement in disease severity in cases refractory to conventional therapies. Further research is needed to determine optimal treatment regimens and dosing frequency, better study their efficacy, and the potential risk of adverse effects.