Abstract: FR-PO0910
Marked Proteinuria Reduction in a Patient with APOL1-Associated Primary FSGS Treated with Prednisone
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
Author
- Elharrif, Khalid, The University of Chicago, Chicago, Illinois, United States
Introduction
Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and progressive kidney disease. In individuals of African ancestry, the presence of APOL1 risk alleles is strongly associated with the development of primary FSGS. While APOL1-associated FSGS is often thought to confer a poor prognosis and resistance to immunosuppression, a subset of patients may still respond favorably to therapy. This case highlights the successful treatment of an APOL1-positive FSGS patient with corticosteroids.
Case Description
A 54-year-old African American female with a past medical history of hypertension presented to the nephrology clinic with bilateral lower extremity edema. Laboratory workup revealed a serum creatinine of 1.2 mg/dL (eGFR 54 mL/min), UPC ratio of 8.0 g/g and hypoalbuminemia with a serum albumin of 2.0 g/dL. A kidney biopsy showed primary FSGS. Genetic testing revealed the presence of high-risk APOL1 variants (G1/G1). Despite the association of these alleles with treatment resistance, she was initiated on prednisone therapy. Over several weeks, her proteinuria decreased to 2.5 g/g, with concurrent improvement in edema and serum albumin levels. She was continued on a tapering course of prednisone and started on losartan for proteinuria reduction and blood pressure control. Her kidney function remained stable, and proteinuria remained in the subnephrotic range on follow-up, indicating a favorable partial remission.
Discussion
FSGS is a histopathological pattern of glomerular injury that may arise from various etiologies, including genetic mutations. APOL1 gene variants are among the most significant risk factors for primary FSGS in individuals of African descent. While the pathogenesis remains under investigation, these variants are believed to confer cytotoxic gain-of-function effects on podocytes, leading to glomerular scarring and proteinuria. Historically, APOL1-associated FSGS has been associated with resistance to glucocorticoids and rapid progression to end-stage renal disease. However, emerging evidence suggests that steroid responsiveness is still possible, particularly in patients without advanced chronic kidney disease at diagnosis. This case supports the role of immunosuppression, even in genetically predisposed individuals. Further studies are warranted to better stratify risk and guide management in this unique population.