Abstract: FR-PO0741
From Proteinuria to Precision Nephrology: Suspected APOL1-Associated FSGS Treated with Early Sparsentan and SGLT2 Inhibition
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 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
- Sarguroh, Tauseef A., Kidney Care Center, Olympia Fields, Illinois, United States
- Abusharbak, Bisan, Kidney Care Center, Olympia Fields, Illinois, United States
- Haider, Umair, Kidney Care Center, Olympia Fields, Illinois, United States
- Khan, Shezana, Kidney Care Center, Olympia Fields, Illinois, United States
Introduction
APOL-1 associated nephropathy is an increasingly recognized cause of progressive chronic kidney disease (CKD) and focal segmental glomerulosclerosis (FSGS). Histopathologic findings may suggest APOL-1 accociated disease and prompt confirmatory genetic testing. Early initiation of kidney-protective therapies including endothelin receptor antagonism and sodium-glucose cotransporter-2 (SGLT2) inhibition may reduce proteinuria and slow CKD progression.
Case Description
A 65-year-old woman with a history of hypertension and gout was referred for evaluation of progressive proteinuria and CKD stage 3. Serum creatinine was 1.65mg/dL with estmiated glomerular filtration rate (eGFR) of 35mL/min/1.73m2. Urine protein-to-creatinine ratio was 2840 mg/g and urine albumin-to-creatine ratio was 2239 mg/g. PLA2R and HIV serologies were negative.
Native kidney biopsy demonstrated advanced nephroslcerosis with focal and segmental glmoerular sclerosis (FSGS), severe arteriosclerosis, and moderate tubulointerstitial scarring. Approximately 35% of glomeruli were globally sclerosed. Histopathology also demonstrated focal microcystic tubular dilatation and prominent thyroidization of atrophic tubules suggestive of APOL-1 associated nephropathy. No evidence of immune mediated glomerulonephritis, nodular glomerulosclerosis, or amyloidosis, was indentified. Subsequent genetic testing confirmed APOL1 risk alleles.
The patient was initiated on empaglifozin and sparsentan therapy. Patient was unable to tolerate ACEi/ARB due to prior history of allergies. Four months after treatment initiation, proteinuria improved significantly to less than 1000 mg with stabilization of kidney function.
Discussion
This case highlights the importance of recognizing morphologic clues suggestive of APOL-1 associated nephropathy in patients presenting with proteinuric CKD and advanced nephrosclerosis. Confirmatory genetic testing established the diagnosis of APOL-1 associated kidney disease and supported implementation of precision nephrology approaches. Early initiation of combined SGLT2 inhibition and endothelin receptor blockade with sparsentan was associated with marked reduction in proteinuria in four months. This case demonstrated the potential benefit of integrating histopathology, genetics, and contemporary kidney-protective therapies in the management of APOL-1 associated FSGS.