Kidney Week

Abstract: FR-PO0725

When Inflammation Meets Genetics: A Suspected Second-Hit Trigger of APOL1-Carrier-Associated FSGS

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

• Pico-Ramirez, Alexandra C., Universidad de Puerto Rico Escuela de Medicina, San Juan, Puerto Rico

Alexandra C. Pico-Ramirez, MD

• Vazquez Morales, Emily, Universidad de Puerto Rico Escuela de Medicina, San Juan, Puerto Rico

Emily Vazquez Morales, MD

• Ocasio Melendez, Ileana E., Universidad de Puerto Rico Escuela de Medicina, San Juan, Puerto Rico

Ileana E. Ocasio Melendez, MD, FASN

• Vega-Colon, Jesus Daniel, Universidad de Puerto Rico Escuela de Medicina, San Juan, Puerto Rico

Jesus Daniel Vega-Colon, MD

Introduction

Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and represents a heterogeneous pattern of podocyte injury associated with progressive chronic kidney disease. Kidney biopsy and genetic testing are increasingly important in defining disease etiology and guiding therapy. We present a case of severe nephrotic syndrome with preserved renal function diagnosed as primary FSGS in a patient with APOL1 risk allele carrier status, highlighting a possible preceding inflammatory “second hit” triggering disease onset.

Case Description

A 48-year-old male with hypertension, hyperlipidemia, and neovascular glaucoma presented with one month of progressive abdominal distension and lower extremity edema. Physical examination revealed hypertension, decreased bibasilar breath sounds, and pitting abdominal wall and lower extremity edema. Laboratories revealed iron deficiency anemia, severe hypoalbuminemia, metabolic alkalosis, preserved renal function, and nephrotic-range proteinuria of 16.7 g/g. Serologic workup, including ANA, complement levels, hepatitis panel, HIV, serum and urine protein electrophoresis, was unrevealing. Several months prior, he was hospitalized for acute vision changes and lower extremity weakness concerning for a demyelinating process. Despite extensive neurologic evaluation, no definitive diagnosis was established. He was treated with intravenous loop diuretics, an angiotensin receptor blocker, and sodium-glucose cotransporter-2 inhibition, leading to mild improvement. Outpatient native kidney biopsy consistent with primary FSGS with mild global glomerulosclerosis and interstitial fibrosis/tubular atrophy. Genetic testing was negative for pathogenic monogenic FSGS mutations but revealed APOL1 risk allele carrier status.

Discussion

This case highlights the importance of integrating histopathology, clinical presentation, and genetic testing in nephrotic syndrome evaluation. Given the temporal relationship in this patient’s presentation, it also suggests that inflammatory events may serve as environmental triggers for FSGS in genetically susceptible individuals. Recognition of this “second-hit” phenomenon may improve diagnostic precision, support earlier immunosuppressive therapy, and refine risk stratification in APOL1-associated glomerular disease