Abstract: SA-PO0711
More Than a Typical Postinfectious Glomerulonephritis: The Complement Connection
Session Information
- Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
October 24, 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
- Chrabol, Conrad, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Menon, Aiswarya, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Introduction
C3 glomerulonephritis (C3GN) is a rare glomerulonephritis characterized by dysregulated activation of the alternative complement pathway. It is diagnosed in 1–3 individuals per million annually, although increasing disease recognition and broader utilization of kidney biopsy may lead to rising incidence. Complement inhibitors have shown promising results in reducing proteinuria and slowing decline in eGFR. However, questions regarding long-term outcomes, patient selection, and duration of therapy remain unanswered. Continued investigation into complement dysregulation in C3GN may provide broader insight into the pathogenesis and treatment of more common diseases in which similar pathways are implicated.
Case Description
A 55-year-old female with hypertension and obesity presented with several weeks of lower extremity edema followed by acute onset fever and chills. Vitals were notable for high-grade fever and sinus tachycardia. Labs showed a marked leukocytosis (41.4), elevated creatinine (1.74), and profound hypoalbuminemia (0.6). Blood cultures grew S. pyogenes. Additional workup revealed microscopic hematuria, nephrotic-range proteinuria (UPCR 18.8), and low C3 (68). Immunofixation identified a faint IgG kappa band that was not apparent on repeat testing. Renal biopsy was performed. Light microscopy showed marked mesangial prominence with nodule formation, along with widespread acute tubular injury. Immunofluorescence revealed dominant C3 staining (2–3+) in the mesangium, capillary loops, and tubular basement membranes, with only trace IgA deposition. Electron microscopy demonstrated a thickened GBM, scattered mesangial deposits, and rare subepithelial "humps”. Overall findings were most consistent with C3GN, sepsis-related tubular injury, and nodular glomerulosclerosis of unclear etiology. Although proteinuria improved with treatment of infection, it persisted in the nephrotic range.
Discussion
C3GN arises from inherited or acquired abnormalities, often mediated by autoantibodies targeting complement regulatory proteins. Infections may serve as a “second hit” that triggers overt disease manifestation. Monoclonal gammopathy must be excluded as a paraprotein may drive complement activation. Two complement inhibitors are currently approved and should be considered in moderate to severe disease. Ongoing clinical trials may further expand therapeutic options and deepen our understanding of this complex and evolving disease.