Abstract: TH-PO0699
Complement Activation as a Distinctive Biomarker of Pediatric Idiopathic Nephrotic Syndrome: Differentiating FSGS from Minimal Change Disease and Evidence of Podocyte Involvement
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Leenhardt, Diane, Universite de Montreal, Montreal, Quebec, Canada
- Côté, Kevin, CHU Sainte-Justine Departement de pathologie, Montreal, Quebec, Canada
- Bonnefoy, Arnaud, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Roy, Jean-Philippe, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Lachize Neanne, Lison, Universite de Montreal, Montreal, Quebec, Canada
- Sahu, Srishti, Universite de Montreal, Montreal, Quebec, Canada
- Troyanov, Stephan, Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada
- Lapeyraque, Anne-Laure, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Alexandra, Cambier, Universite de Montreal, Montreal, Quebec, Canada
Group or Team Name
- LesNephrontees.
Background
Idiopathic Nephrotic Syndrome (INS) affects 2 to 16.9 per 100,000 children worldwide. INS is classified into Minimal Change Disease (MCD), often steroid-sensitive, and Focal Segmental Glomerulosclerosis (FSGS), frequently steroid-resistant.
Previously, we identified urinary C5b-9 as a potential biomarker to differentiate FSGS from MCD in adult primary and secondary nephrotic syndromes, with FSGS patients exhibiting higher levels. However, its role in pediatric INS remains unexplored. Here, we assess urinary and plasma C5b-9 levels in pediatric INS patients with biopsy-confirmed FSGS or MCD.
For the first time we investigate complement activation on podocytes stimulated with INS patient serum to better understand C5b-9’s role in podocyte injury and in INS pathology.
Methods
We recruited only primary INS pediatric patients that had proteinuria above 1 g/g of creatinine and albuminemia below 30g/L.
Plasma and urinary C5b-9 levels were measured using ELISA. Human podocytes were stimulated with patient serum, and C5b-9 deposition was visualized using immunofluorescence microscopy. Immunohistochemistry was performed on kidney biopsies to assess C5b-9 localization.
Results
Patients with FSGS had a serum albumin of 28 ± 8 g/L and urinary protein on creatinine ratio (UPCR) of 0.85 g/mmol, while those with MCD had a higher serum albumin (30 ± 13 g/L), and UPCR (0.92g/mmol).
Urinary sC5b-9 levels were higher in FSGS patients compared to MCD (p=0.0114), while plasma levels remained similar.
Immunofluorescence revealed robust C5b-9 deposition on podocytes treated with FSGS serum, whereas those treated with MCD serum showed minimal staining.
Immunohistochemistry further supported these findings, with strong C5b-9 staining observed in FSGS kidney biopsies but absent in MCD.
Conclusion
This study is the first to demonstrate C5b-9 deposition on podocytes following stimulation with FSGS patient serum. Urinary sC5b-9 may serve as a non-invasive biomarker for distinguishing FSGS from MCD in pediatric INS and monitoring disease progression.
With further studies it may also be a good marker for active FSGS disease.
Further research is needed to clarify complement activation mechanisms and their therapeutic implications.