Abstract: TH-PO0351
Temporal Changes in the Prognostic Value of Proteinuria in Alport Syndrome Mouse Models
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Tsuhako, Haruki, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Suico, Mary Ann, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Shuto, Tsuyoshi, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
- Kai, Hirofumi, Department of Molecular Medicine, Graduate School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
Background
Alport syndrome (AS) is an inherited kidney disease caused by mutations in the type IV collagen genes COL4A3, COL4A4, and COL4A5. Progressive proteinuria and renal dysfunction are hallmark features of AS, and renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used as symptomatic treatment. However, the extent to which proteinuria predicts survival at different disease stages remains unclear. Here, we conducted a longitudinal study to investigate the relationship between proteinuria and survival in AS mouse models with distinct genetic backgrounds.
Methods
C57BL/6J-background Col4a5-G5X mice (n=14), representing a slowly progressive model, and 129X1/SvJ-background Col4a3 knockout mice (n=44), representing a rapidly progressive model, were included in this study. Urine samples were collected longitudinally using metabolic cages, and urinary protein levels were quantified. The association between proteinuria and survival was assessed using Spearman’s rank correlation analysis. Kaplan-Meier survival analysis was performed after stratifying mice into high- and low-proteinuria groups.
Results
In C57BL/6J Col4a5-G5X mice, proteinuria showed only a weak correlation with survival until 26 weeks of age. However, a strong negative correlation emerged between 27 and 31 weeks of age (Spearman’s ρ < −0.5). At 28 weeks, mice with high proteinuria showed significantly shorter survival than those with low proteinuria. These data suggest that approximately 27 weeks of age marks a potential transition point toward rapid progression to massive proteinuria and low survival in the C57BL/6J Col4a5-G5X model. In contrast, 129X1/SvJ Col4a3 knockout mice exhibited a strong negative correlation between proteinuria and survival as early as 4 weeks of age.
Conclusion
The prognostic significance of proteinuria in Alport syndrome varied substantially according to genetic background and disease stage. Notably, the C57BL/6J Col4a5-G5X model enables the investigation of pathological alterations preceding the rapid progression to overt massive proteinuria, making it a valuable model for studying early disease mechanisms and for the identification of early biomarkers and therapeutic targets.