Abstract: TH-PO0302
Deep Phenotyping of Serial Kidney Biopsies in a Mouse Model of Nephrotoxic Serum-Induced Glomerulonephritis
Session Information
- Glomerular Diseases: Cell Biology
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
- Burmakin, Mikhail, Alvolab AB, Stockholm, Sweden
- Ebbestad, Robin, Magnephy AB, Stockholm, Sweden
- Jin, Yi, Alvolab AB, Stockholm, Sweden
- Unnersjö-Jess, David, Magnephy AB, Stockholm, Sweden
- Olauson, Hannes, Alvolab AB, Stockholm, Sweden
Background
Kidney disease involves dynamic processes where longitudinal monitoring is typically limited to blood and urine biomarkers. We aimed to apply a novel method for serial kidney biopsies in the nephrotoxic serum (NTS) mouse model to allow for deep phenotyping of disease progression and therapeutic response on the tissue level within the same animal.
Methods
Using the serial kidney biopsy technique described by Mao et al. (PMID: 34395545), we conducted two studies in the NTS model. Study 1 determined optimal biopsy timing: Group A (baseline, day 1, and 5) and Group B (baseline, day 3, and 10). Study 2 evaluated therapeutic interventions using baseline, day 3, and 10 biopsies. Treatment groups included healthy controls, NTS+vehicle, NTS+dexamethasone, and NTS+an experimental mRNA-based therapeutic. Biopsies were analyzed using standard histology (HE, PAS, Sirius Red), nanoscale 3D microscopy with AI-powered analysis, and Xenium spatial transcriptomics.
Results
In Study 1, histology and 3D microscopy with AI-powered analysis revealed acute podocyte injury at day 1, which showed a gradual normalization over 10 days. Based on these kinetics, Study 2 utilized the day 3 and 10 windows for drug evaluation. Both dexamethasone and mRNA treatments significantly reduced proteinuria and injury biomarkers and increased GFR compared to vehicle-treated NTS mice. Deep phenotyping and spatial transcriptomics from serial biopsies confirmed that both interventions preserved glomerular architecture and reduced inflammatory gene expression signatures throughout the disease course.
Conclusion
Serial kidney biopsies enable high-resolution, longitudinal monitoring of pathology and transcriptomics in experimental models of kidney disease. This approach adheres to the 3R principle by eliminating the need to sacrifice mice at different timepoints and provides a powerful platform for evaluating novel therapeutics for the treatment of kidney disease.