Abstract: FR-PO0146
Spatially Resolved Kidney Transcriptome Signatures in Rat Models of Trauma-Induced AKI
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Isnard, Pierre, Institut Necker Enfants Malades, Paris, Île-de-France, France
- Martinez, Thibault, Hopital d'Instruction des Armees Percy, Clamart, Île-de-France, France
- Humphreys, Benjamin D., Washington University in St Louis, St. Louis, Missouri, United States
- Libert, Nicolas, Hopital d'Instruction des Armees Percy, Clamart, Île-de-France, France
Background
Trauma is a major public health burden worldwide, and is the leading cause of death in young patients. Trauma-induced acute kidney injury (AKI) significantly impacts patient outcomes, with hemorrhagic shock (HS) and rhabdomyolysis (RM) being primary contributors. Both insults have been studied separately, but their combined effect on AKI is poorly understood. The goal of this study was to characterize the kidney’s transcriptomic landscape under conditions of RM, HS, and their combination (RM-HS) in a rat model, to identify key molecular drivers of trauma-induced AKI.
Methods
A rat model was subjected to RM, HS, or RM-HS, and kidney tissue was collected at early time points for transcriptomic analysis. Gene expression was profiled using both bulk RNA-sequencing and spatial transcriptomics (ST) to assess regional differences in the kidney, including cortex, glomeruli, corticomedullary junction (CMJ), and medulla and explore the molecular mechanisms underlying AKI.
Results
Bulk and ST revealed RM as the dominant driver of transcriptional changes with RM-HS leading to a catastrophic response and a high mortality rate. We identified significant involvement of hypoxia, reactive oxygen species, unfolded protein response, and apoptosis pathways as key drivers of injury. Region-specific analyses highlighted the CMJ as a critical site of injury, where lipid metabolism dysregulation and ferroptosis were prominent. Notably, perilipin 2 (PLIN2), a lipid droplet-associated protein, emerged as a key marker of RM and RM-HS, correlating with metabolic dysfunction and injury severity.
Conclusion
RM is the primary driver of transcriptomic changes in trauma-induced AKI. Lipid metabolism and ferroptosis emerged as central contributors to AKI in trauma conditions. These insights pave the way for the development of new therapeutic strategies and biomarkers aimed at reducing AKI severity in trauma patients.