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Updated: Jun 23, 2026
Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury
Published on: February 10, 2026
Spatiotemporal transcriptomic analysis during cold ischemic injury to the murine kidney reveals compartment-specific
Srujan Singh1,2, Shishir Kumar Patel3, Ryo Matsuura3
1Center for Computational Biology, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Background:
Kidney transplantation is the preferred treatment strategy for end-stage kidney disease. Deceased donor kidneys usually undergo cold storage until kidney transplantation, leading to cold ischemia injury that may contribute to poor graft outcomes. However, the molecular characterization of potential mechanisms of cold ischemia injury remains incomplete.
Results:
To bridge this knowledge gap, we leverage 10x Visium spatial transcriptomic technology to perform full transcriptome profiling of murine kidneys subject to varying durations of cold ischemia typical in a deceased donor kidney transplant setting. We develop a computational workflow to identify and compare spatiotemporal transcriptomic changes that accompany the injury pathophysiology in a tissue compartment-specific manner. We identify proportional enrichment of oxidative phosphorylation (OXPHOS) genes with increasing duration of cold ischemia injury within the oxygen-lean inner medulla region, suggestive of atypical metabolic presentation. This is distinct in cold ischemia injury tissue compared to warm ischemia-reperfusion kidney injury tissue. Spatiotemporal trends are validated by qPCR and immunofluorescence in a larger cohort of mice.
Conclusions:
Altogether, our spatiotemporal transcriptomic analysis identifies coordinated molecular changes within metabolic pathways such as OXPHOS deep within the cold ischemic kidney, highlighting the need for increased attention to the inner medulla and potential opportunities for new insights beyond those available from superficial biopsy-focused tissue examination.
Insights
Cold storage of donor kidneys causes cold ischemia injury, impacting transplant outcomes. Spatial transcriptomics reveals altered oxidative phosphorylation in the inner medulla, suggesting new therapeutic targets for kidney transplant preservation.
Area of Science:
- Nephrology
- Transplant Surgery
- Molecular Biology
Background:
- Kidney transplantation is the gold standard for end-stage kidney disease.
- Cold storage of donor kidneys can lead to cold ischemia injury, negatively affecting graft survival.
- The molecular mechanisms underlying cold ischemia injury are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms of cold ischemia injury in deceased donor kidneys.
- To characterize spatiotemporal transcriptomic changes during cold ischemia.
- To identify tissue-specific injury patterns.
Main Methods:
- Utilized 10x Visium spatial transcriptomic technology for whole transcriptome profiling of murine kidneys.
- Developed a computational workflow for analyzing spatiotemporal transcriptomic data.
- Validated findings using quantitative PCR (qPCR) and immunofluorescence.
Main Results:
- Identified enrichment of oxidative phosphorylation (OXPHOS) genes with increasing cold ischemia duration in the inner medulla.
- Observed distinct metabolic changes in cold ischemia compared to warm ischemia-reperfusion injury.
- Demonstrated tissue compartment-specific transcriptomic alterations.
Conclusions:
- Spatiotemporal transcriptomic analysis revealed coordinated molecular changes in metabolic pathways, including OXPHOS, in cold-stored kidneys.
- Highlighted the inner medulla as a critical region affected by cold ischemia.
- Suggests potential for novel therapeutic strategies targeting inner medullary metabolism in kidney preservation.
