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Updated: Jul 7, 2026
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Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury
Published on: February 10, 2026
The local and systemic inflammatory transcriptome after acute kidney injury
Dmitry N Grigoryev1, Manchang Liu, Heitham T Hassoun
1Division of Allergy and Clinical Immunology, 5501 Hopkins Bayview Circle, JHAAC 3A.62, Baltimore, Maryland, 21224, USA.
Journal of the American Society of Nephrology : JASN
|February 1, 2008
Summary
Acute kidney injury (AKI) triggers inflammation and distinct genomic changes in both the kidney and lung. This study reveals shared inflammatory gene signatures and highlights IL-10 and IL-6 signaling in AKI
Area of Science:
- Nephrology
- Pulmonology
- Genomics
- Inflammation Research
Background:
- Acute kidney injury (AKI) significantly impacts extrarenal organ function, with lung dysfunction in AKI patients leading to 80% mortality.
- The lung's extensive capillary network makes it susceptible to AKI-induced systemic effects.
- Previous studies indicate a link between AKI and extrarenal organ dysfunction, but the underlying molecular mechanisms remain incompletely understood.
Purpose of the Study:
- To test the hypothesis that AKI induces a vigorous inflammatory response and distinct genomic signatures in both the kidney and lung.
- To comprehensively analyze concomitant inflammation-associated transcriptional changes in the kidney and a remote organ during AKI.
- To identify potential mediators connecting local and systemic inflammation for biomarker and therapeutic development.
Main Methods:
- Utilized a murine model of ischemic acute kidney injury (AKI).
- Performed global transcriptomic analysis and histologic examination of kidney and lung tissues at early (6 h) and late (36 h) timepoints post-ischemia.
- Analyzed changes following 60-min bilateral kidney ischemia compared to sham surgery or 30 min of ischemia.
- Conducted functional genomic analysis to identify signaling pathways involved in inflammation.
Main Results:
- Prominent global transcriptomic changes and histologic injury were identified in both kidney and lung tissues following ischemic AKI.
- Distinct inflammatory genomic signatures were observed in both organs, with significant overlap in 109 inflammation-associated genes, including Cd14, Socs3, Saa3, Lcn2, and Il1r2.
- Functional genomic analysis implicated IL-10 and IL-6 signaling in mediating distant inflammatory effects, supported by increased serum levels of these cytokines post-ischemia-reperfusion.
- Transcriptomic changes were more pronounced after 60-min ischemia compared to shorter ischemia or sham procedures.
Conclusions:
- AKI induces a significant inflammatory response with shared genomic signatures in both the kidney and remote organs like the lung.
- Interleukin-10 (IL-10) and Interleukin-6 (IL-6) signaling pathways are likely involved in the systemic inflammatory effects of AKI.
- Transcriptomic analysis of AKI provides a valuable discovery tool for identifying novel biomarkers and potential therapeutic targets for managing AKI-induced systemic inflammation.
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