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Updated: May 10, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
The conundrum of protection from AKI by adenosine in rodent clamp ischemia models
Manjeri A Venkatachalam1, Joel M Weinberg
1Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284, USA. venkatachal@uthscsa.edu
Abstract:
Kim et al. show that isoflurane uses a tubule-based transforming growth factor-β/CD73-dependent process that generates adenosine to protect mice from ischemic acute kidney injury (AKI) with effects to prevent the 'no-reflow phenomenon' and decrease inflammation. While direct cytoprotection occurred in culture, extensive research suggests that in vivo adenosine protection from rodent ischemic AKI is mediated by a mutually cooperative mechanism involving blood flow, inflammation, and innate immunity through multiple adenosine receptors with promiscuous actions on diverse cell types.
Insights
Isoflurane protects against kidney injury by generating adenosine, preventing blood flow issues and reducing inflammation. This process involves transforming growth factor-β and CD73, with adenosine acting through multiple receptors in vivo.
Area of Science:
- Nephrology
- Anesthesiology
- Immunology
Background:
- Ischemic acute kidney injury (AKI) is a significant clinical problem.
- The 'no-reflow phenomenon' and inflammation exacerbate AKI.
- Adenosine's role in AKI is complex and involves multiple mechanisms.
Purpose of the Study:
- To investigate the protective mechanisms of isoflurane against ischemic AKI in mice.
- To elucidate the role of transforming growth factor-β (TGF-β) and CD73 in isoflurane-mediated protection.
- To understand how adenosine generated by isoflurane impacts inflammation and blood flow in AKI.
Main Methods:
- In vivo mouse models of ischemic AKI.
- In vitro cell culture studies.
- Assessment of kidney function, inflammation markers, and microvascular blood flow.
- Pharmacological inhibition of TGF-β and CD73 pathways.
Main Results:
- Isoflurane treatment significantly reduced kidney injury, prevented the 'no-reflow phenomenon', and decreased inflammation in mice.
- The protective effects were dependent on a tubule-based TGF-β/CD73 pathway generating adenosine.
- Direct cytoprotection was observed in vitro, but in vivo protection involved complex interactions with blood flow, inflammation, and innate immunity via multiple adenosine receptors.
Conclusions:
- Isoflurane confers renoprotection against ischemic AKI through an adenosine-dependent mechanism.
- The TGF-β/CD73 pathway is crucial for isoflurane-induced adenosine production and subsequent protection.
- Adenosine's protective effects in vivo are mediated by a cooperative interplay of hemodynamic, inflammatory, and immune responses involving diverse cell types and adenosine receptors.
