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Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research
Published on: November 3, 2023
Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection
Holger Scholz1, Felix J Boivin1,2, Kai M Schmidt-Ott1,2
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Abstract:
Kidney damage varies according to the primary insult. Different aetiologies of acute kidney injury (AKI), including kidney ischaemia, exposure to nephrotoxins, dehydration or sepsis, are associated with characteristic patterns of damage and changes in gene expression, which can provide insight into the mechanisms that lead to persistent structural and functional damage. Early morphological alterations are driven by a delicate balance between energy demand and oxygen supply, which varies considerably in different regions of the kidney. The functional heterogeneity of the various nephron segments is reflected in their use of different metabolic pathways. AKI is often linked to defects in kidney oxygen supply, and some nephron segments might not be able to shift to anaerobic metabolism under low oxygen conditions or might have remarkably low basal oxygen levels, which enhances their vulnerability to damage. Here, we discuss why specific kidney regions are at particular risk of injury and how this information might help to delineate novel routes for mitigating injury and avoiding permanent damage. We suggest that the physiological heterogeneity of the kidney should be taken into account when exploring novel renoprotective strategies, such as improvement of kidney tissue oxygenation, stimulation of hypoxia signalling pathways and modulation of cellular energy metabolism.
Insights
Different kidney regions exhibit varying vulnerability to acute kidney injury (AKI) due to oxygen supply and metabolic differences. Understanding this physiological heterogeneity can guide novel strategies to prevent kidney damage.
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- Acute kidney injury (AKI) presents diverse damage patterns based on the initial cause (e.g., ischemia, toxins, sepsis).
- Kidney structure exhibits regional functional and metabolic heterogeneity, influencing susceptibility to injury.
- Oxygen supply-demand balance and metabolic pathway utilization vary across nephron segments, impacting vulnerability.
Purpose of the Study:
- To elucidate why specific kidney regions are particularly susceptible to acute kidney injury.
- To explore how regional kidney vulnerability can inform strategies for mitigating damage and preventing chronic kidney disease.
Main Methods:
- Review of existing literature on kidney physiology, AKI mechanisms, and gene expression patterns.
- Analysis of regional differences in oxygen metabolism and energy demand within the kidney.
- Discussion of potential renoprotective strategies based on physiological heterogeneity.
Main Results:
- Specific kidney regions are predisposed to AKI due to inherent differences in oxygen levels and metabolic adaptability.
- Some nephron segments struggle to switch to anaerobic metabolism during low oxygen conditions, increasing damage risk.
- Gene expression changes correlate with specific injury patterns in different kidney regions.
Conclusions:
- Kidney injury susceptibility is linked to regional physiological and metabolic characteristics.
- Novel renoprotective strategies should consider the kidney's inherent heterogeneity.
- Targeting oxygenation, hypoxia signaling, and cellular metabolism may prevent kidney damage.
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