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Renal cortical pyruvate depletion during AKI
Richard A Zager1, Ali C M Johnson2, Kirsten Becker2
1Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington dzager@fhcrc.org.
Journal of the American Society of Nephrology : JASN
|January 4, 2014
Summary
Acute kidney injury (AKI) causes significant pyruvate depletion in the kidneys, impacting energy metabolism. Pyruvate therapy shows promise in mitigating AKI severity and inflammation.
Area of Science:
- Biochemistry
- Renal Physiology
- Metabolic pathways
Background:
- Pyruvate is central to cellular energy metabolism.
- Pyruvate also possesses antioxidant and anti-inflammatory properties.
- The role and metabolic fate of pyruvate during acute kidney injury (AKI) are not well understood.
Purpose of the Study:
- To investigate the changes in renal cortical pyruvate levels during AKI.
- To identify the key metabolic factors influencing pyruvate levels in AKI.
- To evaluate the therapeutic potential of pyruvate in AKI.
Main Methods:
- Mice models of unilateral ischemia-reperfusion and glycerol-induced AKI were used.
- Renal cortical pyruvate, lactate, glucose, H2O2, and enzyme levels (PDH) were measured.
- Gene expression of inflammatory and cytoprotective markers was analyzed.
- Effects of pyruvate administration on AKI severity and metabolic parameters were assessed.
Main Results:
- Both ischemia-reperfusion and glycerol-induced AKI led to persistent renal cortical pyruvate depletion.
- Pyruvate depletion correlated with increased gluconeogenesis and decreased pyruvate dehydrogenase activity.
- Pyruvate therapy attenuated AKI severity, reduced inflammation, and improved ATP levels.
- Paradoxically, pyruvate administration increased cortical H2O2 levels.
Conclusions:
- AKI causes profound and sustained depletion of renal cortical pyruvate.
- This pyruvate depletion may contribute to AKI pathogenesis.
- Pyruvate therapy demonstrates renoprotective effects in AKI models.
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