ArticleJournal of the American Society of Nephrology : JASN2014
Renal cortical pyruvate depletion during AKI.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
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- Explainable machine learning using urinary metabolomics to predict pediatric sepsis-associated acute kidney injury: a two-center prospective observational study.Renal failure · 2026Observational
- Haikun Shenxi Capsule Ameliorates Renal Fibrosis by Modulating Gut Microbiota and Metabolism.Current medical science · 2026Article
- Structural decomposition enables multi-omics dissection of common and organ-specific aging.Science China. Life sciences · 2026Article
- Dietary methionine deprivation enhances renal resilience against ischemia-reperfusion injury in mice through modulation of glucose oxidation.Communications biology · 2025Article
- The new insights of lactate in various kidney diseases.Expert reviews in molecular medicine · 2025Review
- Metabolite-enhanced normothermic machine perfusion improves kidney transplant viability.JCI insight · 2025Article
- Lactate and Lactylation in AKI-to-CKD: Epigenetic Regulation and Therapeutic Opportunities.Cell proliferation · 2025Review
- Strengthening monocarboxylate transporters by adiponectin receptor agonist ameliorates diabetic peripheral neuropathy.Cell communication and signaling : CCS · 2025Article
- Glycerol-3-phosphate contributes to the increase in FGF23 production in chronic kidney disease.American journal of physiology. Renal physiology · 2025Article
- Overexpression of GDF15 protects kidneys from ischemia reperfusion injury and affects circular RNA expression.Frontiers in cell and developmental biology · 2025Article
- AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis.Molecular medicine (Cambridge, Mass.) · 2024Article
- The key role of altered tubule cell lipid metabolism in kidney disease development.Kidney international · 2024Review
- Review on Kidney-Liver Crosstalk: Pathophysiology of Their Disorders.Cell journal · 2024Article
- Noninvasive measurement ofCommunications medicine · 2023Article
- Exploratory metabolomic analysis based on UHPLC-Q-TOF-MS/MS to study hypoxia-reoxygenation energy metabolic alterations in HK-2 cells.Renal failure · 2023Article
- Transcriptional regulation of proximal tubular metabolism in acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2023Review
- The metabolic pathway regulation in kidney injury and repair.Frontiers in physiology · 2023Review
- Energy metabolic reprogramming regulates programmed cell death of renal tubular epithelial cells and might serve as a new therapeutic target for acute kidney injury.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15-60 minutes; 0-18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury.
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