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Cited by 64Acute Kidney Injury ResearchChronic Kidney Disease and DiabetesRenal Diseases and Glomerulopathies

Tubular Cell Glucose Metabolism Shift During Acute and Chronic Injuries

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Faivre, Anna, Verissimo, Thomas, Auwerx, Hannah, Legouis, David, de Seigneux, Sophie·2021·Frontiers in Medicine
DOI 10.3389/fmed.2021.742072PMC PMC8585753
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Abstract

Acute and chronic kidney disease are responsible for large healthcare costs worldwide. During injury, kidney metabolism undergoes profound modifications in order to adapt to oxygen and nutrient shortage. Several studies highlighted recently the importance of these metabolic adaptations in acute as well as in chronic phases of renal disease, with a potential deleterious effect on fibrosis progression. Until recently, glucose metabolism in the kidney has been poorly studied, even though the kidney has the capacity to use and produce glucose, depending on the segment of the nephron. During physiology, renal proximal tubular cells use the beta-oxidation of fatty acid to generate large amounts of energy, and can also produce glucose through gluconeogenesis. In acute kidney injury, proximal tubular cells metabolism undergo a metabolic shift, shifting away from beta-oxidation of fatty acids and gluconeogenesis toward glycolysis. In chronic kidney disease, the loss of fatty acid oxidation is also well-described, and data about glucose metabolism are emerging. We here review the modifications of proximal tubular cells glucose metabolism during acute and chronic kidney disease and their potential consequences, as well as the potential therapeutic implications.

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  • There is some evidence that the shift to glycolysis in the kidney may be protective in times of stress but may contribute to the development of chronic kidney disease.

    “There is some evidence that, while this may be a protective response of the kidney in times of stress, this process may contribute to the development of chronic kidney disease (CKD) [28].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [28]

  • Under normal conditions, proximal tubular cells participate in gluconeogenesis and generate ATP via fatty acid oxidation; when there is poor perfusion and decreased oxygen supply, intracellular metabolic pathways shift to glycolysis.

    “Under normal conditions, proximal tubular cells participate in gluconeogenesis and generate ATP via fatty acid oxidation. When there is poor perfusion and decreased oxygen supply, intracellular metabolic pathways shift to glycolysis, an anaerobic but inefficient method of ATP generation.”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [28]

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References 137 · Cited by 64

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Authors
Faivre, A., Verissimo, T., Auwerx, H., Legouis, D., & de Seigneux, S.
Affiliations
University of Geneva (CH)
ORCID
Venue
Frontiers in Medicine
Publisher
Frontiers Media SA
Published
2021-10-29
Volume
8
Pages
742072-742072
ISSN
2296-858X (ISSN-L)
DOI
10.3389/fmed.2021.742072
PMC
PMC8585753
OpenAlex
W3209564044
Cited by
64
References
137
Citations by year
2026: 10 · 2025: 7 · 2024: 24 · 2023: 10 · 2022: 13
FWCI
1.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNSF PP00P3-187186/1)
  • Swiss National Centre of Competence in Research Kidney Control of Homeostasis
  • Fondation Centre de Recherches Médicales Carlos et Elsie de Reuter
  • Sir Jules Thorn Charitable Trust
Topics
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Keywords
acute kidney injury, chronic kidney disease, proximal tubular epithelial cells, metabolic switch, glycolysis, gluconeogenesis, fatty acid beta-oxidation, renal fibrosis, therapeutic target

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