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Metabolomic assessment reveals depletion of amino acids and energy metabolites in skeletal muscle after ischemic acute kidney injury in mice
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  • Published: 13 February 2026

Metabolomic assessment reveals depletion of amino acids and energy metabolites in skeletal muscle after ischemic acute kidney injury in mice

  • Amy S. Li1 na1,
  • Peter R. Baker II2 na1,
  • Samel Park1,
  • Isadore Budnick3,
  • Zhibin He1,
  • Kayo Okamura1,
  • Hyo-wook Gil4,
  • Makoto Miyazaki1,
  • Colin C. Anderson5,
  • Julie A. Reisz5 &
  • …
  • Sarah Faubel1 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Biomarkers
  • Medical research
  • Nephrology
  • Physiology

Abstract

Acute kidney injury (AKI) is a systemic catabolic condition that affects multiple organs. Clinically, AKI has been associated with muscle wasting, weakness, and delayed functional recovery. The underlying biochemical mechanisms driving these changes are not well understood. Ischemic AKI was induced in 8-10-week-old male C57BL/6 mice. Untargeted metabolomics on gastrocnemius samples were performed via ultra-high performance liquid chromatography-mass spectrometry at 24 h and 72 h after AKI. Of the 175 annotated analytes identified, 72 were significantly affected at 24 h with the majority of these metabolites being depleted in AKI compared to controls. Key depleted metabolites included multiple amino acids, glutathione and its precursors, and other energy-related substrates. Integration with our previously published metabolomics data in the kidney, liver, heart, and plasma highlights shared metabolic pathways across these organs, particularly reflected in arginine metabolism and the urea cycle, alanine/aspartate/glutamate metabolism, and glutathione/redox balance. This is the first study to characterize the metabolic profile of skeletal muscle after ischemic AKI in a murine model. Our data deepen the understanding of AKI as a systemic metabolic disease, underscoring the need to further understand the effects of AKI on skeletal muscle and opening potential avenues for therapeutic strategies to improve outcomes after AKI.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by 5R01HL157973 (SF). The University of Colorado School of Medicine Metabolomic Core is supported in part by the University of Colorado Cancer Center award from the National Cancer Institute P30CA046934. ASL was funded by the National Institutes of Health grant 5T32DK007135-46. IB is funded by the National Institutes of Health grant 2T32HL007085-51.

Author information

Author notes

  1. Amy S. Li and Peter R. Baker II contributed equally to this work.

Authors and Affiliations

  1. Division of Renal Diseases and Hypertension, Department of Internal Medicine, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Box C281, Aurora, CO, 80045, USA

    Amy S. Li, Samel Park, Zhibin He, Kayo Okamura, Makoto Miyazaki & Sarah Faubel

  2. Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, 13123 East 16th Avenue, Box 300, Aurora, CO, 80045, USA

    Peter R. Baker II

  3. Division of Pulmonary Sciences and Critical Care Medicine, Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Isadore Budnick

  4. Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea

    Hyo-wook Gil

  5. Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO, 80045, USA

    Colin C. Anderson & Julie A. Reisz

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Contributions

A.S.L., P.R.B., and S.F. conceptualized the study. A.S.L., K.O., Z.H., M.M., C.C.A., and H.G. performed experiments and acquired data. A.S.L., P.R.B., I.B., S.P., C.C.A., J.A.R., S.F. contributed to data analysis and interpretation. A.S.L., P.R.B., S.P., I.B., and S.F. drafted and edited the final version of the manuscript. All authors contributed to reviewing the manuscript. A.S.L. and P.R.B. contributed equally.

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Correspondence to Sarah Faubel.

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Li, A.S., Baker, P.R., Park, S. et al. Metabolomic assessment reveals depletion of amino acids and energy metabolites in skeletal muscle after ischemic acute kidney injury in mice. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37424-y

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  • Received: 11 August 2025

  • Accepted: 22 January 2026

  • Published: 13 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-37424-y

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