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

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.