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Kidney Week

Abstract: FR-PO123

Metabolomics in the Lung After Ischemic AKI Reveals Increased Oxidative Stress, Altered Energy Production, and Energy Depletion

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Ambruso, Sophia L., University of Colorado Denver, Denver, Colorado, United States
  • Fox, Benjamin, CU Anschutz Medical Campus, Goleta, California, United States
  • Gil, Hyo-Wook, Soonchunhyang University Cheonan Hospital, Cheonan, Korea (the Republic of)
  • Bagchi, Rushita A., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Baker, Peter R., University of Colorado , Aurora, Colorado, United States
  • Faubel, Sarah, University of Colorado Denver, Denver, Colorado, United States

Acute kidney injury (AKI) is a systemic disease with deleterious effects on distant organs, including the lung. Lung function is dependent upon redox homeostasis and ATP generation through oxidative phosphorylation. Acute lung injury (ALI) after AKI is characterized by acute inflammation and neutrophil accumulation. Metabolically, ALI shows increased oxidative stress, energy depletion, and altered energy production. We sought to determine the effect of AKI on lung metabolism.


Normal mice and mice after sham (surgery alone) or surgery for ischemic AKI (22 minutes of bilateral renal pedicle clamping) were studied at 4-hours, 24-hours or 7 days post procedure. Lung metabolomics was performed via ultra high-pressure liquid chromatography coupled to online mass spectrometry (UHPLC-MS). Untargeted UHPLC-MS-based metabolomics analysis provided the measurement of 132 annotated metabolites in the lung. Commercially available reagents (Abcam; ab833355) were used to measure lung ATP.


AKI had a significant effect on the lung metabolome at 4- and 24-hours post-procedure. There was evidence of 1) increased catabolism characterized by decreased amino acids and their metabolites (ie. Leucine/Isoleucine, Phenylalanine, S-Adenosyl-L-Methionine at 4 hours and lysine, D-O-phosphoserine, L-adrenaline, L-carnitine and O-propanoylcarnitine at 24 hours), 2) increased oxidative stress and dysregulated redox system via decreased levels of glutathione, thioredoxin disulfide, nicotinamide and adenosine, and 3) use of alternative energy sources characterized by decreased intermediates in glycolysis (ie. lactate and D-glucose) and the pentose phosphate pathway (ie. D-Ribitol-5-Phosphate and D-Ribose). Lung ATP levels were reduced in the lung after AKI compared to sham and control at 4 hours [control CI 2.5-6.8 (p <0.0001), sham CI 2.3-6.0 (p<0.0001)] and 24 hours [control CI 0.8-5.6 (p=0.003), sham CI 0.5-4.9 (p=0.007)].


This is the first study to examine the metabolome and ATP levels post-ischemic AKI in the lung. Our findings show depleted ATP levels and evidence of increased oxidative stress, energy depletion and use of alternative energy production. Further metabolomic profiling in the lung post-AKI is needed to identify pathways for future clinical interventions.


  • Other NIH Support