Kidney Week

Abstract: SA-PO116

Metabolomics Assessment Reveals Amino Acid Depletion in Skeletal Muscle after Ischemic AKI in Mice

Session Information

• AKI: Metabolism and Cell Death
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Li, Amy Shijia, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Amy Shijia Li, MD

• He, Zhibin, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Zhibin He, MS

• Okamura, Kayo, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Kayo Okamura

• Anderson, Colin C., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Colin C. Anderson, PhD

• Haines, Julie, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Julie Haines

• Faubel, Sarah, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Sarah Faubel, MD

Background

Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs, including heart, lungs, and liver, in murine models of AKI. However, AKI-mediated effects on skeletal muscle have not been comprehensively assessed.

Methods

Ischemic AKI was induced in 8-10-week-old male C57BL/6J mice via bilateral pedicle clamping for 25 minutes. Untargeted mass spectrometry metabolomics was performed on gastrocnemius samples at 24-hrs and 72-hrs after AKI with a targeted analysis on energy & redox metabolism. MetaboAnalyst 6.0 was utilized for normalization of the data via autoscaling and statistical analysis.

Results

Univariate ANOVA revealed that 166 of 175 (95%) named metabolites were significantly different among the 5 experimental groups (unmanipulated, 24-hr sham & AKI, 72-hr sham & AKI). The 24-hr AKI group exhibited the most distinct phenotype as demonstrated by principal component analysis (Fig. 1). 30% (50/166) and 16% (27/166) of analytes were significantly different at 24-hrs and 72-hrs after AKI, respectively, compared to sham controls. Hierarchical clustering analysis of the 50 analytes in the 24-hr AKI vs. sham group reveal that 66% (33/50) are reduced (Fig. 2), majority of which are amino acids and their derivatives, which was further supported by pathway analysis.

Conclusion

This is the first study to describe changes of the skeletal muscle metabolome after AKI in a murine model. The metabolome of murine gastrocnemius exhibits significant change after ischemic AKI, particularly at 24 hours. Multiple amino acids and their derivatives are significantly reduced, consistent with the notion that AKI is a hypercatabolic disease, which may lend insight into the mechanistic underpinnings of adverse sequelae associated with AKI in patients.

Fig 1. PCA plot of murine gastrocnemius metabolome at 24-hrs after AKI vs sham.
Fig 2. HCA heat map of top 50 analytes in murine gastrocnemius that are significantly different 24-hrs after AKI vs sham.

Funding

• NIDDK Support