Kidney Week

Abstract: FR-PO0363

Glutamine Treatment Improves Cardiac Energy Metabolism in Mice with AKI

Session Information

• AKI: Mechanisms - Metabolism and Repair
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Bevers, Shaun, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Shaun Bevers, PhD

• Baker, Peter R., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Peter R. Baker, MD

• Carniglia, Giada, University of Colorado Anschutz Medical Campus, Aurora, United States

Giada Carniglia, MS, MSc

• Park, Samel, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Samel Park, DrMed

• Elajaili, Hanan B., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Hanan B. Elajaili

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

Kayo Okamura

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

Zhibin He, MS

• Sparagna, Genevieve C., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Genevieve C. Sparagna, PhD

• Budnick, Isadore, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Isadore Budnick, MD

• Nozik, Eva S., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Eva S. Nozik, MD

• Sucharov, Carmen, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Carmen Sucharov, PhD

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

Sarah Faubel, MD

Background

After ischemic AKI in mice, the heart exhibits changes in energy metabolism characterized by ATP depletion, mitochondrial and beta-oxidative dysfunction, and amino acid depletion. The amino acid glutamine improves cardiac energy profiles in human and murine studies of direct cardiac ischemia (e.g., myocardial infarction, cardiopulmonary bypass). Since there is currently no therapy for AKI-associated cardiac injury (cardiorenal syndrome type 3), we investigated the role of glutamine treatment in cardiac energy production after AKI.

Methods

6 groups of adult, male, C576/J wild type mice were studied: normal (no surgery), sham (surgery without kidney ischemia), and ischemic AKI treated with vehicle or 0.75 mg/kg glutamine 18 hrs prior to surgery for sham or AKI, and then daily. Endpoints were determined at 24 and 72 hours. Ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) was used to assess ATP and metabolites in the plasma and heart. Pathway enrichment analysis was performed using Metaboanalyst 6.0. Cardiac mitochondrial respiration was assessed with high resolution respirometry using the Oroboros oxygraph 2k system. Superoxide levels were assessed via electron paramagnetic resonance (EPR). Plasma metabolites were assessed by UCPLC-MS in 89 patients with AKI and 26 healthy controls.

Results

After AKI, the following effects were observed in the heart with glutamine treatment: 1) ATP was significantly increased, 2) purine metabolism was significantly affected (Figure 1), 3) superoxide levels were significantly reduced, and 4) mitochondrial respiration was improved. In the plasma, patients and mice (without glutamine treatment) with AKI had similar perturbations in purine metabolites.

Conclusion

Glutamine administration may be a viable treatment strategy in patients with AKI to improve cardiorenal syndrome type 3.

Figure 1. In normal, sham, and AKI mice, glutamine treatment significantly affects cardiac purine metabolism (SMPDB: small molecule pathway database) (A) and significantly affects cardiac levels of purine and related metabolites, including ATP (B).

Funding

• Other NIH Support