Format

Send to

Choose Destination
Kidney Int. 2019 Mar;95(3):590-610. doi: 10.1016/j.kint.2018.10.020. Epub 2019 Jan 30.

Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice.

Author information

1
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
2
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA; Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
3
Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
4
Department of Pediatrics and Bioengineering, University of Colorado Denver, Aurora, Colorado, USA; Division of Pediatric Cardiology, Department of Pediatrics, University of Colorado Denver, Children's Hospital Colorado, Aurora, Colorado, USA.
5
Department of Pediatrics and Bioengineering, University of Colorado Denver, Aurora, Colorado, USA.
6
Division of Pediatric Cardiology, Department of Pediatrics, University of Colorado Denver, Children's Hospital Colorado, Aurora, Colorado, USA.
7
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
8
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA; Denver VA Medical Center, Division of Nephrology, Department of Medicine, Denver, Colorado, USA.
9
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
10
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA; Denver VA Medical Center, Division of Nephrology, Department of Medicine, Denver, Colorado, USA. Electronic address: Sarah.faubel@ucdenver.edu.

Abstract

Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardiac injury, the cardiac metabolome is characterized by inadequate oxidative phosphorylation, increased oxidative stress, and increased alternate energy utilization. We assessed the impact of ischemic AKI on the metabolomics profile in the heart. Ischemic AKI was induced by 22 minutes of renal pedicle clamping, and 124 metabolites were measured in the heart at 4 hours, 24 hours, and 7 days post-procedure. Forty-one percent of measured metabolites were affected, with the most prominent changes observed 24 hours post-AKI. The post-AKI cardiac metabolome was characterized by amino acid depletion, increased oxidative stress, and evidence of alternative energy production, including a shift to anaerobic forms of energy production. These metabolomic effects were associated with significant cardiac ATP depletion and with echocardiographic evidence of diastolic dysfunction. In the kidney, metabolomics analysis revealed shifts suggestive of energy depletion and oxidative stress, which were reflected systemically in the plasma. This is the first study to examine the cardiac metabolome after AKI, and demonstrates that effects of ischemic AKI on the heart are akin to the effects of direct ischemic cardiac injury.

KEYWORDS:

acute kidney injury; cardiorenal syndrome; metabolomics; organ crosstalk

PMID:
30709662
PMCID:
PMC6564679
[Available on 2020-03-01]
DOI:
10.1016/j.kint.2018.10.020

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center