Journal article
Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice
Kidney international, Vol.95(3), pp.590-610
03/2019
DOI: 10.1016/j.kint.2018.10.020
PMCID: PMC6564679
PMID: 30709662
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.
Details
- Title: Subtitle
- Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice
- Creators
- Benjamin M. Fox - University of Colorado DenverHyo-Wook Gil - University of Colorado DenverLara Kirkbride-Romeo - University of Colorado DenverRushita A. Bagchi - University of Colorado Anschutz Medical CampusSara A. Wennersten - University of Colorado Anschutz Medical CampusKorey R. Haefner - University of Colorado DenverNataliya I. Skrypnyk - University of Colorado DenverCarolyn N. Brown - University of Colorado DenverDanielle E. Soranno - University of Colorado DenverKatja M. Gist - Children's Hospital ColoradoBenjamin R. Griffin - University of Colorado DenverAnna Jovanovich - University of Colorado DenverJulie A. Reisz - University of Colorado DenverMatthew J. Wither - University of Colorado DenverAngelo D'Alessandro - University of Colorado DenverCharles L. Edelstein - Denver VA Medical CenterNathan Clendenen - University of Colorado Anschutz Medical CampusTimothy A. McKinsey - University of Colorado Anschutz Medical CampusChristopher Altmann - University of Colorado DenverSarah Faubel - Denver VA Medical Center
- Resource Type
- Journal article
- Publication Details
- Kidney international, Vol.95(3), pp.590-610
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.kint.2018.10.020
- PMID
- 30709662
- PMCID
- PMC6564679
- ISSN
- 0085-2538
- eISSN
- 1523-1755
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: HL116848, HL127240, AG043822; DOI: 10.13039/501100000024, name: Canadian Institutes of Health Research, award: FRN-216927; DOI: 10.13039/100000968, name: American Heart Association, award: 16SFRN31400013
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359845202771
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