Abstract: SA-PO122
Metabolic Alterations in Organs and Biofluids following Unilateral Ischemia-Reperfusion Kidney Injury in Pigs
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
- Hahn, Oliver, Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Chrysopoulou, Maria, Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Jaegers, Johannes, Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Laustsen, Christoffer, MR Research Centre, Aarhus University, Aarhus, Denmark
- Rinschen, Markus M., Department of Biomedicine, Aarhus University, Aarhus, Denmark
Group or Team Name
- Kidney Omics Group.
Background
The kidneys play a crucial role in eliminating metabolic waste products and regulating various metabolites. However, metabolic alterations in renal injury sometimes remain un-interpretable, since multiple organ systems may be affected.
Methods
We employed stable isotopes 13-Carbon glucose and 15-Nitrogen ammonium chloride to track metabolites across pig organs subjected to unilateral ischemia-reperfusion kidney injury for 2 hours and either one or four days of recovery. Utilizing ultra-high-pressure liquid chromatography-triple quadrupole tandem mass spectrometry, we accurately measured both labeled and unlabeled metabolites, enabling precise quantification of metabolite fluxes and fates. Additionally, we assessed changes in the proteome to correlate with metabolite fluxes.
Results
Using functional MRI, we accurately phenotyped the pigs and observed a significant decrease in the single kidney GFR of the injured kidney. Ammonia flux in the kidney medulla increased after 1 and 4 days of recovery in both the ipsilateral and contralateral kidneys compared to the kidneys of the control pigs. In contrast, ammonia flux remained unchanged in other organs, including the liver, heart, muscle, and brain. Additionally, measurements of metabolites from the citric acid cycle, urea cycle, and glycolysis indicated a strong metabolic rewiring to ischemia reperfusion injury. Proteome changes correlated with the observed findings, but subtle changes were also observed in the non-injured, contralateral kidney.
Conclusion
The metabolic epicenter of acute injury is the injured kidney, but distinct metabolic alterations are observed in the other kidney and, partly, other organs. These metabolic alterations are sequelae of renal injury and provide a first window into initial metabolic mechanisms conveying cardiovascular risk in renal injury.
Funding
- Commercial Support – Novo Nordisk foundation