Abstract: TH-PO105
Mass Spectrometry Imaging Reveals Metabolic Switch to Glycolysis in Proximal Tubules During AKI
Session Information
- AKI: Mechanisms - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Zhang, Guanshi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Tamayo, Ian M., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Liu, Li, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Velickovic, Dusan, Pacific Northwest National Laboratory, Richland, Washington, United States
- Gorman, Brittney L., Pacific Northwest National Laboratory, Richland, Washington, United States
- Anderton, Christopher R., Pacific Northwest National Laboratory, Richland, Washington, United States
- Alexandrov, Theodore, European Molecular Biology Laboratory, Heidelberg, Germany
- Venkatachalam, Manjeri A., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Reeves, William Brian, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Group or Team Name
- For the KPMP Consortium.
Background
Aberrant glucose metabolism has been reported in the pathogenesis of acute kidney injury (AKI). In vitro studies of proximal tubular cells showed damaged cells that were unable to fully recover underwent a metabolic switch to glycolysis during the AKI to CKD transition. Additionally, In vivo data of AKI murine models also demonstrated upregulated expression of rate-limiting enzymes of glycolysis in mice with AKI. However, changes in energy metabolism under AKI in human patients remain an enigma. We performed a comprehensive analysis of metabolites in proximal tubules of kidney biopsies from AKI patients vs healthy reference tissues (HRT).
Methods
A matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) platform was employed to characterize the metabolic profile in kidney biopsies from AKI patients (n = 6) and HRT (n = 6) in situ (spatial resolution: 20 μm). SCiLS Lab was used for raw data processing. METASPACE was applied for metabolite annotations at 20% FDR. Univariate (t-test) and multivariate (e.g., PCA and PLS-DA) analyses were performed to compare metabolic profiles in kidney biopsies between AKI and HRT.
Results
In total, 1797 m/z’s were annotated as different metabolite species in human kidney biopsies. Specifically, seven metabolites from the tricarboxylic acid cycle and 10 intermediates from glycolysis were measured. Multivariate analyses showed clearly separated clusters between AKI and HRT biopsies, suggesting aberrant metabolic changes in AKI kidneys. Univariate analysis revealed that 361 metabolites were significantly different in proximal tubules of AKI compared to HRT. Particularly, several glycolytic intermediates including lactic acid (P = 0.0251), 2-phosphoglycerate (P=0.0152), and fructose-6-phosphate (P=0.0013) were found to accumulate in proximal tubules of AKI renal biopsies, suggesting the potential role of metabolic switch to glycolysis in the kidney with AKI.
Conclusion
These findings demonstrate an accumulation of glycolytic intermediates in proximal tubules of AKI kidney biopsies which may play an important role in the pathogenesis of AKI. Our human kidney biopsy data reveal a potential metabolic switch to glycolysis in damaged proximal tubular cells during the AKI to CKD transition.
Funding
- NIDDK Support