Abstract: FR-PO0329
Spatial Metabolomics Reveal Distinct Metabolic Signatures in Atrophic Tubules of Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 1
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Maity, Soumya, 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
- Zhang, Shiqi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Dandan, Jad Michael, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Bjornstad, Petter, University of Washington, Seattle, Washington, United States
- Sharma, Shoba, SygnaMap, Inc. San Antonio, San Antonio, Texas, United States
- Hodgin, Jeffrey B., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Jain, Sanjay, Washington University in St Louis School of Medicine, St. Louis, Missouri, 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 Kidney Precision Medicine Project (KPMP).
Background
Chronic kidney disease (CKD) is a global health challenge marked by the gradual and often silent decline in kidney function. Tubular atrophy, a type of tissue damage in the kidney's tubules, is a strong indicator of disease progression and loss of renal function in CKD. However, the metabolic alterations associated with this pathological feature remain poorly understood. In this study, we aimed to characterize metabolic reprogramming in atrophic tubules of patients with diabetic kidney disease (DKD).
Methods
We performed spatial metabolomics via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to map and compare the metabolic profiles of atrophic versus non-atrophic tubules in kidney biopsies from KPMP participants with type 2 diabetes (n=10). Regions of interest were annotated using QuPath on PAS-stained serial sections adjacent to MALDI-MSI tissue, with 30 atrophic and 30 non-atrophic tubule regions per samples. These annotations were aligned with MALDI-MSI data to extract region-specific metabolite signatures. Unbiased statistical analysis was performed using MetaboAnalyst 6.0.
Results
By integrating high-resolution histological data with spatial metabolomics, we identified distinct metabolic signatures distinguishing atrophic from non-atrophic tubules. In atrophic regions, 190 metabolites were significantly downregulated and 88 were upregulated. Notably, the accumulation of glucose, lactate, and citrate, alongside the depletion of free fatty acids, suggests a metabolic shift toward glycolysis and impaired mitochondrial function. Bioenergetic dysregulation was further supported by a decreased AMP/ATP ratio in atrophic tubules. Pathway enrichment analysis revealed prominent alterations in amino sugar metabolism, aspartate metabolism, purine metabolism, glycerolipid metabolism, glutamate metabolism, glutathione metabolism, the pentose phosphate pathway, and the urea cycle.
Conclusion
This study provides new insights into the metabolic reprogramming associated with tubular atrophy in DKD. The identified metabolic alterations may serve as potential biomarkers or therapeutic targets to monitor and mitigate CKD progression.
Funding
- NIDDK Support