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Kidney Week

Abstract: PO2495

Localization of Metabolites in Tubulointerstitial Disease

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Pamreddy, Annapurna, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Zhang, Guanshi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Velickovic, Dusan, William R Wiley Environmental Molecular Sciences Laboratory, Richland, Washington, United States
  • Venkatachalam, Manjeri A., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Alexandrov, Theodore, European Molecular Biology Laboratory, Heidelberg, Baden-Württemberg, Germany
  • Anderton, Christopher R., William R Wiley Environmental Molecular Sciences Laboratory, Richland, Washington, United States
  • Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Group or Team Name

  • CRPM and KPMP
Background

Tubulointerstitial (TI) disease plays a critical role in the outcome of patients with chronic kidney disease, however the basic biochemical pathways that generate the TI damage remain unclear. The application of metabolomics in chronic kidney disease (CKD) studies provide researchers the opportunity to gain new insights into metabolic profiling and pathophysiological mechanisms. Mass spectrometry imaging (MSI) is a promising approach that has the potential in reveal spatially-resolved metabolic information within kidney tissue across different disease states.

Methods

In the current study, we employed a high-resolution matrix-assisted laser desorption/ionization (MALDI)-MSI approach to characterize small molecules in human kidney biopsy core samples (n=6) were received from KPMP recruitment sites (CCF, JOS, UTSW, CLU, JHMI, YLE, UPMC, BMC, CIN-HRT and UMI-CBR). The data output was uploaded to METASPACE for molecular annotation, and SCiLS Lab, Metaboanalyst, and Cytoscape were utilized for data processing and statistical analyses.

Results

In total, 600 small metabolites (m/z 80-1000) were annotated by METASPACE using the human metabolome database (20% FDR) in human kidney biopsy core sections. MALDI-MSI of human kidney biopsy core sections exhibited different spatial distributions of intermediates in the tricarboxylic acid cycle, glutamate-glutamine cycle, malate-aspartate shuttle, and phospholipid metabolism, simultaneously. Specifically, D-4’-phosphopantothenate (m/z 298.0697) was identified as a new glomerular-enriched marker in normal glomeruli but was also present in atrophic tubule. The glycolytic metabolite glucose-6-phosphate (m/z 259.0224) was enriched in normal tubules and not over expressed in atrophic tubule.

Conclusion

MALDI MSI is potentially an effective tool for small molecule in situ analysis of human kidney tissue. MALDI-MSI technology, coupled with METASPACE, shed new light on omics data integration studies. In summary, from an individual patient with CKD, we found spatial restrictions of metabolites to normal tubule and potentially with atrophic tubule.

Funding

  • NIDDK Support