Kidney Week

Abstract: FR-OR90

Purine and Pyrimidine Metabolism Decrease in the First Hour of Warm Ischemia in Kidney Tissue: Spatiotemporal Detection by Mass Spectrometry Imaging

Session Information

• Pathology and Lab Medicine Advances
  October 25, 2024 | Location: Room 2, Convention Center
  Abstract Time: 05:50 PM - 06:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Peutz-Kootstra, Carine, Gelre Ziekenhuizen, Apeldoorn, Gelderland, Netherlands

Carine Peutz-Kootstra, MD, PhD

• Balluff, Benjamin, Maastricht Multimodal Molecular Imaging Institute - M4i, Maastricht, Netherlands

Benjamin Balluff, PhD

• Van smaalen, Tim C., Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Tim C. Van smaalen, MD

• Snoeijs, Maarten G., Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Maarten G. Snoeijs, MD, PhD

• Heeren, Ron M.A., Maastricht Multimodal Molecular Imaging Institute - M4i, Maastricht, Netherlands

Ron M.A. Heeren, PhD

• de Hoogt, Patrick A., Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Patrick A. de Hoogt, MD

Background

Warm ischemia is an important cause of acute kidney injury. Mass Spectrometry Imaging (MSI) can visualize metabolic alterations in renal tissue biopsies.

Methods

In order to identify alternating metabolites during the first hour of warm ischemia, kidney samples from five pigs were measured by high-mass resolution matrix-assisted laser desorption/ionization (MALDI) MSI after 0, 20, 40, and 60 minutes of warm ischemia.

Results

Contrasting the metabolites’ distributions with the kidney’s microanatomy revealed a cortical decrease in abundance of 56 metabolite signals between 0 and 40 minutes, and of 89 signals between 0 and 60 minutes. Tandem MS identified eleven metabolites of which ten belong to the purine and pyrimidine pathways. There was an attenuated loss of adenosine tri- and diphosphate (ATP and ADP) in medullary rays. Phosphatidylserine 18:0_18:1 was decreased in the cortex, but only in the first 40 minutes of ischemia.

Conclusion

In conclusion, MSI discerns metabolites with differential spatial and temporal expression during warm ischemic injury in renal tissue. Rapid cortical, but slow medullary loss of ATP and ADP metabolism discriminates energy homeostasis pathways affected by acute kidney injury.

Figure 1. Different spatiotemporal expression patterns of metabolites identified by MSI and MS/MS. Heat map analysis (panel A) of the eleven identified compounds shows differences in spatial expression pattern over time. Panell B shows a different spatial expression for ATP (yellow) and AMP (green) at 0 minutes in cortex and medulla, with a decrease after 20, 40 and 60 minutes of warm ischemia. Higher magnification (panel C) shows that expression of ATP remains in the medullary rays, while AMP expression is still diffusely present in the cortex after 20 minutes of warm ischemia.