Exploration of renal space: navigating injury and repair through spatial omics

Abstract

This thesis explores how cellular metabolism shapes kidney injury and repair, using advanced spatial metabolomics to map metabolic processes directly within the tissue. By applying mass spectrometry imaging and new computational strategies, it reveals that metabolism is a crucial player in both acute and chronic settings of kidney injury. A central finding is that early in diabetes, the proximal tubule S3 segment undergoes distinct membrane lipid remodeling. This shift reduces membrane stability and makes this segment especially vulnerable, identifying PT-S3 as a key early site of diabetes-induced metabolic alterations. Methodological advances are another major contribution. This thesis establishes practical protocols for spatial dynamic metabolomics, enabling researchers to visualize not only which metabolites are present, but how actively they are produced. Applied to renal cell carcinoma, this approach captured the Warburg effect in single cells in situ. Finally, the work reveals that after acute kidney injury, metabolic disturbances extends in patches of injury. Even seemingly healthy epithelial cells become metabolically impaired when located within an injured niche, marked by disrupted succinate and fatty-acid metabolism. These findings highlight the importance of metabolic resuscitation of the injury microenvironment.