N-Glycan MALDI MSI Differentiates Kidney Glomerular Disease Phenotypes

Area of Science:

• Glycomics
• Renal Pathology
• Mass Spectrometry Imaging

Background:

• Lupus nephritis (LN) and diabetic nephropathy (DN) are major causes of kidney failure with overlapping glomerular injury patterns.
• Histopathology offers limited insight into the molecular changes driving these kidney diseases.

Purpose of the Study:

• To define the spatial N-glycan landscape in human kidney biopsies from healthy controls, DN, and LN patients using MALDI-MSI.
• To investigate how N-glycan distribution differs across disease states and at the glomerular level.

Main Methods:

• Applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to analyze N-glycans in whole kidney biopsies and individual glomeruli.
• Utilized mixed-effect modeling and MALDI-immunohistochemistry (MALDI-IHC) for detailed analysis.

Main Results:

• Identified distinct spatial N-glycan distributions specific to healthy kidneys, DN, and LN.
• Glomerulus-resolved analysis revealed disease-specific molecular phenotypes masked at the whole-biopsy level.
• Even histologically normal glomeruli showed distinct N-glycan signatures across disease states, indicating early molecular remodeling.

Conclusions:

• Glomerular N-glycan architecture is a key factor in glycomic differences observed in kidney diseases.
• Spatial N-glycomics is a promising translational tool for identifying disease-specific molecular signatures in intact kidney tissues.