N-Glycan MALDI MSI Differentiates Kidney Glomerular Disease Phenotypes

Area of Science:

• Glycomics
• Mass Spectrometry Imaging
• Renal Pathology

Background:

• Lupus nephritis (LN) and diabetic nephropathy (DN) are major causes of kidney failure.
• Histopathology offers limited insight into molecular changes in kidney diseases.
• Understanding molecular remodeling is crucial for diagnosing and treating kidney diseases.

Purpose of the Study:

• To define the spatial N-glycan landscape in human kidney biopsies from healthy controls, DN, and LN patients.
• To investigate how N-glycan distribution differs across disease states and at the glomerular level.
• To establish spatial N-glycomics as a tool for identifying disease-specific molecular signatures.

Main Methods:

• Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was applied to whole kidney biopsies and glomeruli.
• N-glycan profiles were analyzed in healthy controls, diabetic nephropathy, and lupus nephritis.
• Mixed-effect modeling and MALDI-immunohistochemistry (MALDI-IHC) were used for analysis.

Main Results:

• Distinct N-glycan spatial distributions were observed in DN and LN compared to healthy kidneys.
• 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 significantly drives glycomic differences in kidney diseases.
• Spatial N-glycomics provides a translational approach to define disease-specific molecular signatures in intact renal tissues.
• This technique enhances the understanding of molecular remodeling in kidney failure.