Electron Microscopy in Renal Biopsy Interpretation: When and Why It Still Matters.

Electron microscopy (EM) remains an indispensable tool in renal pathology, providing ultrastructural details that complement light microscopy (LM) and immunofluorescence (IF) in the diagnosis of glomerular diseases. This review outlines the diagnostic role of EM across major categories of glomerular pathology, emphasizing its value in confirming and refining histopathological diagnoses. In membranous nephropathy, EM visualizes subepithelial electron-dense deposits and tracks disease progression through glomerular basement membrane (GBM) remodeling. In immune complex-mediated glomerulonephritides, such as IgA nephropathy and lupus nephritis, EM localizes deposits to mesangial, subendothelial, or subepithelial regions, facilitating accurate classification. For C3 glomerulopathies, EM distinguishes dense deposit disease from C3 glomerulonephritis by revealing unique ribbon-like intramembranous densities. In hereditary nephritides like Alport syndrome and thin basement membrane nephropathy, EM provides pathognomonic findings of GBM lamellation and thinning that often precede or guide genetic testing. Additionally, EM identifies organized deposits in fibrillary and immunotactoid glomerulopathies and helps differentiate diabetic glomerulosclerosis from mimickers through assessment of GBM thickening and matrix expansion. Despite advances in molecular diagnostics, EM remains essential for identifying subtle ultrastructural changes, validating immunopathologic interpretations, and guiding clinical management. This article reinforces EM's continued relevance in an era of expanding genetic and serologic tools.