Glomerular microangiopathy can be associated with nephrotic proteinuria due to both segmental effacement of foot processes and damage to the glomerular endothelial barrier.

Authors

Casey P Schukow, Carley J Holmes, Wei Li, Hassan D Kanaan, Ping L Zhang

Published in

Ultrastructural pathology. Pages 1-9. Nov 12, 2026. Epub Nov 12, 2026.

Abstract

Glomerular microangiopathy (GMA)-caused by etiologies including VEGF inhibition, thrombotic microangiopathy, or malignant hypertension-is frequently linked to nephrotic-range proteinuria. However, the mechanisms of severe proteinuria following glomerular filtration barrier injury remain unclear. We examined how podocyte and glomerular endothelial injury relate to significant proteinuria in GMA. Thirty-seven kidney biopsies were studied, including 10 negative controls (Group 1), 11 GMA cases associated with VEGF inhibition (Group 2), and 16 GMA cases caused by other etiologies (Group 3). Electron microscopy was used to quantify foot process effacement and assess glomerular endothelial injury. To further evaluate endothelial barrier dysfunction, Oil Red O (ORO) staining for lipoprotein deposition and colloidal iron staining for negatively charged proteoglycans were performed. Correlations between ultrastructural changes and proteinuria were analyzed statistically. Nephrotic-range proteinuria was observed in 82% (9/11) of Group 2 and 56% (9/16) of Group 3 cases. In both groups, the severity of proteinuria was significantly associated with the extent of foot process effacement, endothelial edema and detachment, and GBM double-contour formation. ORO staining demonstrated subendothelial lipoprotein accumulation along the GBM in GMA cases but not in controls, consistent with increased glomerular endothelial permeability. In addition, colloidal iron staining was markedly reduced along the GBM in GMA, indicating impaired charge-selective properties of the glomerular filtration barrier. Significant proteinuria in GMA is associated with concurrent podocyte and glomerular endothelial cell injury. Ultrastructural findings, subendothelial lipoprotein accumulation, and reduced GBM proteoglycan staining indicate that endothelial barrier dysfunction, alongside podocyte injury, contributes critically to nephrotic-range proteinuria in GMA.

PMID:
43018434
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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