Glomerular endothelium in kidneys with congenital nephrotic syndrome of the Finnish type (NPHS1).

BACKGROUND: The role of glomerular capillary endothelium in the pathophysiology of nephrotic kidney diseases is poorly known. We analysed the glomerular endothelial lesions in kidneys from patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The disorder is caused by a genetic defect in a major podocyte slit diaphragm protein, nephrin. It manifests as nephrotic syndrome soon after birth and leads to glomerular sclerosis in early childhood.

METHODS: The glomerular capillary and endothelial cell lesions in NPHS1 kidneys nephrectomized at infancy were studied by electron and light microscopy, immunohistochemistry and cytokine antibody array.

RESULTS: Mesangial expansion and capillary obliteration were evident in practically all NPHS1 glomeruli. No thrombus formation was detected by fibrin staining. Electron microscopy revealed endothelial blebs (endotheliosis). The endothelial fenestration and the attachment of endothelial cells to the basement membrane were, however, quite normal. This fits to the abundant expression of a vascular endothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1alpha (HIF-1alpha), in NPHS1 glomer- uli. The proliferative activity of the intracapillary cells was modest and no apoptosis was detected. The expression of an endothelial adhesion molecule, intercellular adhesion molecule 1 (ICAM-1) and several chemokines was upregulated in NPHS1 glomeruli as compared to adult control kidneys. The recruitment of leukocytes carrying ligands for the major endothelial adhesion molecules, however, was modest in the mesangial area of NPHS1 glomeruli.

CONCLUSIONS: The findings indicate that the glomerular endothelium is quite resistant to the nephrotic state in NPHS1 kidneys and underscores the importance of mesangial cells in the progression of glomerular sclerosis.