Congenital nephrotic syndrome of the Finnish type (NPHS1) is associated with the rapid development of glomerular and tubulointerstitial fibrosis. Here we measured morphologic and molecular changes in the peritubular capillaries of the kidney in patients with NPHS1. Immunohistochemical analysis for the endothelial cell marker CD31 showed marked narrowing and a moderate but significant reduction in peritubular capillary density, especially in areas of increased collagen I and alpha-smooth muscle actin content. No evidence of endothelial-mesenchymal transformation was found. There was increased expression (up to 43-fold) of hypoxia inducible factor-1alpha suggesting tubulointerstitial hypoxia. Double-labeling for CD31 and vimentin showed small foci of peritubular capillary loss and tubular cell damage. While the amount of intercellular adhesion molecule-1 was upregulated in endothelial cells, other adhesion molecules were only modestly expressed. Vascular endothelial growth factor expression was reduced by up to half and decreased endothelial progenitor cell marker CD34 expression indicated lack of vascular repair. Our results suggest that hypoxia in the tubulointerstitium caused by hypoperfusion of glomerular and tubulointerstitial capillaries and rarefaction of the latter may be important for the rapid progression of fibrosis in the kidneys of patients with NPHS1.