title: Quantitating glomerular endothelial fenestration: an unbiased stereological approach.
abstract: OBJECTIVE
  Glomerular endothelial cells are fenestrated, allowing for especially high transcellular hydraulic conductivity. Current knowledge about endothelial fenestration structural changes in disease conditions is limited, partly due to the absence of robust methodologies to quantitate these structures. Herein, we propose a novel method for estimating the percentage of endothelial fenestration.
  
  
  METHODS
  An unbiased stereological method based on contiguity of two phases and surface area density estimation using isotropic uniform random line probes was developed. A line grid for intercept counting and classifying endothelial coverage of fenestrated versus non-fenestrated areas was designed. The method was applied to renal biopsies from 15 patients with Fabry disease and 9 normal living kidney donor controls.
  
  
  RESULTS
  The percentage of glomerular capillary endothelial coverage which was fenestrated was lower in Fabry patients (43 ± 12%) versus controls (53 ± 9%; p = 0.047). The fraction of endothelial surface which was fenestrated was greater on the peripheral versus mesangial zones of the capillary walls in both Fabry patients (p = 0.00002) and controls (p = 0.0005).
  
  
  CONCLUSIONS
  The proposed method provides an unbiased tool to quantitate endothelial fenestration changes in glomeruli. The practical example introduced showed reduced glomerular endothelial fenestration in Fabry nephropathy.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA. najafian@uw.edu
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
mesh_terms: D000293:Adolescent; D000328:Adult; D002196:Capillaries / Q000473:pathology* / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000473:pathology* / Q000648:ultrastructure; D000795:Fabry Disease / Q000473:pathology*; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D055815:Young Adult