title: Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade.
abstract: OBJECTIVE
  Changes in podocyte number and morphology have been implicated in the pathogenesis of proteinuria and the progression of human and experimental kidney disease. This study sought to examine podocyte foot process and slit pore architecture in experimental diabetic nephropathy and to determine whether such changes were modified with renoprotective intervention by blockade of the renin-angiotensin system.
  
  
  METHODS
  The number of filtration slits per 100 microm of glomerular basement membrane was assessed by transmission electron microscopy and quantitated histomorphometrically in control animals and in rats with 24 weeks of streptozotocin-induced diabetes. Diabetic rats were either untreated or received the angiotensin converting enzyme inhibitor ramipril, or the angiotensin II type 1 receptor antagonist, valsartan.
  
  
  RESULTS
  When compared with control animals, diabetes was associated with a decrease in the number of slit pores per unit length of glomerular basement membrane, indicative of podocyte foot process broadening. Both ramipril and valsartan attenuated these ultrastructural changes to a similar degree. These differences remained after correcting for glomerular volume as a possible confounding variable.
  
  
  CONCLUSIONS
  Preservation of podocyte architecture could contribute to the renoprotective effects of renin-angiotensin system blockade in diabetic nephropathy.
authors.affiliation: Department of Physiology, University of Melbourne, Victoria, Australia.
authors.forename: S A
authors.initials: SA
authors.lastname: Mifsud
authors.forename: T J
authors.initials: TJ
authors.lastname: Allen
authors.forename: J F
authors.initials: JF
authors.lastname: Bertram
authors.forename: U L
authors.initials: UL
authors.lastname: Hulthen
authors.forename: D J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: M E
authors.initials: ME
authors.lastname: Cooper
authors.forename: J L
authors.initials: JL
authors.lastname: Wilkinson-Berka
authors.forename: R E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D017257:Ramipril