Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade

Diabetologia. 2001 Jul;44(7):878-82. doi: 10.1007/s001250100561.


Aims/hypothesis: 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.

Conclusion/interpretation: Preservation of podocyte architecture could contribute to the renoprotective effects of renin-angiotensin system blockade in diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Basement Membrane / drug effects
  • Basement Membrane / ultrastructure
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Male
  • Organ Size / drug effects
  • Ramipril / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*
  • Tetrazoles / therapeutic use*
  • Valine / analogs & derivatives*
  • Valine / therapeutic use*
  • Valsartan


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Tetrazoles
  • Valsartan
  • Valine
  • Ramipril