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

Aims/hypothesis. Changes in podocyte number and morphology have been implic ated in the pathogenesis of proteinuria and the progression of human and ex perimental kidney disease. This study sought to examine podocyte foot proce ss and slit pore architecture in experimental diabetic nephropathy and to d etermine whether such changes were modified with renoprotective interventio n by blockade of the renin-angiotensin system. Methods. The number of filtration slits per 100 mum of glomerular basement membrane was assessed by transmission electron microscopy and quantitated h istomorphometrically in control animals and in rats with 24 weeks of strept ozotocin-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 basemen t membrane, indicative of podocyte foot process broadening. Both ramipril a nd valsartan attenuated these ultrastructural changes to a similar degree. These differences remained after correcting for glomerular volume as a poss ible confounding variable. Conclusion/interpretation. Preservation of podocyte architecture could cont ribute to the renoprotective effects of renin-angiotensin system blockade i n diabetic nephropathy.