Ultrastructure of the glomerular basement membrane of rats with proteinuria due to subtotal nephrectomy

Subtotal nephrectomy in the rat gives rise to progressive proteinuria, glomerular hypertrophy, and glomerulosclerosis. The proteinuria antedates significant ultrastructural lesions demonstrable by conventional techniques; its mechanism is obscure. In this article it is shown that proteinuria in this system is not accompanied by evident changes in the ultrastructural distribution of anionic sites in the glomerular basement membrane, as determined by organ perfusion with two cationic probe molecules. It is suggested that the proteinuria may reflect a change in the steric aspect of glomerular ultrafilration, in which the loss of renal mass imposes a significant rise in capillary pressure in a structure whose capillaries are peculiar in the high pressures they normally sustain and in their lack of mechanical support from the interstitium. It is suggested that a sustained rise in capillary pressure overcomes the rigidity of the glomerular basement membrane, so that its pore size increases and proteinuria results from basement membrane failure.