Do large pores in the glomerular capillary wall account for albuminuria in nephrotic states?

Albuminuria in nephrotic states is thought to arise from the formation of large pores in the glomerular capillary wall (GCW) as large hydrodynamic probes, like Ficoll, have increased fractional clearance. In this study we test for large pore formation in a novel manner. We account for the rates of plasma elimination as determined for tritium labeled tracers of uncharged polydisperse Ficoll (radii range 35-85 A) and two globular 14C-labelled proteins, albumin (radius 36 A) and IgG (radius 55 A), in control and puromycin aminonucleoside nephrotic (PAN) Sprague-Dawley rats. The plasma elimination rates were then matched to the urinary excretion of these labelled materials (n=7). Albumin and IgG plasma retention rates were identical and far enhanced as compared to the retention rates of inert transport markers of equivalent hydrodynamic radius; their elimination rate corresponded to the elimination of a 75 A radius Ficoll (n=5) and >105 A radius dextran (n=5). In PAN they were eliminated as 36 A and 55 A Ficoll respectively equivalent to their hydrodynamic radii. In contrast there was no comparable increase in the elimination rate of Ficoll in PAN. The total plasma clearance of Ficoll in control and PAN rats and the urinary clearance in PAN rats was essentially the same for all radii. On the other hand the urinary clearance of Ficoll >45 A radii in controls was considerably lower with increasing radii demonstrating a post-filtration cellular uptake in controls, which when inhibited in nephrotic states, would account for apparent large pore formation.