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A heteroporous model of the glomerular filtration barrier was developed and used to interpret dextransieving data in healthy volunteers (normal controls), in patients with nephrotic range proteinuria (grouped as grades I-III, according to severity), and in a group of previously nephrotic patients whose proteinuria was in remission ("resolved controls"). Several hypothetical pore-size distributions were compared in terms of their ability to describe the selective increases in the fractional clearance of large dextrans observed with increasing severity of proteinuria. The most successful model examined was based on the assumption that the major portion of the capillary wall functions as an isoporous membrane, but that a small fraction of the filtrate passes through pores that are unable to discriminate among dextrans of different sizes. The value of the membrane parameter that reflects the relative importance of the nonselective pores was found to increase in parallel with the fractional clearance of immunoglobulin G; it increased progressively in going from normal controls to resolved controls to grades I-III nephrotics. The observed patterns of protein excretion could not, however, be explained entirely by a loss of glomerular size selectivity. Variations in membrane selectivity on the basis of molecular charge and/or molecular configuration are also likely to have been important.

The formation of glomerular ultrafiltrate is dependent on the interplay of glomerular pressures and flows as well as the intrinsic permselectivity properties of the glomerular capillary wall. These intrinsic permeability properties serve to exclude macromolecules from the urinary space, based on size as well as net molecular charge discrimination. Neutral dextrans with molecular radii less than 20 A cross the glomerular wall without measurable restriction, whereas dextrans with radii greater than 42 A are almost completely barred. For any given size, negatively charged macromolecules are restricted to a greater extent than neutral molecules. Additionally, positively charged molecules are enhanced in their ability to cross the glomerular wall compared to similarly sized neutral polymers. The concept of a charge barrier, due to fixed negative charges within the glomerular wall, is also supported by morphological studies. Glomerular injury, leading to proteinuria, has been associated with loss of the charge-selective properties of these capillaries. Loss of glomerular fixed negative charges may also result in the foot process fusion and mesangial cell dysfunction often observed in proteinuric states.

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