The glomerular barrier fits a two-pore-and-fiber-matrix model: derivation and physiologic test

Failure of the glomerular barrier causing proteinuria has been modeled chiefly by Chang, Deen, and Brenner. They have refined models from an isoporous filter to a mostly isoporous membrane, which during proteinuric disease opens up nondiscriminating shunts. This report extends these concepts by measuring a larger distribution of macromolecular tracer sizes and bringing in a fiber matrix. By clearance methods, glomerular sieving curves of relatively neutral tetramethyl rhodamine aminodextran from radii of 15 to over 80 A were obtained and fitted to theory. Two pores filled with matrix fit all data without exception, and no other model did. Five parameters described the curve in control rats and in proteinuric rats made so by albumin injections. From highest to lowest degree of confidence, these were small and large pore radii ros = 42.7 +/- 0.9 SEM A and rol = 926 +/- 156 A; small to large pore density ns/nl = 3859 +/- 942; mean fiber radius rf = 20.3 +/- 1. 1 A; and fiber void volume ratio epsilon = 0.52 +/- 0.05. In proteinuria, ros rose 13% (P = 0.002), nl increased 150% (P = 0.04), and there was a compensatory rise in rf of 26% (P = 0.002). The consideration of basement membrane and glycocalyx remain to be incorporated into the model. Moreover, the closeness of rf to ros indicates that fiber matrix theory may need modification for a complete description.