Ultrastructural model for size selectivity in glomerular filtration

A theoretical model was developed to relate the size selectivity of the glo merular barrier to the structural characteristics of the individual layers of the capillary wall. Thicknesses and other linear dimensions were evaluat ed, where possible, from previous electron microscopic studies. The glomeru lar basement membrane (GBM) was represented as a homogeneous material chara cterized by a Darcy permeability and by size-dependent hindrance coefficien ts for diffusion and convection, respectively; those coefficients were esti mated from recent data obtained with isolated rat GEM. The filtration slit diaphragm was modeled as a single row of cylindrical fibers of equal radius but nonuniform spacing. The resistances of the remainder of the slit chann el, and of the endothelial fenestrae, to macromolecule movement were calcul ated to be negligible. The slit diaphragm was found to be the most restrict ive part of the barrier. Because of that, macromolecule concentrations in t he GEM increased, rather than decreased, in the direction of flow. Thus the overall sieving coefficient (ratio of Bowman's space concentration to that in plasma) was predicted to be larger for the intact capillary wall than f or a hypothetical structure with no GBM. In other words, because the slit d iaphragm and GBM do not act independently, the overall sieving coefficient is not simply the product of those for GEM alone and the slit diaphragm alo ne. Whereas the calculated sieving coefficients were sensitive to the struc tural features of the slit diaphragm and to the GEM hindrance coefficients, variations in GEM thickness or filtration slit frequency were predicted to have little effect. The ability of the ultrastructural model to represent fractional clearance data in vivo was at least equal to that of conventiona l pore models with the same number of adjustable parameters. The main stren gth of the present approach, however, is that it provides a framework for r elating structural findings to the size selectivity of the glomerular barri er.