Charged compounds of the glomerular filter and their role in normal and disordered permselectivity

Infusion into rats of the polycation hexadimethrine (HDM) leads to onset of massive proteinuria, which recovers when the infusion is stopped. Several lines of evidence indicate that the proteinuria results from binding of HDM to polyanions of the glomerular filter, with neutralization of shielding of their charges. To determine the mechanism of this proteinuria, we measured the glomerular sieving coefficients of anionic and neutral forms of albumin and IgG in control and proteinuric rats. Surprisingly, these studies revealed a marked defect in size dependence, but not in charge dependence, of glomerular permselectivity in hexadimethrine-treated animals, indicating that binding of HDM induces a structural change in the glomerular filter. In vitro studies of binding of tritiated HDM and cationized ferritin to glomerular basement membrane (GBM) indicate that the binding is not dependent on proteoglycans such as heparan sulfate, nor on sialoproteins such as podocalyxin, but is dependent on charged carboxyl groups of GBM.