Increased albumin permeability in vitro following alterations of glomerular charge is mediated by the cells of the filtration barrier

The charge-related determinants of albumin permeability have been the subject of much controversy. We have examined the permeability of either isolated glomerular basement membrane (GBM) or intact glomeruli in an in vitro filtration system to determine the effects of biochemical modifications selected to alter the molecules commonly implicated in restricting the glomerular permeability of anionic macromolecules such as albumin. Treatment of isolated GBM with heparatinase to remove heparan sulfate proteoglycan anionic side chains or profamine to effect charge neutralization had no effect on the albumin sieving coefficient. Protamine decreased hydraulic conductivity. pH titration to encompass the isoelectric point of GBM and albumin resulted in a modest increment in albumin permeability. In contrast, when intact glomeruli were treated with either heparatinase or protamine, albumin permeability doubled and protamine treatment of glomeruli resulted in an even greater augmentation of albumin permeability. These results suggest that, to the extent that in vitro GBM is similar to in vivo GBM, the restriction in albumin permeability due to glomerular charge requires the presence of glomerular cells.