Glomerular permselectivity: barrier function based on discrimination of molecular size and charge

Abstract

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.

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

“…On the other hand, hydrophilic drugs with low molecular size are subjected to high renal clearance. Hence, the molecular size of such drugs must be high enough to avoid immediate excretion (Brenner et al 1978, Maack et al 1979. If EGF is linked to saporin (1:1) through a simple disulfide bridge, this would result in a ~40…”

Morpho-functional studies of the blood-brain barrier in streptozotocin-induced diabetic rats

“…Due to their impact on the pathology of diabetes, several studies have focused on the changes occurring at the level of the renal glomerular wall showing alteration in renal filtration properties with extravasation of serum proteins [13,14,15,24]. Mechanisms responsible for the glomerular permselectivity, such as size restriction, charge repulsion and molecular configurations of the basement membrane components have been found to undergo major changes [18,25,26,27,28]. Similar alterations could take place at the blood-brain barrier, since loss of its integrity has already been documented during diabetes [29,30,31,32] with changes in CNS blood capillary density [29,33] and capillary basement membrane thickening [34,35,36,37].…”

Counterpoint: Defending Pore Theory

“…Based on these results, we recently quantified the electrostatic properties of the GFB in terms of surface charge density, modeling the glomerular barrier as a negatively charged fiber-matrix according to the model in (15). We estimated the fiber surface charge to be similar to that of known surface charge densities for many proteins in the FIGURE 1 -"New" (A) and "old" (B) "Brenner curves" (1). Panel A shows recent data on glomerular sieving coefficients measured for anionic and neutral Ficoll and simulated for cationic Ficoll (14).…”