Glomerular size and charge selectivity in the rat as revealed by FITC-Ficoll and albumin

Abstract

The fractional clearances (theta) for FITC-Ficoll and albumin were estimated in isolated perfused rat kidneys in which the tubular activity was inhibited by low temperature (8 degrees C) and/or 10 mM NH(4)Cl. The Ficoll data were analyzed according to a two-pore model giving small and large pore radii of 46 A and 80-87 A, respectively. The estimated negative charge density was 35-45 meq/l at 8 degrees C. Perfusion with erythrocyte-free solutions of kidneys at 37 degrees C reduced glomerular size and charge permselectivity. Thus the large pore fraction of the glomerular filtrate (f(L)) was 1.64% at 37 degrees C compared with 0.94% at 8 degrees C. The theta for albumin was four times higher at 37 degrees C than at 8 degrees C (0.86% vs. 0.19%, respectively). NH(4)Cl caused further irreversible damage to the glomerular barrier. We conclude that there are no deleterious effects on the glomerular barrier of a reduction in temperature from 37 degrees C to 8 degrees C. Therefore our data seem to disprove the hypothesis of low glomerular permselectivity and transtubular uptake of intact albumin and support the classic concept of a highly selective glomerular barrier.

Functional and molecular alterations of the glomerular barrier in long-term diabetes in mice

“…The results regarding pore sizes and charge density in controls are well in accord with previous studies in our laboratory on rats [8,25,41,42] and mice [9], both in vivo and in the cIPK model. The fractional clearance for Ficolls larger than~50 Å is approximately one order of magnitude larger in the cIPK compared with in vivo.…”

“…To overcome these limitations, one may use the inert polysaccharides dextran or Ficoll as markers instead of albumin. Alternatively, the tubular processes may be inhibited by toxins [24], but such drugs seem to affect permeability per se [25]. At present, one of the most reliable estimates of glomerular filtration is obtained by using the cooled isolated perfused kidney (cIPK) model, either in rats [4,8,26] or in mice [9].…”

Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion

“…Reported values in the literature are 3.0 to 3.5 nm, 37,38,51 1 to 7 nm, 8 and 6.4 nm, 48 respectively. The similarity between albumin and ficoll suggest that, in solution, ficoll exists as a sphere.…”

Illuminating the Glomerular Filtration Barrier, Two Photons at a Time

“…However, because clinicopathologic and genetic data were most consistent with a glomerular barrier, a significant role for tubular albumin transport was difficult to integrate with prior models of renal physiology. 19,31,32 In an attempt to gain insight into the ongoing controversy by using a new technique, the work by Russo et al 11 employed the recently developed toolkit of two-photon intravital microscopy to determine the concentration of albumin in Bowman's capsule and measured a glomerular sieving coefficient for albumin (GSC A ) of about 0.034 (or 50-to 100-fold higher than the coefficient determined from micropuncture studies). Furthermore, rats treated with puromycin aminonucleoside display reduced proximal tubule brush border albumin uptake and little change in GSC A .…”

“…Similar-sized polysaccharide molecules, such as ficoll, are hindered by the glomerular capillary wall to a lesser extent than albumin. 18,19 However, measurements of macromolecular transport through well-defined artificial membranes or agarose gels have not shown similar discrepancies, and the differential in sieving coefficient between albumin and ficoll is much less pronounced in other capillary beds.…”