Effects of glomerular filtration rate on Ficoll sieving coefficients (θ) in rats

Abstract

The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients (theta) to neutral fluorescein isothiocyanate (FITC)-Ficoll 70/400 obtained at low (hydropenic) vs raised (normal) glomerular filtration rates (GFRs). The theta for FITC-Ficoll was determined in anesthetized Wistar rats (304 +/- 18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.2 +/- 0.16 ml/min (+/- s.e.), assessed using the plasma to urine clearance of FITC-inulin and (51)Cr-ethylenediaminetetraacetic acid. FITC-Ficoll 70/400 was infused intravenously (i.v.) following an initial bolus dose. To raise GFR, to an average of approximately 2 ml/min, 5 ml of serum together with glucagon (3 microg/min) was given i.v. FITC-inulin and FITC-Ficoll were determined in plasma and urine using size-exclusion high-performance liquid chromatography. The theta for Ficoll as a function of Stokes-Einstein radius was significantly reduced in the range of 13-43 A when GFR was raised. The maximal theta lowering effect, in relative terms, of raising GFR was obtained for a Ficoll a(e) of approximately 32 A. For Ficoll(36 A) (cf. albumin), theta was reduced from 0.111+/- 0.009 to 0.081+/- 0.012 (P < 0.05; n = 7) for the GFR increment imposed. The reduction in theta for Ficoll after raising GFR indicates the presence of a high diffusive component of glomerular Ficoll filtration in rats in vivo and contradicts the notion of a significant concentration polarization effect in the glomerular filter upon Ficoll molecules < 50 A in radius.

Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo

“…We do not believe this contributes to the observed result because the difference at 2 h was neither large nor statistically significant between treatments or between CA/CPR-exposed mice and CA/CPR-naive mice. Although we describe a defect in glomerular integrity induced by CA/CPR, the methods we (36,41) have employed in vivo do not allow us to localize the effect precisely to the mouse glomerular endothelium, although the in vitro results of this study suggest that is a potential site of barrier disruption. Finally, we measured permeability to Ficoll-70 because it is uncharged and neither secreted nor reabsorbed.…”

“…Finally, we measured permeability to Ficoll-70 because it is uncharged and neither secreted nor reabsorbed. We speculate that the observed effect extends to albumin and other similarly sized physiological mediators, as has been observed in other models (36,41).…”

Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats

“…The exact mechanisms of the described rapid, dynamic changes of the glomerular permeability are at present unknown, leaving room for speculation. Previous results from our group strongly indicate that the major barrier to protein permeability of the glomerular filter is not at the podocyte slit diaphragm (10,23). Thus it seems that all three sequential barriers, i.e., the glomerular basement membrane (GBM) and the two cellular layers, need to interact to create the nearly perfect glomerular permeability barrier normally present (7).…”

Counterpoint: Defending Pore Theory

“…Even though such a perturbation is small, due to the rather moderate electrical charge in the GFB, it still is critical in preventing albumin (radius 35.5 Å) from permeating the "small pore" pathways, having a radius of 37.5 Å. Thus, 37.5 Å -1.5 Å = 36 Å (apparent charged small pore radius) and 35.5 Å + 1.5 Å = 37 Å (apparent "charged" albumin radius), with the consequence that the passage of albumin will normally occur only through a "large pore" pathway (radius ~110 -120 Å) in the GFB (6,7,17).…”

“…Ficoll, a co-polymer of sucrose and epichlorohydrine, apparently shows glomerular sieving characteristics somewhere in between those of dextran and proteins, at least for molecular radii (a e ) approaching the pore radius (r p ) (5). However, for certain ranges of molecular radii (a e /r p < 0.65), Ficoll and proteins have actually been found to have similar glomerular permeation characteristics (7,8). High molecular weight Ficoll, passing through "large pores" (see below; a e /r p < 0.65), like albumin (7), has therefore been frequently used for assessments of glomerular permeability (9)(10)(11)(12).…”