Effects of filtration rate on the glomerular barrier and clearance of four differently shaped molecules

Abstract

The effect of shape on the transglomerular passage of solutes has not been hitherto systematically studied. We perfused isolated rat kidneys to determine the fractional clearances (theta) at various filtration rates for four molecules of different shapes but with similar Stokes-Einstein radii (aSE = 34-36 A). The theta for hyaluronan, bikunin, and Ficoll36 A were 66, 16, and 11%, respectively, at a glomerular filtration rate (GFR) of 0.07 ml x min(-1) x g wet wt(-1) and decreased to 46, 14, and 7%, respectively, on a fivefold increase in GFR. Under the same conditions, theta for albumin increased from 0.15 to 0.74%, and similar behavior was observed for larger Ficolls (aSE >45 A). Pore analysis showed that the "apparent neutral" solute radii of Ficoll, albumin, bikunin, and hyaluronan were 35, 64, 33, and 24 A, respectively, despite similar aSE. In addition, the properties of the glomerular filter changed with increasing GFR and hydrostatic pressure. We conclude that elongated shape, irrespective of size and charge, drastically increases the transglomerular passage of a solute, an effect that is related to its frictional ratio.

Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys

“…Only at high GFRs, the impact of the diffusional component will become negligible, so that the protein will equal (1 Ϫ ) (7,8,20,21,23,33). Contrary to results from the IPK (19), there were no indications of increases in microvascular permeability occurring for albumin at high intraglomerular hydrostatic pressures in the present study. A tentative explanation could be that the IPK, although partly protected from inflammatory mediators or ischemia-reperfusion injury by the temperature reduction, might be more vulnerable to high intraluminal pressures than is the intact kidney under in vivo conditions.…”

“…In the isolated perfused rat kidney (IPK) at 8°C, however, there is one recent set of measurements of this kind for "asymmetrical" proteins (19). Although in the IPK the GFR (per kidney) was only 20% of those obtained at 37°C in the intact rat in vivo, the observed for the most permeable proteins investigated (hyaluronan and bikunin) showed a similar asymptotic reduction as a function of GFR, as found in the present study.…”

New Hydrolysis-Dependent Thermosensitive Polymer for an Injectable Degradable System

“…The time-dependent LCST result is another evidence showing that this new copolymer, poly(NIPAAm-co-dimethyl-γ-butyrolactone) should be bioerodible. Future work will also be focused on optimizing the original LCST, accelerating the hydrolysis process for drug delivery and tissue engineering applications, evaluating polymers with appropriate size and shape for kidney clearance for in vivo application, 25 and investigating the in vitro and in vivo cytotoxicity/biocompatibility of these materials. The model supports the hypothesis that the hydrolysis is self-catalytic.…”

Elevated urinary excretion of immunoglobulins in nonproteinuric patients with type 1 diabetes

“…The glomerular filtration barrier consists of three components: endothelium, negatively charged basement membrane, and the podocyte slit diaphragm, functioning together as a size- (8,13), but the most accepted one speculates on the presence in healthy individuals of some number of the small pores that allow albumin leakage, a minimal number of large pores that could potentially allow the leakage of larger proteins as IgG, and hardly any shunts that would allow IgM excretion (8,21). By demonstrating the presence of IgG as well as IgM in the urine of our study subjects, we support the theory of an existence of Significance between the groups was tested by analysis of variance (SAS command, proc glm/lsmeans) with urinary Igs adjusted by creatinine and transformed to its logarithms (base 10) as a dependent variable, whereas groups HS, NA, and MA were considered as independent class variables in the model.…”