Basal lamina secreted by MDCK cells has size- and charge-selective properties

Computer Programs in Biomedicine, 1975

The transport of water and of macromolecules across the glomerular membrane of the kidney depends on the membrane parameters (radius, length and number of pores) as well as on the hydrostatic and oncotic pressures on either side of the membrane. The filtration pressure decreases along the capillary loops from afferent to efferent end. Water and solute flows are thus given by a system of two differential equations.

American journal of physiology. Renal physiology, 2003

In a previous paper, we found that low ionic strength (I) reversibly reduced the glomerular charge density, suggesting increased volume of the charge-selective barrier. Because glutaraldehyde makes most structures rigid, we considered the isolated, perfusion-fixed rat kidney to be an ideal model for further analysis. The fixed kidneys were perfused with albumin solutions containing FITC-Ficoll at two different Is (I = 151 and 34 mM). At normal I, the fractional clearance () for albumin was 0.0049 (SE -0.0017, +0.0027, n = 6), whereas for neutral Ficoll35.5A of similar size was significantly higher 0.104 (SE 0.010, n = 5, P < 0.001). At low I, for albumin was 0.0030 (SE -0.0011, +0.0018, n = 6, not significant from albumin at normal I) and for Ficoll35.5A was identical to that at normal I, 0.104 (SE 0.015, n = 6, P < 0.01 compared with albumin at low I). According to a heterogeneous charged fiber model, low I reduced the fiber density from 0.056 to 0.0315, suggesting a 78% gel ...

Pfl�gers Archiv European Journal of Physiology, 1999

The charge-related determinants of albumin permeability are the subject of controversial discussion. To study this question we have developed an isolated perfused rat kidney model in which metabolic processes are eliminated by perfusion fixation with glutaraldehyde. The fixed kidneys were perfused with albumin solutions using the following approaches: 1. Modification of the charge of both the glomerular capillary wall (GCW) and albumin using different buffer systems in a pH range spanning the isoelectric points of albumin and the glomerular basement membrane (GBM), the extracellular matrix of the GCW. 2. Modification of the charge of the GCW by perfusing the isolated kidney with cations either before or after fixation. 3. Modification of the charge of albumin by cationization. In the model, the inulin "urine" to perfusate ratio was one. This shows that the tubules have no metabolic activity, that the glomerular filtration rate (GFR) is equal to "urine" flow rate and that the "urine" collected is identical to the ultrafiltrate. Therefore, sieving coefficients in this model can simply be calculated as the ratio between "urine" and perfusate protein concentrations. We could show that: 1. pH has a significant effect on the albumin sieving coefficient: it was maximally increased at pH 4.0 [(70.3±15.9)×10 -3 , n=10 versus (8.7±3.7)×10 -3 , n=11, at pH 7.4]. Only a pH as low as 4.0 should lead to a pronounced neutralization of the anionic charges of albumin and the GBM; the charge density of the GCW calculated with these data is 43 mEq/l at pH 7.4. 2. Modifying the ionic composition of the GCW with protamine before fixation with glutaraldehyde causes a bigger increase in the glomerular permeability for albumin [(51.2±22.5)×10 -3 , n=10, glomerular charge density 21 mEq/l] than modifying the albumin charge by cationization. 3. Modifying the albumin charge by cationization increases the glomerular permeability for albumin [(20.0±6.7)×10 -3 , n=8]. These findings support the hypothesis that at the onset of proteinuria changes in the charge and configuration of the GCW could be more important pathogenetic factors than changes in the charge of serum-derived proteins.

1982

is an as.sistant in thi-Dcpartnii-nt ot I rolog y, Facultv of Mcdit inc. Universitv of Hannover. Fédéral Repub lii of Ck-rmany; Dr. Bergmann is a research assixiale witfi llie Qiicen F.lisaf)eth NIedIcal Foundation. Bru.ssels, Bclgium. Onlv Dr. I.anitx-rl atteiided ihe conférence. The aiilhors wisli to acknowlcdge the c(>llatx)ration ol the following individuals: F. Hanus. S. IVgof'f, and M. Van Damnie. for dcvelopnient of the network niodel of glomerular circulation; M. Lammens-Vcrslijpe. R. \'an Holder and J. Sennesael, for sieviiig studies on dogs; C:. .N'guven Huu and R. Du Bois, for development of the theorctical inodel of charge seicctivity; M. Landuyt for electrophoretic mob ilities of the DS fractions; and M. Doriaux for the morphological study of the rénal damage produced b v the inf usion of c.itionized seriim alb umin.

2010

Clearance studies using various probe molecules established that the passage of molecules/proteins across the glomerular capillary wall of mammalian kidneys is increasingly restricted as their size and net negative charge increase. An extended mathematical model, based on the Fiber Matrix theory, was developed to describe the dynamics of the size- and charge-selective functions of the glomerular capillary barrier using mainly its hemodynamic, morphometric, and electrostatic variables. The glomerular basement membrane was represented as a homogeneous three-dimensional network of fibers of uniform length (L(f)), radius (R(f)), and packing density (N(fv)) and characteristic Darcy permeability. The model was appropriate for simulating in vivo fractional clearance data of neutral and charged Ficoll solutes from an experimental rat model. We believe that the L(f) and R(f) best-fit numerical values may signify new insights for the diagnosis of some human nephropathies.

Kidney Int, 1984

Size and charge selective permeability defects induced in glomerular basement membrane by a polycation. Polyethyleneimine (PEI) was given intravenously to rats followed by native ferritin or one of three cationic ferritins. After 15 min kidneys were fixed for electron microscopy. ...

Journal of the American Society of Nephrology, 2010

There is ongoing controversy about the mechanisms that determine the characteristics of the glomerular filter. Here, we tested whether flow across the glomerular filter generates extracellular electrical potential differences, which could be an important determinant of glomerular filtration. In micropuncture experiments in Necturus maculosus, we measured a potential difference across the glomerular filtration barrier that was proportional to filtration pressure (Ϫ0.045 mV/10 cm H 2 O). The filtration-dependent potential was generated without temporal delay and was negative within Bowman's space. Perfusion with the cationic polymer protamine abolished the potential difference. We propose a mathematical model that considers the relative contributions of diffusion, convection, and electrophoretic effects on the total flux of albumin across the filter. According to this model, potential differences of Ϫ0.02 to Ϫ0.05 mV can induce electrophoretic effects that significantly influence the glomerular sieving coefficient of albumin. This model of glomerular filtration has the potential to provide a mechanistic theory, based on experimental data, about the filtration characteristics of the glomerular filtration barrier. It provides a unique approach to the microanatomy of the glomerulus, renal autoregulation, and the pathogenesis of proteinuria.

Journal of Ultrastructure Research, 1976

Current Opinion in Nephrology and Hypertension, 2012

Purpose of review Each day, the human kidneys filter about 140 l of primary urine from plasma. Although this ultrafiltrate is virtually free of plasma protein, the glomerular filter never clogs under physiological conditions. Upto today it is still not entirely resolved as to how the kidney accomplishes this extraordinary task. Most of the proposed models for glomerular filtration have not considered electrical effects. Recent findings In micropuncture studies, we have directly measured an electrical field across the glomerular filtration barrier. This potential difference is most likely generated by forced passage of the ionic solution of the plasma across the charged glomerular filter ('electrokinetic potential'). As all plasma proteins are negatively charged, the electrical field across the glomerular filtration barrier is predicted to drive plasma proteins from the filter toward the capillary lumen by electrophoresis.

AJP: Renal Physiology, 2009

Many aspects of the glomerular filtration of macromolecules remain controversial, including the location of the major filtration barrier, the effects of electrical charge, and the reason the filtration barrier does not clog. We examined these issues in anesthetized Necturus maculosus, using fluorescently labeled probes and a two-photon microscope. With the high resolution of this system and the extraordinary width (∼3.5 μm) of the glomerular basement membrane (GBM) in this salamander, we were able to visualize fluorescent molecules in the GBM in vivo. GBM/plasma concentration ratios for myoglobin, ovalbumin, and serum albumin did not differ from that of inulin, indicating that the GBM does not discriminate among these molecules. The GBM/plasma concentration ratios for fluoresceinated dextran 500 and 2,000 kDa were significantly below that of inulin. Glomerular sieving coefficients (GSCs) for various macromolecules decreased as molecular mass increased, and the GSCs for bovine or hum...