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

1978 ◽  
Vol 234 (6) ◽  
pp. F455-F460 ◽  
Author(s):  
B. M. Brenner ◽  
T. H. Hostetter ◽  
H. D. Humes
Keyword(s):  
Molecular Size ◽  
Glomerular Injury ◽  
Cell Dysfunction ◽  
Morphological Studies ◽  
Molecular Charge ◽  
Foot Process ◽  
Charged Macromolecules ◽  
A Charge ◽  
Urinary Space ◽  
Positively Charged

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.

Clearance of charged and uncharged dextrans from normal and injured lungs

1990 ◽  
Vol 68 (1) ◽  
pp. 341-347 ◽  
Author(s):  
M. P. Barrowcliffe ◽  
G. D. Zanelli ◽  
D. Ellison ◽  
J. G. Jones
Keyword(s):  
Clearance Rate ◽  
Dextran Sulfate ◽  
Molecular Size ◽  
Confidence Limits ◽  
Half Time ◽  
Capillary Barrier ◽  
Solute Transfer ◽  
Molecular Charge ◽  
Before And After ◽  
Alveolar Capillary

To examine how molecular charge affects the transfer of molecules across the alveolar-capillary barrier, we prepared the following dextrans of equivalent molecular size (mol wt 10,000) but varying molecular charge: neutral dextran, cationic DEAE dextran, and anionic dextran sulfate. These were labeled with 99mTc. The lungs of three groups of anesthetized rabbits were insufflated with dextran aerosols, with six rabbits receiving each type, and the half-time pulmonary clearance (t1/2) was measured. Control t1/2's (95% confidence limits) were 95 (74-120), 227 (192-268), and 291 (246-345) min for neutral, cationic, and anionic dextrans, respectively. One week later, when the same animals were restudied 4 h after 3 micrograms/kg iv endotoxin, t1/2's were 102 (75-139), 167 (149-187), and 126 (102-154) min, respectively. After 30 min during this repeat study, animals were ventilated with 20 breaths of cigarette smoke, which acutely increased the clearance rate to 34 (26-46), 25 (20-31), and 13 (7-24) min, respectively. Mean carboxyhemoglobin levels were not significantly different in the three groups: 13.6, 12.7, and 11.1%, respectively. These results demonstrated that neutral dextrans showed the same clearance rate before and after endotoxin, whereas the charged dextrans had a significantly faster clearance after endotoxin. After smoke exposure the anionic dextran left the lung more rapidly than the neutral dextran. Thus molecular charge affects solute transfer across the alveolar-capillary barrier in both normal and injured lungs, and an effect of endotoxin on the lung can be detected with charged dextrans but not with neutral dextran.

First (3 + 2)-dimensional superspace approach to the structure of levyclaudite-(Sb), a member of the cylindrite-type minerals

2006 ◽  
Vol 62 (5) ◽  
pp. 775-789 ◽  
Author(s):  
Michel Evain ◽  
Vaclav Petricek ◽  
Yves Moëlo ◽  
Colette Maurel
Keyword(s):  
Energy Minimization ◽  
Inorganic Compounds ◽  
Two Dimensional ◽  
X Ray Diffraction ◽  
Layer Compound ◽  
X Ray ◽  
Density Modulation ◽  
Wavelength Control ◽  
A Charge ◽  
Positively Charged

The structure of synthetic levyclaudite-(Sb), approximately (Pb1 − y Sb y S)1.357[Sn1 − x (Cu2) x S2], has been determined by single-crystal X-ray diffraction on the basis of the (3 + 2)-dimensional superspace approach. This misfit-layer compound, of the cylindrite type, results from the combination of two heavily modulated triclinic Q and H subsystems with a common q wavevector and only one shared reciprocal axis (stacking direction). The Q pseudo-tetragonal layer, ∼(Pb0.70Sb0.30S), derived from the NaCl archetype, is positively charged; the H pseudo-hexagonal layer, ∼(Sn0.85Cu0.30S2), derived from the CdI2 archetype, is negatively charged, owing to the replacement of Sn4+ in an octahedral coordination by Cu+ pairs in an opposite triangular coordination. The analysis shows a strong transverse displacive modulation of the two layers, referred to as a `mondulation', correlated to a maximal Sb site occupation factor in the concavity of the Q layer undulation. The wavelength control of the `mondulation' obeys the vernier principle (14cQ ≅ 13cH ), which would correspond to an energy minimization through a charge transfer density modulation wave, common to all two-dimensional misfit-layer inorganic compounds.

scholarly journals Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria

2019 ◽  
Vol 317 (1) ◽  
pp. F12-F22 ◽  
Author(s):  
Li-Hong Zhang ◽  
Xiang-Yang Zhu ◽  
Alfonso Eirin ◽  
Arash Aghajani Nargesi ◽  
John R. Woollard ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Extracellular Vesicles ◽  
Light And Electron Microscopy ◽  
Urinary Concentration ◽  
Glomerular Injury ◽  
Podocyte Injury ◽  
Early Markers ◽  
Nutrient Surplus ◽  
Glomerular Size ◽  
Foot Process

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg−1·day−1 sc) for the last month of diet, and lean controls ( n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.

scholarly journals An intestinal paracellular pathway biased toward positively-charged macromolecules

2018 ◽  
Vol 288 ◽  
pp. 111-125 ◽  
Author(s):  
Khaled Almansour ◽  
Alistair Taverner ◽  
Jerrold R. Turner ◽  
Ian M. Eggleston ◽  
Randall J. Mrsny
Keyword(s):  
Paracellular Pathway ◽  
Charged Macromolecules ◽  
Positively Charged

scholarly journals Loss of Roundabout Guidance Receptor 2 (Robo2) in Podocytes Protects Adult Mice from Glomerular Injury by Maintaining Podocyte Foot Process Structure

2020 ◽  
Vol 190 (4) ◽  
pp. 799-816
Author(s):  
Anna Pisarek-Horowitz ◽  
Xueping Fan ◽  
Sudhir Kumar ◽  
Hila M. Rasouly ◽  
Richa Sharma ◽  
...  
Keyword(s):  
Glomerular Injury ◽  
Adult Mice ◽  
Foot Process ◽  
Process Structure

Effect of Molecular Charge on the Induction of Proteinuria and Glomerular Ultrastructural Damage in Hyperalbuminaemic Female Wistar Rats

1984 ◽  
Vol 66 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Gillian M. Lawrence ◽  
D. B. Brewer
Keyword(s):  
Epithelial Cell ◽  
Tubular Epithelium ◽  
Glomerular Epithelial Cell ◽  
Bovine Albumin ◽  
Protein Excretion ◽  
Molecular Charge ◽  
Female Wistar Rats ◽  
Foot Process ◽  
Ultrastructural Damage ◽  
Process Loss

1. Intraperitoneal injection of anionic carbamylated bovine albumin derivatives induced glomerular epithelial cell foot process loss and increased urinary protein excretion, the severity of which rose with the dose administered. 2. The effects induced at a given albumin dose were significantly lower than those previously measured after the administration of normal bovine albumin. 3. The amount of epithelial cell foot process loss induced after the injection of carbamylated bovine albumin derivatives correlated well with the level of induced proteinuria but, at a given level of proteinuria, the amount of foot process was lower in these rats compared with those given normal bovine albumin. 4. The results obtained are consistent with the interpretation that the more anionic carbamylated bovine albumin derivatives were not only filtered less readily at the glomerulus than their less negatively charged counterparts but were also reabsorbed to a lesser extent by the tubular epithelium.

A Charge-Diffusion-Filtration Model for Endothelial Surface Glycocalyx

Volume 4 ◽  
2004 ◽  
Author(s):  
Bin Chen ◽  
Bingmei Fu
Keyword(s):  
Experimental Data ◽  
Electrical Potential ◽  
Charged Surface ◽  
Endothelial Surface ◽  
Charged Macromolecules ◽  
Microvessel Permeability ◽  
A Charge ◽  
Microvessel Wall ◽  
Good Agreement ◽  
Filtration Model

Endothelial surface glycocalyx plays an important role in the regulation of microvessel permeability by possibly changing its charge and configuration. To investigate the mechanisms of how surface properties of the endothelial cells control the changes in microvessel permeability, we extended the electrodiffusion model developed by Fu et al. (Am. J. Physiol. 284:H1240-1250, 2003), which is for the interendothelial cleft with a negatively charged surface glycocalyx layer, to include the filtration due to hydrostatic and oncotic pressures across the microvessel wall as well as the electrical potential across the glycocalyx layer. On the basis of the hypotheses proposed by Curry (Microcirculation 1(1): 11–26, 1994), the predictions from this electrodiffusion-filtration model provide a remarkably good agreement with experimental data for permeability of negatively charged α-lactalbumin summarized in Curry (Microcirculation 1(1): 11–26, 1994) under various conditions. In addition, we applied this new model to describe the transport of negatively charged macromolecules, bovine serum albumin (BSA), across venular microvessels in frog mesentery. A very interesting prediction is that the convective component of albumin transport is greatly diminished by the presence of a negatively charged glycocalyx under both normal and increased permeability conditions.

Glomerulopathy does not increase renal susceptibility to acute ischemic injury

1984 ◽  
Vol 246 (3) ◽  
pp. F272-F281 ◽  
Author(s):  
R. A. Zager ◽  
L. A. Baltes ◽  
H. M. Sharma ◽  
W. G. Couser
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Nephrotic Syndrome ◽  
Renal Injury ◽  
Artery Occlusion ◽  
Minimal Change ◽  
Glomerular Injury ◽  
Bilateral Renal Artery ◽  
Foot Process ◽  
Ischemic Renal Injury

To determine whether preexistent glomerular injury and the nephrotic syndrome increase renal susceptibility to ischemic renal injury, normal rats and rats with either experimental minimal-change disease (Adriamycin nephropathy) (AN) or membranous nephropathy (passive Heymann nephritis) (PHN) underwent renal functional and histologic studies under either basal conditions or 18 h after bilateral renal artery occlusion (over 30 min). Prior to renal ischemia AN and PHN rats had minimally depressed glomerular filtration rate (GFR), normal (AN) or increased (PHN) renal blood flow (RBF), heavy proteinuria, hypoalbuminemia, decreased urine sodium excretion, extensive glomerular foot process fusion, and intratubular hyalin cast formation. Losses of GFR in response to ischemia were comparable among the three groups of rats (controls, 0.29; AN, 0.28; PHN, 0.25 ml X min-1 X 100 g body wt-1) despite prevailing differences in postischemic hemodynamics. Neither light nor transmission electron microscopy showed any differences in the degree of ischemic renal injury. These results suggest that 1) glomerulopathy and the nephrotic syndrome do not significantly increase renal susceptibility to ischemic renal injury; 2) the syndrome of acute renal failure that occurs in patients with minimal-change glomerulopathy is not due to a marked susceptibility of these kidneys to clinically occult ischemic events; and 3) foot process fusion is probably not a pathophysiologically significant lesion in ischemic acute renal failure, as previously suggested.

scholarly journals The potential roles of NAD(P)H:quinone oxidoreductase 1 in the development of diabetic nephropathy and actin polymerization

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sung-Je Moon ◽  
Jin Young Jeong ◽  
Jae-Hoon Kim ◽  
Dong-Hee Choi ◽  
Hyunsu Choi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Actin Polymerization ◽  
Major Complication ◽  
Glomerular Injury ◽  
Normal Range ◽  
Actin Reorganization ◽  
Nitrogen Levels ◽  
Urine Albumin ◽  
Foot Process

Abstract Diabetic nephropathy (DN) is a major complication of diabetes mellitus. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that has been involved in the progression of several kidney injuries. However, the roles of NQO1 in DN are still unclear. We investigated the effects of NQO1 deficiency in streptozotocin (STZ)-induced DN mice. NQO1 was upregulated in the glomerulus and podocytes under hyperglycemic conditions. NQO1 knockout (NKO) mice showed more severe changes in blood glucose and body weight than WT mice after STZ treatment. Furthermore, STZ-mediated pathological parameters including glomerular injury, blood urea nitrogen levels, and foot process width were more severe in NKO mice than WT mice. Importantly, urine albumin-to-creatinine ratio (ACR) was higher in healthy, non-treated NKO mice than WT mice. ACR response to STZ or LPS was dramatically increased in the urine of NKO mice compared to vehicle controls, while it maintained a normal range following treatment of WT mice. More importantly, we found that NQO1 can stimulate actin polymerization in an in vitro biochemical assay without directly the accumulation on F-actin. In summary, NQO1 has an important role against the development of DN pathogenesis and is a novel contributor in actin reorganization via stimulating actin polymerization.

Charge-Affected Transperitoneal Movement of Amino Acids in Capd

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 88-90 ◽  
Author(s):  
Toshiyuki Nakao ◽  
Makoto Ogura ◽  
Hajime Takahashi ◽  
Tomonari Okada
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Dwell Time ◽  
Plasma Concentrations ◽  
University Hospital ◽  
Blood Samples ◽  
Significant Difference ◽  
Molecular Charge ◽  
Solute Movement ◽  
Positively Charged

Our objective was to investigate the influence of molecular charge on transperitoneal solute movement in continuous ambulatory peritoneal dialysis (CAPD). Tests of peritoneal equilibration were performed. Two liters of 2.27% or 2.5% glucose CAPD dialysate were infused and the dialysate samples were taken after 2 hr and 4 hr, and blood samples were obtained after 4-hr dwell time. Dialysate-to-plasma concentrations ratios (DIP) were calculated for creatinine (Cr) and three amino acids with almost the same molecular weight but quite different charges: glutamic acids (Glu: negatively charged), glutamine (Gin: near neutrally charged), and lysine (Lys: positively charged). The setting was a university hospital. There were 23 stable CAPD patients with a mean age of 56.5±9.5 years and a mean CAPD duration of 15.2±19.4 months. DIP ratio of Glu was much lower than those of Gin, Lys and Cr at both 2 hr and 4 hr (p < 0.01), and DIP of Lys was significantly lower than that of Gin (p < 0.01). There was no significant difference of DIP between Gin and Cr. The order of transperitoneal mobility among the three amino acids was Gin > Lys > Glu. Transperitoneal movement of solutes in CAPD is influenced by molecular charge, the movement of negatively charged solutes is most remarkably retarded in cases of amino acids.

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