Glomerular sieving of three neutral polysaccharides, polyethylene oxide and bikunin in rat. Effects of molecular size and conformation

Asgeirsson, Daniel; Venturoli, Daniele; Fries, Erik; Rippe, Bengt; Rippe, Catarina

doi:10.1111/j.1748-1716.2007.01733.x

Cited by 53 publications

(71 citation statements)

References 57 publications

(164 reference statements)

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“…2, 6 A GSC of 0.03 would be expected based purely on the size selectivity of a 36 Å radius spherical molecule, such as albumin or Ficoll. 7 The two photon microscopy method has been associated with technical issues, with some reports of albumin GSC values <0.0006. 8,9 These have been resolved by testing various background settings on the microscope.…”

Section: Wayne D Compermentioning

confidence: 99%

“…Equivalent levels of fluorescence can be measured with the genuine filtration of dextran (150,000 kDa), which has a GSC of 0.004 10 as expected from whole animal fractional clearance studies. 7 When using two photon microscopy, molecular trans port probes, such as dextrans and Ficolls, of known GSC should, therefore, always be used as standards when measuring albumin GSC. 13 The capacity of the albumin retrieval pathway is so high (~200 g per day) 2 that any malfunction associated with it will result in hypoalbuminaemia.…”

Section: Wayne D Compermentioning

confidence: 99%

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Albuminuria is controlled primarily by proximal tubules

Comper¹

2014

Nat Rev Nephrol

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Section: Wayne D Compermentioning

confidence: 99%

Section: Wayne D Compermentioning

confidence: 99%

Albuminuria is controlled primarily by proximal tubules

Comper¹

2014

Nat Rev Nephrol

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“…These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability 5 .…”

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confidence: 99%

Quantifying Glomerular Permeability of Fluorescent Macromolecules Using 2-Photon Microscopy in Munich Wistar Rats

Sandoval

Molitoris

2013

JoVE

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Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC) 1,2,3 .Previous techniques used to study renal filtration and establishing the characteristic of the filtration barrier involved micropuncture of the lumen of these early tubular segments with sampling of the fluid content and analysis 4 . These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability 5 .Herein is a detailed outline of the technique used to directly visualize and quantify glomerular fluorescent albumin permeability in vivo. This method allows for detection of filtered albumin across the filtration barrier into Bowman's space (the initial chamber of urinary filtration); and also allows quantification of albumin reabsorption by proximal tubules and visualization of subsequent albumin transcytosis 6 . The absence of fluorescent albumin along later tubular segments en route to the bladder highlights the efficiency of the retrieval pathway in the earlier proximal tubule segments. Moreover, when this technique was applied to determine permeability of dextrans having a similar size to albumin virtually identical permeability values were reported 2 . These observations directly support the need to expand the focus of many proteinuric renal diseases to included alterations in proximal tubule cell reclamation.

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“…In addition, it has been shown that polysaccharides (cf. dextran) exhibit a flexible molecular conformation, making them hyperpermeable compared to more rigid solutes, such as proteins (5,6). 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).…”

mentioning

confidence: 99%

“…dextran) exhibit a flexible molecular conformation, making them hyperpermeable compared to more rigid solutes, such as proteins (5,6). 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).…”

mentioning

confidence: 99%