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Permeability of the glomerular filtration barrier in relation to the size, shape, charge and deformability of the permeating molecules

Asgeirsson, Daniel LU (2009) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2009:28.
Abstract
Characterization of the glomerular filtration barrier is of fundamental importance for understanding the pathophysiology of proteinuric kidney diseases. Furthermore, it can be of key value in the understanding of microalbuminuria, which is often associated with endothelial dysfunction in conjunction with cardiovascular disease. In the four studies of this doctoral thesis, macromolecular probes having different frictional ratios (f/f0) and charge were investigated in order to give deepened insights into the usefulness of polysaccharides as probes of the permselectivity of the glomerular filter for proteins. In Study I, the extensively cross-linked polysaccharide Ficoll, was shown to overestimate the true permeability of the glomerular... (More)
Characterization of the glomerular filtration barrier is of fundamental importance for understanding the pathophysiology of proteinuric kidney diseases. Furthermore, it can be of key value in the understanding of microalbuminuria, which is often associated with endothelial dysfunction in conjunction with cardiovascular disease. In the four studies of this doctoral thesis, macromolecular probes having different frictional ratios (f/f0) and charge were investigated in order to give deepened insights into the usefulness of polysaccharides as probes of the permselectivity of the glomerular filter for proteins. In Study I, the extensively cross-linked polysaccharide Ficoll, was shown to overestimate the true permeability of the glomerular filtration barrier to neutral globular proteins, indicating that size-selectivity is even more important than previously recognized. However, Ficolls in the SE-radius range 55-75Å, were not hyperpermeable across the large pores of the glomerular filter, indicating their usefulness for studying proteinuric diseases. In study II, the results of recent publications, indicating the lack of charge-selectivity in the glomerular filter, were shown to be artifactual. Thus, polysaccharides, when negatively charged, seemed to become expanded and to increase their f/f0, thereby becoming more hyperpermeable. Thus earlier findings, showing that the glomerular filter discriminates proteins based on charge, are still valid. In study III, we showed that the main size-restrictive barrier of the glomerular filter lies, not at the podocyte level, but closer to the plasma compartment, or may be evenly distributed along the thickness of the filter. This was

indicated by the lack of concentration-polarization upon increasing GFR. Study IV demonstrated that the differential permeabilities of polysaccharides and proteins across the glomerular barrier were not observed across the continuous capillary walls of the peritoneal membrane, an enigma that warrants further study. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Tenstad, Olav, University of Bergen, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
proteinuria, capillary physiology, peritoneal membrane, dialysis, microalbuminuria, cardiovascular, endothelial dysfunction, diagnosis
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2009:28
pages
122 pages
publisher
Department of Nephrology, Lund University
defense location
Optimahusets föreläsningssal, Barngatan 2, University Hospital Lund
defense date
2009-04-09 09:00
ISSN
1652-8220
ISBN
978-91-86253-15-8
language
English
LU publication?
yes
id
82a3aeb3-92b7-4830-8e1f-2b8ec7737f31 (old id 1301510)
date added to LUP
2009-02-27 09:56:27
date last changed
2016-09-19 08:44:51
@phdthesis{82a3aeb3-92b7-4830-8e1f-2b8ec7737f31,
  abstract     = {Characterization of the glomerular filtration barrier is of fundamental importance for understanding the pathophysiology of proteinuric kidney diseases. Furthermore, it can be of key value in the understanding of microalbuminuria, which is often associated with endothelial dysfunction in conjunction with cardiovascular disease. In the four studies of this doctoral thesis, macromolecular probes having different frictional ratios (f/f0) and charge were investigated in order to give deepened insights into the usefulness of polysaccharides as probes of the permselectivity of the glomerular filter for proteins. In Study I, the extensively cross-linked polysaccharide Ficoll, was shown to overestimate the true permeability of the glomerular filtration barrier to neutral globular proteins, indicating that size-selectivity is even more important than previously recognized. However, Ficolls in the SE-radius range 55-75Å, were not hyperpermeable across the large pores of the glomerular filter, indicating their usefulness for studying proteinuric diseases. In study II, the results of recent publications, indicating the lack of charge-selectivity in the glomerular filter, were shown to be artifactual. Thus, polysaccharides, when negatively charged, seemed to become expanded and to increase their f/f0, thereby becoming more hyperpermeable. Thus earlier findings, showing that the glomerular filter discriminates proteins based on charge, are still valid. In study III, we showed that the main size-restrictive barrier of the glomerular filter lies, not at the podocyte level, but closer to the plasma compartment, or may be evenly distributed along the thickness of the filter. This was<br/><br>
indicated by the lack of concentration-polarization upon increasing GFR. Study IV demonstrated that the differential permeabilities of polysaccharides and proteins across the glomerular barrier were not observed across the continuous capillary walls of the peritoneal membrane, an enigma that warrants further study.},
  author       = {Asgeirsson, Daniel},
  isbn         = {978-91-86253-15-8},
  issn         = {1652-8220},
  keyword      = {proteinuria,capillary physiology,peritoneal membrane,dialysis,microalbuminuria,cardiovascular,endothelial dysfunction,diagnosis},
  language     = {eng},
  pages        = {122},
  publisher    = {Department of Nephrology, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Permeability of the glomerular filtration barrier in relation to the size, shape, charge and deformability of the permeating molecules},
  volume       = {2009:28},
  year         = {2009},
}