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Size-selectivity of the glomerular barrier to high molecular weight proteins: upper size limitations of shunt pathways

Tencer, Jan LU ; Frick, Inga-Maria LU ; Öquist, Björn W; Alm, Per LU and Rippe, Bengt LU (1998) In Kidney International 53(3). p.709-715
Abstract
To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous proteins were assessed in normal and in nephrotic Wistar rats in which proximal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 A (Beta 2-microglobulin) to 90 A (alpha 2-macroglobulin). The nephrotic syndrome was induced by puromycin aminonucleoside (PAN). A marked restriction of the transport of large proteins across the glomerular capillary wall was found, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of radius 110 to 115 A accounting for the clearance of large proteins... (More)
To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous proteins were assessed in normal and in nephrotic Wistar rats in which proximal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 A (Beta 2-microglobulin) to 90 A (alpha 2-macroglobulin). The nephrotic syndrome was induced by puromycin aminonucleoside (PAN). A marked restriction of the transport of large proteins across the glomerular capillary wall was found, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of radius 110 to 115 A accounting for the clearance of large proteins into the primary urine. This protein excretion pattern was almost the same for control and nephrotic rats, except that in the latter, the number of large pores was increased 170 times. The ratio between the number of large and small pores was calculated to be approximately equal to 7 x 10(-7) in normal rats and to 1.2 x 10(-4) in PAN nephrotic rats, assuming no classic shunt pathways. If classic shunt pathways had still existed, they would normally contribute to no more than approximately equal to 10(-5) of the total glomerular filtration rate. We postulate that very large macromolecules like IgM will not pass the glomerular filter at all under normal conditions, whereas the urine concentration of alpha2-macroglobulin will normally be extremely low. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
glomerular capillary filter, size selectivity of glomerular barrier, proteins, shunt pathways, clearance
in
Kidney International
volume
53
issue
3
pages
709 - 715
publisher
Nature Publishing Group
external identifiers
  • pmid:9507218
  • scopus:0031939927
ISSN
1523-1755
DOI
10.1046/j.1523-1755.1998.00797.x
language
English
LU publication?
yes
id
b43a7e8b-58b6-4574-8f12-42598a82a8a7 (old id 1113002)
date added to LUP
2008-07-14 10:29:37
date last changed
2017-04-30 14:27:23
@article{b43a7e8b-58b6-4574-8f12-42598a82a8a7,
  abstract     = {To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous proteins were assessed in normal and in nephrotic Wistar rats in which proximal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 A (Beta 2-microglobulin) to 90 A (alpha 2-macroglobulin). The nephrotic syndrome was induced by puromycin aminonucleoside (PAN). A marked restriction of the transport of large proteins across the glomerular capillary wall was found, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of radius 110 to 115 A accounting for the clearance of large proteins into the primary urine. This protein excretion pattern was almost the same for control and nephrotic rats, except that in the latter, the number of large pores was increased 170 times. The ratio between the number of large and small pores was calculated to be approximately equal to 7 x 10(-7) in normal rats and to 1.2 x 10(-4) in PAN nephrotic rats, assuming no classic shunt pathways. If classic shunt pathways had still existed, they would normally contribute to no more than approximately equal to 10(-5) of the total glomerular filtration rate. We postulate that very large macromolecules like IgM will not pass the glomerular filter at all under normal conditions, whereas the urine concentration of alpha2-macroglobulin will normally be extremely low.},
  author       = {Tencer, Jan and Frick, Inga-Maria and Öquist, Björn W and Alm, Per and Rippe, Bengt},
  issn         = {1523-1755},
  keyword      = {glomerular capillary filter,size selectivity of glomerular barrier,proteins,shunt pathways,clearance},
  language     = {eng},
  number       = {3},
  pages        = {709--715},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Size-selectivity of the glomerular barrier to high molecular weight proteins: upper size limitations of shunt pathways},
  url          = {http://dx.doi.org/10.1046/j.1523-1755.1998.00797.x},
  volume       = {53},
  year         = {1998},
}