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Size and charge selectivity of the glomerular filter in early experimental diabetes in rats

Rippe, Catarina LU ; Rippe, Anna LU ; Torffvit, Ole LU and Rippe, Bengt LU (2007) In American Journal of Physiology: Renal, Fluid and Electrolyte Physiology 293(5). p.1533-1538
Abstract
Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at similar to 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (C1-HSA) and neutralized albumin (C1-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using Cr-51-EDTA and [ I-125]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving... (More)
Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at similar to 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (C1-HSA) and neutralized albumin (C1-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using Cr-51-EDTA and [ I-125]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (theta) for neutral FITC-Ficoll (molecular radius: 15-90 angstrom) were assessed using size exclusion chromatography. At 3 wk of diabetes, C1-HSA and C1-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of C1-HSA, whereas C1-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and C1-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
macromolecules, proteinuria, sieving coefficient, capillary permeability, clearance, fractional, diabetic nephropathy
in
American Journal of Physiology: Renal, Fluid and Electrolyte Physiology
volume
293
issue
5
pages
1533 - 1538
publisher
American Physiological Society
external identifiers
  • wos:000250548000013
  • scopus:36049006561
ISSN
0363-6127
DOI
10.1152/ajprenal.00271.2007
language
English
LU publication?
yes
id
da635d67-0c6a-452c-bbd6-5a3950169e25 (old id 653283)
date added to LUP
2007-12-14 12:02:47
date last changed
2017-03-26 03:44:26
@article{da635d67-0c6a-452c-bbd6-5a3950169e25,
  abstract     = {Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at similar to 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (C1-HSA) and neutralized albumin (C1-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using Cr-51-EDTA and [ I-125]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (theta) for neutral FITC-Ficoll (molecular radius: 15-90 angstrom) were assessed using size exclusion chromatography. At 3 wk of diabetes, C1-HSA and C1-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of C1-HSA, whereas C1-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and C1-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores.},
  author       = {Rippe, Catarina and Rippe, Anna and Torffvit, Ole and Rippe, Bengt},
  issn         = {0363-6127},
  keyword      = {macromolecules,proteinuria,sieving coefficient,capillary permeability,clearance,fractional,diabetic nephropathy},
  language     = {eng},
  number       = {5},
  pages        = {1533--1538},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Renal, Fluid and Electrolyte Physiology},
  title        = {Size and charge selectivity of the glomerular filter in early experimental diabetes in rats},
  url          = {http://dx.doi.org/10.1152/ajprenal.00271.2007},
  volume       = {293},
  year         = {2007},
}