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

Size and charge selectivity of the glomerular filter in early experimental diabetes in rats 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 ∼20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (Cl-HSA) and neutralized albumin (Cl-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using 51 Cr-EDTA and 125 Iiodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (θ) for neutral FITC-Ficoll (molecular radius: 15–90 Å) were assessed using size exclusion chromatography. At 3 wk of diabetes, Cl-HSA and Cl-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 Cl-HSA, whereas Cl-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 Cl-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. sieving coefficient; proteinuria; capillary permeability; fractional clearance; macromolecules; diabetic nephropathy Address for reprint requests and other correspondence: B. Rippe, Dept. of Nephrology, Univ. Hospital of Lund, S-211 85 Lund, Sweden (e-mail: bengt.rippe@med.lu.se ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Renal Physiology The American Physiological Society

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

AJP - Renal Physiology , Volume 293 (5): F1533 – Nov 1, 2007

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References (42)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6127
eISSN
1522-1466
DOI
10.1152/ajprenal.00271.2007
pmid
17699552
Publisher site
See Article on Publisher Site

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 ∼20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (Cl-HSA) and neutralized albumin (Cl-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using 51 Cr-EDTA and 125 Iiodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (θ) for neutral FITC-Ficoll (molecular radius: 15–90 Å) were assessed using size exclusion chromatography. At 3 wk of diabetes, Cl-HSA and Cl-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 Cl-HSA, whereas Cl-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 Cl-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. sieving coefficient; proteinuria; capillary permeability; fractional clearance; macromolecules; diabetic nephropathy Address for reprint requests and other correspondence: B. Rippe, Dept. of Nephrology, Univ. Hospital of Lund, S-211 85 Lund, Sweden (e-mail: bengt.rippe@med.lu.se )

Journal

AJP - Renal PhysiologyThe American Physiological Society

Published: Nov 1, 2007

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