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1 Nephrology, University Hospital of Lund, Lund, Sweden
2 Medicine, University Hospital of Lund, Lund, Sweden
* To whom correspondence should be addressed. E-mail: bengt.rippe{at}med.lu.se.
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 ~20mM for 3 weeks or 9 weeks, 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 by 51Cr-EDTA and 125iodohippurate, respectively. In a separate set of animals, diabetic for 9 weeks, and in controls, glomerular sieving coefficients (
) for neutral FITC-Ficoll (mol. radius 1.5-9.0 nm) were assessed using size exclusion chromatography. At 3 weeks of diabetes Cl-HSA and Cl-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 weeks of diabetes duration there was a 2-fold increase of Cl-HSA, while 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 two-fold. In addition a small reduction in proximal tubular reabsorption was observed at 3 weeks, which was further reduced at 9 weeks. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 weeks of STZ-induced diabetes, whereas at 9 weeks there was a decrease in size selectivity owing to an increased number of large glomerular pores.
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