Effects of glomerular filtration rate on Ficoll sieving coefficients (θ) in rats

The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients (θ) to neutral fluorescein isothiocyanate (FITC)-Ficoll 70/400 obtained at low (hydropenic) vs raised (normal) glomerular filtration rates (GFRs). The θ for FITC-Ficoll was determined in anesthetized Wistar rats (304±18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.2±0.16 ml/min (±s.e.), assessed using the plasma to urine clearance of FITC-inulin and 51Cr-ethylenediaminetetraacetic acid. FITC-Ficoll 70/400 was infused intravenously (i.v.) following an initial bolus dose. To raise GFR, to an average of ∼2 ml/min, 5 ml of serum together with glucagon (3 μg/min) was given i.v. FITC-inulin and FITC-Ficoll were determined in plasma and urine using size-exclusion high-performance liquid chromatography. The θ for Ficoll as a function of Stokes–Einstein radius was significantly reduced in the range of 13–43 Å when GFR was raised. The maximal θ lowering effect, in relative terms, of raising GFR was obtained for a Ficoll ae of ∼32 Å. For Ficoll36 Å (cf. albumin), θ was reduced from 0.111±0.009 to 0.081±0.012 (P<0.05; n=7) for the GFR increment imposed. The reduction in θ for Ficoll after raising GFR indicates the presence of a high diffusive component of glomerular Ficoll filtration in rats in vivo and contradicts the notion of a significant concentration polarization effect in the glomerular filter upon Ficoll molecules <50 Å in radius.