Abstract
Objective: The renal fractional clearance of [3H]DEAE dextran has been widely used to substantiate the charge selective model for renal permselectively, although there has only been one reported study on this type of clearance. This study sets out to examine the fractional clearance and glomerular processing of DEAE dextran.
Methods: Fractional clearance studies were performed using isolated perfused rat kidneys. The glomerular processing of DEAE dextran was assessed by examining the kinetics of DEAE dextran uptake in glomerluli isolated post perfusion.
Results: The fractional clearance of DEAE dextran used in the concentration range of 15–150 μg/ml in the perfusate of the isolated perfused kidney did not produce the classical in vivo facilitated transport of DEAE dextran as compared to dextran as observed by Bohrer et al. The fractional clearance curve displays retarded clearance of low molecular weight (small radii) DEAE dextran, giving the appearance of a ‘flat curve’. Similar results were obtained when an oxygen free radical scavenger cocktail was included in the perfusate. These results may be due to the fact that DEAE dextran binds to the glomeruli (at an order of magnitude greater than dextran sulfate). Perfused kidneys with [3H]DEAE dextran for 1 h followed by a five minute perfusion with unlabelled DEAE dextran revealed no significant change in the glomerular levels of [3H]DEAE dextran (unlike dextran sulfate). Perfusion of rat kidneys with 15 μg/ml DEAE dextran produced no changes in the electron microscopical morphology of the glomerulus and no changes in the fractional clearance of dextran.
Conclusions: These results do not support the glomerular charge selectivity model that involves a non-binding electrostatic interaction of the charged dextran with the fixed anion charges of the glomerular capillary wall.