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1 Laboratory of Immunopathology, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
2 Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria, Australia
* To whom correspondence should be addressed. E-mail: wayne.comper{at}med.monash.edu.au.
Recent studies, using low temperature perfusion of rat kidneys, have claimed the existence of renal charge selectivity simply on the basis of the differential excretion rates of uncharged Ficoll and charged proteins. In order to test for the existence of charge selectivity in vivo, we have examined the clearance of negatively charged Ficoll as compared to uncharged Ficoll. A short term approach to steady state was used to study the fractional clearances. Relative clearances were also examined using an osmotic pump technique where the tracers reach a steady state value in conscious rats after seven days. The carboxymethyl Ficoll was stable during filtration and renal passage, was not taken up by the kidneys and did not bind to plasma proteins. There was no significant difference in the fractional clearance of molecules with radius of 36 A for Ficoll (fractional clearance = 0.048 ± 0.038, n = 5) and negatively charged carboxymethyl Ficoll (fractional clearance = 0.028 ± 0.019, n = 5). For molecules with radii greater than 36 A, the carboxymethyl Ficoll had facilitated clearance with respect to uncharged Ficoll (for example, at a radius of 60 A fractional clearance for Ficoll = 0.0012 ± 0.0005 (n = 5). Whereas for carboxymethyl Ficoll = 0.015 ± 0.005 (n = 5)). Renal function was not compromised by carboxymethyl Ficoll as uncharged Ficoll exhibited similar hydrodynamic size profiles when studied in the presence of excess unlabeled carboxymethyl Ficoll. The facilitated clearance of negatively charged Ficoll with respect to uncharged Ficoll reveals a property of the capillary wall, which has been previously observed with other non-proteinaceous polyanions. This study demonstrates that the glomerular capillary wall is not charge selective in the form of excluding negatively charged Ficoll. However, the charge properties of the capillary wall may influence the facilitated transport of charged Ficoll as compared to uncharged Ficoll.
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