High glomerular permeability of bikunin despite similarity in charge and hydrodynamic size to serum albumin

Abstract

Bikunin is a chondroitin-sulphate containing serum protein with a Stokes-Einstein radius and a negative net charge close to those of serum albumin. The plasma half life of bikunin is about 10 minutes, and approximately half of its clearance occurs in the kidneys. The quantitative role of glomerular filtration in the renal clearance of this protein has not been determined. To assess the glomerular permeability of bikunin we used isolated rat kidneys that were perfused with an albumin solution. The metabolic activities of the tubuli were inhibited by low temperature (8 degrees C). The clearances of radiolabeled bikunin and albumin were repeatedly determined under identical conditions. The fractional clearance of bikunin was found to be 80 times higher than that of albumin: 15% +/- 1% versus 0.18% +/- 0.02%. This value for bikunin can fully account for its renal clearance in vivo. It has previously been shown that uncharged flexible solutes, such as dextrans, have higher renal clearances than globular molecules with similar radii. The high glomerular permeability of bikunin is therefore probably due to its elongated and flexible configuration. Moreover, the observed clearance value of the anionic molecule bikunin is close to that of a neutral flexible dextran of similar size, indicating that the charge of bikunin is of little importance for its glomerular permeability.