Effects of filtration rate on the glomerular barrier and clearance of four differently shaped molecules

The effect of shape on the transglomerular passage of solutes has not been hitherto systematically studied. We perfused isolated rat kidneys to determine the fractional clearances (theta) at various filtration rates for four molecules of different shapes but with similar Stokes-Einstein radii (a(SE) = 34-36 Angstrom). The theta for hyaluronan, bikunin, and Ficoll(36) (Angstrom) were 66, 16, and 11%, respectively, at a glomerular filtration rate (GFR) of 0.07 ml.min(-1).g wet wt(-1) and decreased to 46, 14, and 7%, respectively, on a fivefold increase in GFR. Under the same conditions, theta for albumin increased from 0.15 to 0.74%, and similar behavior was observed for larger Ficolls (a(SE) >45 Angstrom). Pore analysis showed that the "apparent neutral" solute radii of Ficoll, albumin, bikunin, and hyaluronan were 35, 64, 33, and 24 Angstrom, respectively, despite similar a(SE). In addition, the properties of the glomerular filter changed with increasing GFR and hydrostatic pressure. We conclude that elongated shape, irrespective of size and charge, drastically increases the transglomerular passage of a solute, an effect that is related to its frictional ratio.