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

The effect of shape on the transglomerular passage of solutes has not been hitherto systematically studied. We perfused isolated rat kidneys to determ ine 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) (Angs trom) 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%, respe ctively, on a fivefold increase in GFR. Under the same conditions, theta fo r albumin increased from 0.15 to 0.74%, and similar behavior was observed f or larger Ficolls (a(SE) >45 Angstrom). Pore analysis showed that the "appa rent neutral" solute radii of Ficoll, albumin, bikunin, and hyaluronan were 35, 64, 33, and 24 Angstrom, respectively, despite similar a(SE). In addit ion, the properties of the glomerular filter changed with increasing GFR an d hydrostatic pressure. We conclude that elongated shape, irrespective of s ize and charge, drastically increases the transglomerular passage of a solu te, an effect that is related to its frictional ratio.