Charge selectivity in kidney ultrafiltration is associated with glomerular uptake of transport probes

The isolated perfused kidney exhibits substantial charge selectivity, as in vivo, in relation to fractional clearance of [3H]dextran sulfate and [3H]dextran. When cycloheximide is present in perfusate, fractional clearance of dextran sulfate is increased and proteinuria becomes significant, but glomerular filtration rate remains essentially unchanged compared with control. The possible role of cells in affecting transglomerular transport was demonstrated when isolated glomeruli from control perfused kidneys showed a very significant resident concentration of [3H]dextran sulfate and [3H]albumin, whereas there was no corresponding accumulation of [3H]dextran or [3H]inulin. Glomerular concentration of dextran sulfate and albumin was significantly reduced by cycloheximide. Kinetics of uptake and release of glomerular dextran sulfate indicated that it had a half-life of glomerular residence of approximately 2-3 min and that this half-life was considerably extended in the presence of cycloheximide. The half-life for glomerular residence of albumin was in the range of 30-40 min. The conclusion from this work is that glomerular charge selectivity for dextran sulfate could be quantitatively rationalized on the basis of transient uptake and release by glomerular cells.