Fractional clearance of high molecular weight proteins in conscious rats using a continuous infusion method

Fractional clearance of high molecular weight proteins in conscious rats using a continuous-infusion method. The purported existence of “large pores” in the glomerular capillary wall has been derived primarily from studies using dextrans and Ficolls. Systematic studies using high molecular weight proteins have not been performed. One of the difficulties is that recent studies have demonstrated that albumin and other proteins undergo degradation during renal passage. Our study took into account this renal degradation in measuring the fractional clearance of various high molecular weight proteins (the hydrodynamic radii range was between 48 to 70 Å). Fractional clearances of tritium-labeled proteins were measured using ALZET osmotic pumps, which are designed to release a slow continuous infusion of tracer. Blood and urine collections were taken at 24-hour intervals over seven days and were counted for radioactivity, and glomerular filtration rate was measured by a creatinine assay. Steady-state levels of [3H]protein in plasma were obtained by day 6. The [3H]proteins in the plasma showed no degradation. The fractional clearances (mean ± SD, N = 5) of the various proteins were albumin (radius = 36 Å; 0.0023 ± 0.0009), transferrin (48 Å; 0.0046 ± 0.0007), lactoperoxidase (58 Å; 0.0045 ± 0.0005), immunoglobulin G (62 Å; 0.0043 ± 0.0009), lactate dehydrogenase (64 Å; 0.0041 ± 0.0009), and glucose oxidase (70 Å; 0.0036 ± 0.0011). These values suggest a weak dependence of fractional clearance on size-selective filtration, except for albumin, which undergoes a specific type of postglomerular processing. The fractional clearances were higher than expected from previous data on dextrans and Ficolls of equivalent hydrodynamic radius, and thus demonstrate that “large pores” may already exist in normal glomerular capillary walls.