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

Background. The purported existence of "large pores" in the glomerular capi llary wall has been derived primarily from studies using dextrans and Ficol ls. Systematic studies using high molecular weight proteins have not been p erformed. One of the difficulties is that recent studies have demonstrated that albumin and other proteins undergo degradation during renal passage. O ur study took into account this renal degradation in measuring the fraction al clearance of various high molecular weight proteins (the hydrodynamic ra dii range was between 48 to 70 Angstrom). Methods. Fractional clearances of tritium-labeled proteins were measured us ing ALZET osmotic pumps, which are designed to release a slow continuous in fusion of tracer. Blood and urine collections were taken at 24-hour interva ls over seven days and were counted for radioactivity, and glomerular filtr ation rate was measured by a creatinine assay. Results. Steady-state levels of [H-3]protein in plasma were obtained by day 6. The [H-3]proteins in the plasma showed no degradation. The fractional c learances (mean +/- SD, N = 5) of the various proteins were albumin (radius = 36 Angstrom; 0.0023 +/- 0.0009), transferrin (48 Angstrom; 0.0046 +/- 0. 0007), lactoperoxidase (58 Angstrom; 0.0045 +/- 0.0005), immunoglobulin G ( 62 Angstrom; 0.0043 +/- 0.0009),lactate dehydrogenase (64 Angstrom; 0.0041 +/- 0.0009), and glucose oxidase (70 Angstrom; 0.0036 +/- 0.0011). Conclusions. These values suggest a weak dependence of fractional clearance on size-selective filtration, except for albumin, which undergoes a specif ic type of postglomerular processing. The fractional clearances were higher than expected from previous data on dextrans and Ficolls of equivalent hyd rodynamic radius, and thus demonstrate that "large pores" may already exist in normal glomerular capillary walls.