SIZE-SELECTIVITY OF THE GLOMERULAR BARRIER TO HIGH-MOLECULAR-WEIGHT PROTEINS - UPPER SIZE LIMITATIONS OF SHUNT PATHWAYS

To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous protei ns were assessed in normal and in nephrotic Wistar rats in which proxi mal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 Angstrom (beta(2)-microglobulin) t o 90 Angstrom (alpha(2)-macroglobulin). The nephrotic syndrome was ind uced by puromycin aminonucleoside (PAN). A marked restriction of the t ransport of large proteins across the glomerular capillary wall was fo und, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of ra dius 110 to 115 Angstrom accounting for the clearance of large protein s into the primary urine. This protein excretion pattern was almost th e same for control and nephrotic rats, except that in the latter, the number of large pores was increased 170 times. The ratio between the n umber of large and small pores was calculated to be approximate to 7.1 0(-7) in normal rats and to 1.3.10(-4) in PAN nephrotic rats, assuming no classic shunt pathways. If classic shunt pathways had still existe d, they would normally contribute to no more than approximate to 10(-5 ) of the total glomerular filtration rate. We postulate that very larg e macromolecules like IgM will not pass the glomerular filter at all u nder normal conditions, whereas the urine concentration of alpha(2)-ma croglobulin will normally be extremely low.