GLOMERULAR CHARGE SELECTIVITY FOR PROTEINS LARGER THAN SERUM-ALBUMIN AS REVEALED BY LACTATE-DEHYDROGENASE ISOFORMS

it is well known that macromolecules like albumin are markedly restric ted in their passage across the glomerular capillary wall. However, th e relative importance of solute size, charge and shape is currently de bated since much of the previous work is based on dextran in neutral o r charge-modified forms. These polymers have certain drawbacks that ma ke them less suitable for analysis of capillary permeability and the n otion of a glomerular charge barrier has therefore been questioned. Mo reover, macromolecules larger than albumin (mol. wt. 69 000) have been suggested to pass through nonselective 'shunt' pathways. In order to study glomerular permeability, isolated rat kidneys were perfused with albumin solutions containing trace amounts of two differently radiola belled isoenzymes of lactate dehydrogenase (LDH) at low temperature to inhibit tubular function. The isoenzymes have similar size (mol. wt. 140 000) and shape but differ in charge, one carrying a negative net s urface charge (LDH1, -19) and the other being slightly cationic (LDH5, + 2). The urine and perfusate samples were subjected to high pressure liquid chromatography (HPLC) gel-filtration to allow for measurements of intact LDH. The fractional clearance was 0.11% +/- 0.04% for the a nionic LDH1 and 0.56% +/- 0.07% for LDH5, whereas that for albumin was 0.21% +/- 0.03% at a glomerular filtration rate of 0.11 +/- 0.01 mt m in(-1) g(-1) kidney wet weight. The results were analysed using a homo genously charged membrane model and are compatible with a charge densi ty of 35 mEq L-1, with 95% confidence interval of 26-41 mEq L-1. These findings suggest a significant glomerular charge selectivity for prot eins substantially larger than albumin. The charge density is, however , far less than estimated from dextran studies.