Inhibition of transepithelial sodium transport in the frog skin by a low molecular weight fraction of uremic serum

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Abstract
An inhibitor of transepithelial sodium transport was found in a low molecular weight fraction obtained from serum of patients with far advanced chronic renal disease. In 18 nondialyzed patients, the mean inhibition of short circuit current (SCC) was 24.9 ±2.2% (SE). With a comparable fraction from 11 normal subjects. SCC decreased by only 5.3 ±1.5%. There was significantly greater inhibition with the serum fractions of patients with end stage renal disease being maintained on chronic hemodialysis than in the normal control group; but the degree of inhibition in the dialyzed population was significantly less than that observed in the nondialyzed chronically uremic patients. The inhibition of SCC produced by the serum fractions of a group of seven patients with acute renal failure was not significantly different from the control group despite the presence of high grade uremia in the former. The inhibitory fraction has characteristics identical with the uremic serum fraction which previously has been shown to inhibit p-aminohippurate (PAH) uptake by rabbit kidney cortical slices. With gel filtration through Sephadex G-25, the active fraction appears after the major peaks of substances as small as urea and sodium; hence it may have been retarded on the column. But its ultrafiltration characteristics suggest that its molecular weight may be less than 1000. The inhibitory capability was not destroyed by boiling, freezing, or digestion with chymotrypsin or pronase. Neither methylguanidine nor guanidinosuccinic acid in concentrations well above those present in the serum of uremic patients inhibited sodium transport in the frog skin. The data suggest that there is an inhibitor of sodium transport in the serum of patients with chronic uremia. The role of this material in the regulation of sodium excretion in uremia as well as its possible role as a uremic toxin are subjects of both theoretical and practical interest.