Functional and Metabolic Studies on Red Blood Cell Sodium Transport in Chronic Uremia

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Abstract
Red blood cells from 7 out of 13 patients with chronic uremia were found to have increased intracellular concentrations of sodium associated with a reversible inhibition of ouabain-sensitive Na efflux when incubated in control plasma. Although mean Na-K-ATPase activity of RBC hemoly sates was only moderately decreased (21.8 ± 1.5 vs. 26.5 ± 1.8 nmol Pi/mg protein/h), enzyme kinetics revealed a significant increase in Kmatp values for this enzyme in uremic RBCs (1.01 ± 0.1 vs. 0.58 ± 0.03; p < 0.001) which was closely correlated to serum creatinine concentration (r=0.9034). While aerobic glycolysis was unaltered, an increase in glucose-6-phosphate dehydrogenase activity was observed, i.e. the enzyme initiating the pentose-phosphate cycle. In addition, intracellular ATP concentrations of uremic RBCs were significantly higher than ATP concentrations of control RBCs (2.13 ± 0.22 vs. 1.32 ± 0.06 mmol/l RBC; p < 0.01). These data suggest that high intracellular concentrations of Na and ATP in uremic RBCs partially result from a competitive reversible inhibition of the transport ATPase by uremic toxins.