Abnormal Red Cell Metabolism in Patients With Chronic Uremia: Nature of the Defect and Its Persistence Despite Adequate Hemodialysis

Abstract

A red cell metabolic abnormality, which diminishes the maximum activity of the pentose phosphate shunt, occurs in some uremic patients, even those adequately dialyzed with fluids prepared from distilled or charcoal-filtered water. Within individual patients the severity of this abnormality does not change even after 9 mo of consecutive hemodialyses. However, between patients it does correlate inversely with hematocrit. When erythrocytes from patients with the abnormality are stressed with oxidant compounds, such as ascorbate, erythrocyte glucose consumption and lactate formation are abnormally increased, while lactate/pyruvate ratios abnormally diminish. Concomitantly, red cell glycolytic intermediates, including fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, and pyruvate, markedly accumulate. Surprisingly, no increase of 2-phosphoglycerate occurs, which suggests that inefficient phosphoglyceromutase activity underlies this perturbation of erythrocyte metabolism and its associated hemolytic process.