Alterations of Polymorphonuclear Leukocyte Glycogen Metabolism and Glucose Uptake in Dialysis Patients

Abstract

Human polymorphonuclear leukocytes (PMNs) are activated during extracorporeal circulation. An indicator of PMN activation may be the glycogen-degrading enzyme phosphorylase. It is unknown whether dialysis therapy may influence PMN carbohydrate metabolism. Therefore, PMNs were isolated from healthy control subjects, patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and patients undergoing regular hemodialysis therapy (RDT) before, during, and at the end of hemodialysis (HD) treatment using dialyzers made of polysulfone or polymethylmethacrylate (PMMA). Nifedipine (NIF) was continuously infused during HD with PMMA in 5 patients at a dose of 18 micrograms/kg body weight per hour. Glycogen, activity of glycogen synthetase and phosphorylase (active and inactive forms of both enzymes), and glucose uptake with and without stimulation with the chemotactic peptide FMLP were determined in these PMNs. During HD with PMMA, there was a significant increase of PMN phosphorylase "a" activity 15 and 30 minutes after the start of HD. HD with polysulfone did not stimulate the active "a" form of the glycogen-degrading enzyme in PMNs. HD with PMMA significantly inhibited the active I-form of glycogen synthetase, whereas polysulfone activated glycogen synthetase I. NIF inhibited phosphorylase "a" activation during HD with PMMA. PMN glycogen content and glucose uptake were improved during HD with polysulfone, but not with PMMA. PMN glycogen content, activity of glycogen synthetase, and glucose uptake were significantly lower also in CAPD patients compared with healthy controls. These data show that HD with PMMA activates PMN glycogenolysis. This effect can be inhibited by calcium channel blockers. PMN glycogen content of RDT and CAPD patients is significantly lower compared with healthy controls due to inhibition of glycogen synthesis. Elimination of dialyzable factor(s) improves, but does not restore, PMN glycogen synthesis and glucose uptake.