The Effect of Dialysate Glucose on Phagocyte Superoxide Generation in Capd Patients

Abstract

In the present study, we investigated the influence of dialysate glucose on superoxide (O2-) generation by peripheral and peritoneal phagocytes in continuous ambulatory peritoneal dialysis (CAPD) patients. Peripheral polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), and peritoneal cells were isolated from peripheral blood and peritoneal effluents, respectively, and their oxidative metabolism was assessed by measuring O2- generation after stimulation with a soluble stimulant [phorbol myristate acetate (PMA), 1 mg/mL, Sigma Chemical, St. Louis, MO, U.S.A.] using the chemiluminescence method. Dialysate glucose effect on O2- generation was also studied in vitro by exposing peripheral PMNL and MNL from healthy controls to peritoneal dialysis fluid (PDF) containing glucose or amino acids at a neutral pH for different time periods. The amount of O2- generation by both peripheral and peritoneal phagocytes in CAPD patients was significantly higher than that in the control, and the response was greater in patients who were dialyzed with high glucose dialysate than those using low glucose dialysate. In an in vitro study, all incubated cells, except the control, showed suppression of O2- generation in the early dwell time (2 hr), and subsequently showed increased responses (peaking at 6 hr), although lower in degree than those observed in vivo. In contrast, amino acid-based PDF exhibited no such effect on O2- generation at identical pH with similar or lower osmolality. Furthermore, the respective increased or decreased oxidative responses with the increased or decreased PDF glucose concentrations in the same patient confirmed the positive effect of PDF glucose on phagocyte O2- generation. It is suggested that increased O2- generation by peritoneal and circulating phagocytes in CAPD patients is at least partly due to the enhancement of hexose monophosphate shunt activity by increasing glucose metabolism in phagocytes, and the increased O2- generation might be involved in long-term complications of CAPD. Therefore, a suitable alternative osmotic agent is needed to provide a more physiological environment to minimize the adverse effects of glucose on cell functions.