Persistent inhibition of neutrophil function by glucose based dialysis solutions

Local defense mechanisms play an important role in prevention of peritonitis, a major complication of continuous ambulatory peritoneal dialysis (CAPD) therapy. The authors have shown that hypertonic, lactate containing glucose based dialysis solutions (GBDS) used in CAPD lead to an immediate and complete pH-dependent inhibition of actin polymerization and phagocytosis in polymorphonuclear neutrophils (PMN) in vitro. Earlier studies have shown that the pH of the fluid equilibrates from 5.2 to approximately 6.4 during the first 30 min of intraperitoneal dwell time. Thus, the authors designed the current study to determine whether the inhibition of cytoskeletal function and intracellular acidosis induced by acidic solutions are reversed by this pH adjustment. To this end, actin polymerization, phagocytosis, and intracellular pH were studied in PMN isolated from healthy human donors during a 10 min incubation in commercially available GBDS at pH 5.2 and again after pH adjustment to 6.4. Actin polymerization was assessed by measuring F-actin content using NBD phallacidin staining and fluorescence activated cell scanner analysis. Phagocytosis was assessed using zymosan particles, and intracellular pH was monitored by spectrofluorometry. The impairment of cytoskeletal alterations in cells exposed to GBDS at pH 5.2 was persistent and not fully reversed by adjusting the pH. Likewise, phagocytosis remained markedly inhibited and intracellular pH did not rise after adjustment of pH. Thus, the results demonstrate a persistent cytotoxic effect of CAPD solutions on human phagocytes. The authors think that CAPD solutions must be modified to provide a more physiologic pH environment for proper phagocyte function.