Persistent inhibition of neutrophil function by glucose based dialysis solutions

Area of Science:

• Nephrology
• Immunology
• Cell Biology

Background:

• Peritonitis is a major complication of continuous ambulatory peritoneal dialysis (CAPD).
• Local defense mechanisms, particularly polymorphonuclear neutrophils (PMN), are crucial for preventing peritonitis.
• Standard glucose-based dialysis solutions (GBDS) have an acidic pH that can affect PMN function.

Purpose of the Study:

• To investigate if the inhibitory effects of acidic CAPD solutions on PMN cytoskeletal function and intracellular pH are reversible upon pH adjustment.
• To assess the impact of commercially available GBDS at pH 5.2 and pH 6.4 on PMN actin polymerization, phagocytosis, and intracellular pH in vitro.

Main Methods:

• Human PMN were isolated and incubated with GBDS at pH 5.2 and pH 6.4.
• Actin polymerization was measured using NBD phallacidin staining and flow cytometry.
• Phagocytosis was assessed using zymosan particles.
• Intracellular pH was monitored using spectrofluorometry.

Main Results:

• Incubation with GBDS at pH 5.2 caused persistent inhibition of actin polymerization and phagocytosis in PMN.
• Adjusting the pH of the GBDS to 6.4 did not fully reverse the inhibition of cytoskeletal function or phagocytosis.
• Intracellular acidosis in PMN was not resolved by pH adjustment of the dialysis solution.

Conclusions:

• Acidic CAPD solutions exert a persistent cytotoxic effect on human phagocytes, impairing essential immune functions.
• Current GBDS formulations may compromise the local defense mechanisms in the peritoneal cavity.
• Modification of CAPD solutions to achieve a more physiologic pH is recommended to support optimal phagocyte function and potentially reduce peritonitis risk.