Glucose-based dialysis fluids inhibit innate defense against Staphylococcus aureus

Abstract

Background: Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations. Since most commonly used peritoneal dialysis (PD) fluids are glucose-based, we hypothesized that glucose-based PD fluids likely inhibit complement host defenses against S. aureus.

Methods: Commercially available PD fluids were tested: glucose-based (Dianeal), Dianeal supplemented with amino acids, icodextrin-based (Extraneal) and amino acid-based (Nutrineal). Control PD fluid was generated to simulate Dianeal excluding the glucose. Three commercially available glucose concentrations were tested: Dianeal 1.5% (15 gm/1000 ml), Dianeal 2.5% (25 gm/1000 ml) and Dianeal 4.25% (42.5 gm/1000 ml). Complement effectors against S. aureus were analyzed including opsonization with C3-fragments, anaphylatoxin generation, and phagocytosis efficiency. We also evaluated clinical strains, including MRSA strains, and specific complement activation pathways.

Results: Glucose-based PD fluids inhibited complement opsonization of S. aureus (≥7-fold reduction) and inhibited S. aureus-induced generation of anaphylatoxins C3a and C5a (>10-fold reduction) compared to non-glucose based PD fluids. Dianeal 1.5%, 2.5% and 4.25%, all similarly inhibited C3-mediated opsonization. Glucose-based PD fluids showed a ≥4-fold reduction in opsonization of clinical strains of S.aureus, including MRSA strains. Decreased opsonization of S.aureus in the glucose-based PD fluid compared with non-glucose based fluids correlated with decreased phagocytosis by neutrophils.

Conclusion: Complement-mediated opsonophagocytosis of S. aureus and anaphylatoxin generation were severely inhibited in glucose-based PD fluids compared with non-glucose-based PD fluids. By inhibiting complement host defenses, glucose-based PD fluids may increase the risk of and severity of S. aureus peritonitis for CPD patients using these fluids.

Keywords: Anaphylatoxins; Complement; Opsonophagocytosis; Peritoneal dialysis; Peritonitis; Staphylococcus aureus.