title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: Parvathi.kumar@chkd.org.
authors.forename: Parvathi S
authors.initials: PS
authors.lastname: Kumar
authors.affiliation: 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: Clifford.Mauriello@SanfordHealth.org.
authors.forename: Clifford T
authors.initials: CT
authors.lastname: Mauriello
authors.affiliation: 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: hairps@evms.edu.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hair
authors.affiliation: 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: Nicholas.rister@chkd.org.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Rister
authors.affiliation: 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: mslawrence@gmail.com.
authors.forename: Courtney
authors.initials: C
authors.lastname: Lawrence
authors.affiliation: 601Children's lane Division of Nephrology, Children's Hospital of The King's Daughters, Norfolk, VA 23507, USA. Electronic address: reem.raafat@chkd.org.
authors.forename: Reem H
authors.initials: RH
authors.lastname: Raafat
authors.affiliation: 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA; 601Children's lane, Division of Infectious diseases, Children's Hospital of The King's Daughters, Norfolk, VA 23507, USA. Electronic address: cunniokm@evms.edu.
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
mesh_terms: D000706:Anaphylatoxins / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000187:drug effects; D015314:Dialysis Solutions / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D006435:Renal Dialysis; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology*
chemical_list: D000706:Anaphylatoxins; D003176:Complement C3; D015314:Dialysis Solutions; D009895:Opsonin Proteins; D005947:Glucose
keywords: Anaphylatoxins; Complement; Opsonophagocytosis; Peritoneal dialysis; Peritonitis; Staphylococcus aureus