title: Continuous dialysis with bicarbonate/lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function.
abstract: To circumvent the potentially negative consequences of long-term exposure to unphysiologic acidic lactate-buffered peritoneal dialysis fluids (PDF), neutral pH solutions buffered with bicarbonate/lactate have recently been introduced in phase 2 and 3 clinical trials. This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF. Before the study, during the run in period of a phase 3 clinical trial, all patients had been taking LPD for at least the previous 18 wk. At the beginning of the study (day 0), both constitutive and serum-treated zymosan (STZ) stimulated tumor necrosis factor alpha (TNF-alpha) synthesis were assessed in PMØ isolated from 12-h dwell effluent (with 1.36% glucose) in all patients. The patients were subsequently randomized to either continuous TBL or LPD therapy and PMØ function was assessed after further 3- and 6-mo periods in all patients. At all time points measured STZ induced a dose-dependent increase in PMØ TNF-alpha secretion (P = 0.043 versus control for doses greater than 100 microg/ml). In patients continuously dialyzed with LPD, constitutive PMØ TNF-alpha synthesis levels (mean +/- SEM, pg/10(6) PMØ per18 h, n = 5 patients) were 154 +/- 65, 261 +/- 60, and 101 +/- 99 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 microg/ml) levels were 1340 +/- 519, 1046 +/- 586, and 758 +/- 250 at 0, 3, and 6 mo, respectively. In patients dialyzed with TBL, constitutive PMØ TNF-alpha synthesis levels (pg/10(6) PMØ per 18 h, n = 5 patients) were 300 +/- 136, 106 +/- 35, and 213 +/- 62 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 microg/ml) levels were 1969 +/- 751, 1541 +/- 330, and 2670 +/- 671 at 0, 3, and 6 mo, respectively. At 6 mo, STZ-stimulated PMØ TNF-alpha synthesis was significantly higher in patients treated with TBL compared with those treated with LPD (P = 0.0035). These data suggest that in patients continuously dialyzed with a neutral pH solution, there is a long-term improvement in PMØ function compared with patients on conventional therapy. Better PMØ function suggests improved host defense status and may affect the peritoneum's susceptibility to infection and potentially reduce the negative consequences of repeated intraperitoneal inflammation on long-term membrane function.
authors.affiliation: Institute of Nephrology, University of Wales College of Medicine, Cardiff, Wales, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jones
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Holmes
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Mackenzie
authors.forename: Rachel
authors.initials: R
authors.lastname: Stead
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Coles
authors.forename: John D
authors.initials: JD
authors.lastname: Williams
authors.forename: Dirk
authors.initials: D
authors.lastname: Faict
authors.forename: Nicholas
authors.initials: N
authors.lastname: Topley
mesh_terms: D000368:Aged; D001639:Bicarbonates / Q000008:administration & dosage*; D002021:Buffers; D002452:Cell Count; D015314:Dialysis Solutions; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D020127:Recovery of Function; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D001639:Bicarbonates; D002021:Buffers; D015314:Dialysis Solutions; D004338:Drug Combinations; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D015054:Zymosan