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Continuous Dialysis with Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluids Results in a Long-Term Improvement in Ex Vivo Peritoneal Macrophage Function

Suzanne Jones^*, Clifford J. Holmes, Ruth K. Mackenzie^*, Rachel Stead^*, Gerald A. Coles^*, John D. Williams^*, Dirk Faict and Nicholas Topley^*

*Institute of Nephrology, University of Wales College of Medicine, Cardiff, Wales, United Kingdom; and Baxter Healthcare Renal Division, Nivelles, Belgium, and McGaw Park, Illinois.

Correspondence to Dr. Clifford Holmes, 1620 Waukegan Road, McGaw Park, IL 60085. Phone: 847-473-6352; Fax: 847-473-6902; E-mail: holmesc{at}baxter.com

Abstract

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-) 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- secretion (P = 0.043 versus control for doses greater than 100 µg/ml). In patients continuously dialyzed with LPD, constitutive PMØ TNF- synthesis levels (mean ± SEM, pg/10⁶ PMØ per18 h, n = 5 patients) were 154 ± 65, 261 ± 60, and 101 ± 99 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 µg/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- synthesis levels (pg/10⁶ 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 µg/ml) levels were 1969 ± 751, 1541 ± 330, and 2670 ± 671 at 0, 3, and 6 mo, respectively. At 6 mo, STZ-stimulated PMØ TNF- 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.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673