Objectives Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell. Design Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations. Results Exposure to PD fluid induced activation of IP complement [formation of C3a(desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin–antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration. Conclusions The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.

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A rapid screening method was developed for assessment of the toxic effects of fluid materials on the respiratory burst response of polymorphonuclear neutrophils (PMNLs). The method was used to detect adverse effects of peritoneal dialysis (PD) fluids. Intoxication of the respiratory burst response attenuates the bacterial killing capacity of PMNLs, and increases the sensitivity of patients to peritoneal infection. Capillary blood was taken from healthy donors, placed in drops on commercially available titanium pieces, and incubated in a humidified chamber at 37°C for up to 1 hour. The blood was rinsed off with saline, and the adhering cells were characterised by immunofluorescence by using antibodies directed against specific cell-differentiation antigens. A majority (> 95%) of the adhering leucocytes were PMNLs. The surface expression of selectins was down-regulated after 30 minutes, and the expression of integrins was down-regulated after blood exposure for 1 hour. NADPH-oxidase activity of the adhering cells was stimulated by f-MLP peptide and by opsonised zymosan. The zymosan-induced activation showed a lag-phase after 1 hour, consistent with the down-regulated expression of integrin. The zymosan-stimulated enzyme activity was used as an indicator of the cytotoxicity of PD fluids. NADPH-oxidase activity was inhibited by PD fluids with a pH of 5.7 and by heat-sterilised PD fluids. The results were compared with data obtained by using isolated circulating cells and cells from peritoneal dwell fluid.