Biocompatibility and tolerability of a purely bicarbonate-buffered peritoneal dialysis solution.

BACKGROUND: Novel peritoneal dialysis solutions are characterized by a minimal content of glucose degradation products and a neutral pH. Many studies have shown the biocompatibility of neutral lactate-buffered solutions; however, until now, the effect of purely bicarbonate-buffered solutions has not been intensively studied in vivo. METHODS: This study was an open label, prospective, crossover multicenter trial to investigate the biocompatibility of a purely bicarbonate-buffered solution (bicPDF) by measuring biocompatibility parameters such as cancer antigen 125 (CA125) in peritoneal effluent. 55 patients were enrolled in the study. After a 2-week run-in phase, 53 patients could be randomized into 2 groups, starting with either standard lactate-buffered peritoneal dialysis fluid (SPDF) for 12 weeks (phase 1) and then switching to bicPDF for 12 weeks (phase 2), or vice versa. Overnight peritoneal effluents were collected at baseline and at the end of phases 1 and 2 and were tested for CA125, hyaluronic acid, vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interferon gamma (IFNgamma), and transforming growth factor-beta(1) (TGF-beta1). Total ultrafiltration and residual renal function were also assessed. At the end of the study, pain during fluid exchange and dwell was evaluated using special questionnaires. RESULTS: 34 patients completed the study; 27 of them provided data for analysis of the biocompatibility parameters. CA125 levels in overnight effluent were significantly higher with bicPDF (61.9 +/- 33.2 U/L) than with SPDF (18.6 +/- 18.2 U/L, p < 0.001). Hyaluronic acid levels were significantly lower after the use of bicPDF (185.0 +/- 119.6 ng/mL) than after SPDF (257.4 +/- 174.0 ng/mL, p = 0.013). Both TNF-alpha and TGF-beta1 showed higher levels with the use of bicPDF than with SPDF. No differences were observed for IL-6, VEGF, or IFNgamma levels. We observed an improvement in the glomerular filtration rate with the use of bicPDF but no differences were observed for total fluid loss. Pain scores could be analyzed in 23 patients: there was no difference between the solutions. CONCLUSIONS: The use of a purely bicarbonate-buffered low-glucose degradation product solution significantly changes most of the peritoneal effluent markers measured, suggesting an improvement in peritoneal membrane integrity. Additionally, it seems to have a positive effect on residual renal function.

Comparison of plasma levels of cytokines and in vitro generation of reactive oxygen species after nicotine infusion in nicotine users with normal and impaired renal function.

Several in vitro and animal studies suggest effects of nicotine on the immune system, but little evidence exists regarding the in vivo immunomodulation of nicotine in humans. The increased use of nicotine replacement therapy to aid smoking cessation claims further understanding of how nicotine affects blood leukocytes. This is of particular importance when nicotine therapy is used in diseases associated with alterations of the immune system, such as chronic renal failure. The present study evaluates the acute effects of nicotine infusion (NI) on some immunoregulatory functions in seven healthy subjects and seven patients with renal failure. All subjects were nicotine users and had refrained from using nicotine for 36 h before NI. Blood was collected before, immediately after, and 2 h after NI. Plasma concentrations of intercellular adhesion molecule-1 (ICAM-1) and the cytokines interleukin-2 (IL-2), IL-4, IL-10, interferon-gamma and RANTES were measured using specific immunoassays. The generation of reactive oxygen species (ROS) induced by formyl-methionyl-leucyl-phenylalanine (fMLP), Ristocetin, adenosine 5'-diphosphate, or collagen was registered in whole blood as luminol-dependent chemiluminescence. Except for fMLP, these compounds induce leukocyte ROS generation by platelet mediated mechanisms. NI did not significantly affect the levels of the cytokines and ICAM-1 in any group. The peak and the persistent ROS production, induced by collagen and Ristocetin, was lower at some time points in patients with renal failure as compared to healthy subjects. Also in patients with renal failure, both peak height and persistent ROS generation induced by Ristocetin were reduced immediately after NI. Thus, nicotine inhibits some of the platelet-mediated activation of leukocyte ROS generation, and may be associated with platelet defects in renal failure.