A PYRUVATE-BUFFERED DIALYSIS FLUID INDUCES LESS PERITONEAL ANGIOGENESIS AND FIBROSIS THAN A CONVENTIONAL SOLUTION (original) (raw)
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Peritoneal Dialysis International, 2010
Background: Single-dwell studies in rats and humans have shown that supplementing citrate for lactate in peritoneal dialysis (PD) fluids improves ultrafiltration (UF). ♦ ♦ ♦ ♦ ♦ Methods: The long-term effects of citrate-substituted PD fluids on PD catheter patency, UF, and peritoneal morphology were evaluated in a rat model over 5 weeks of daily PD fluid exposure. A standard 2.5% glucose 40 mmol/L lactate PD fluid and a corresponding 10/30 mmol/L citrate/lactate PD fluid were compared. In a control group, rats with catheters received no PD fluid. ♦ ♦ ♦ ♦ ♦ Results: The average patency time (% of 36 days) of silicone rubber PD catheters was significantly longer in the citrate PD group (98.8% ± 1.2%) and the control group (100% ± 0%) compared to the lactate PD group (54.7% ± 9.5%). In a separate experiment, heparin-coated polyurethane catheters were used to study peritoneal morphology and fluid transport. The citrate group had a higher net UF than the lactate group at the beginning and at the end of the 5 weeks. During the experiment, both fluid-treated groups suffered from UF loss; the control group showed the highest net UF at the end of the 5 weeks. Peritoneal vascular density and submesothelial thickness, indicators of angiogenesis and fibrosis, were not significantly different among the groups. Fibrosis was significantly negatively correlated to osmotic UF. ♦ ♦ ♦ ♦ ♦ Conclusion: A positive acute effect of citrate on UF was confirmed and conserved over time. Citrate PD strongly improved PD catheter patency time compared with lactate. Both citrate PD and lactate PD induced negative long-term effects on UF compared with control animals.
Nephrology Dialysis Transplantation, 2005
Background. Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. However, the (ir)reversibility of these pathological changes of the peritoneum is not understood fully. Methods. In an experimental PD model, rats (n ¼ 15) received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters connected to implanted subcutaneous mini vascular access ports. After 5 weeks of treatment, the first group of animals (PDF; n ¼ 10) was sacrificed, while peritoneal catheters of the remaining group of rats (PD-rest; n ¼ 5) were removed 1 week later. The latter group (PD-rest) was sacrificed 12 weeks after removing catheters. At both time points, untreated rats were included as controls. Cellular and morphological parameters were analysed by light and electron microscopy. Results. Rats exposed to PD fluid for 5 weeks showed a severe angiogenesis in various peritoneal tissues. Peritoneal rest resulted in a significant reduction in blood vessel density in visceral (mesentery, P<0.05), but not in parietal peritoneum. Five weeks' exposure to PD fluid resulted in a profound fibrosis in the parietal peritoneum, whereas the degree of fibrosis was significantly reduced in the PD-rest group (P<0.02). Daily exposure to PD fluid induced a higher number of mast cells in the omentum compared with untreated rats, whereas peritoneal rest normalized the increased mast cell density completely (P<0.03). Likewise, continued PD fluid instillation evoked a strong omental milky spot response, which was returned to the control level after peritoneal rest (P<0.009). Furthermore, the number of mesothelial cells on the liver was significantly increased in rats treated with PD fluid, whereas animals from the PD-rest group had a lower number of mesothelial cells, although this was not statistically significant (P ¼ 0.08). Finally, as evidenced by electron microscopy, daily exposure to PD fluid resulted in severe damage to the mesothelial cell layer covering the peritoneum, whereas this cell layer was completely recovered after peritoneal rest. Conclusions. We show that PD fluid-induced cellular and morphological alterations of the peritoneal membrane are generally reversible.
Better Preservation of the Peritoneum in Rats Exposed to Amino Acid-Based Peritoneal Dialysis Fluid
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 2005
BackgroundGlucose-containing peritoneal dialysis fluids (PDF) show impaired biocompatibility, which is related partly to their high glucose content, presence of glucose degradation products, low pH, and lactate buffer, or a combination of these factors. In a rat chronic peritoneal exposure model, we compared effects of an amino acid-based PDF (AA-PDF) with a glucose-containing PDF on the peritoneal microcirculation and morphology.MethodTwo groups of rats received 10 mL of either fluid daily for 5 weeks via peritoneal catheters connected to implanted subcutaneous mini vascular access ports. Leukocyte–endothelium interactions in the mesenteric venules were investigated by intravital microscopy. Quantification of angiogenesis and fibrosis and inspection of the mesothelial cell layer were performed by light and electron microscopy.ResultsDaily exposure to glucose-containing PDF resulted in a significant increase in the number of rolling leukocytes in mesenteric venules, whereas instilla...
Development of a Peritoneal Sclerosis Rat Model Using a Continuous-Infusion Pump
Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 2008
Objective Encapsulating peritoneal sclerosis (EPS) is a serious complication of continuous ambulatory peritoneal dialysis. Previous studies have created peritoneal sclerosis rat models using daily intraperitoneal injection of chlorhexidine gluconate (CG), but this technique is cumbersome and thickening of the peritoneum makes it difficult to evaluate the injection site. We therefore aimed to make a rat model using a continuous-infusion pump. Methods Various concentrations of CG (5%, 8%, 10%, 12%, and 14%) in ethanol were dissolved in saline within the infusion pumps, each of which was placed in the lower abdominal cavity of a male Wister rat. After a peritoneal equilibration test was performed, the rats were sacrificed and the lower anterior parietal and visceral peritoneum was removed. Each excised peritoneum was analyzed by macroscopic and microscopic examinations, including immunohistochemistry for the expression of transforming growth factor-beta 1 (TGF-β1), vascular endothelial...
Nephrology Dialysis Transplantation, 2007
Introduction and Aims: Ultrafiltration failure is one of the major problems associated with peritoneal dialysis (PD) and has been associated with increased membrane permeability and fibrosis. Recent studies have focused on increased endothelin-1 (ET-1) release from peritoneal mesothelial cells during PD leading to increased collagen synthesis and fibrosis of the peritoneum. The aim of this study was to investigate the effect of ET-1 on peritoneal permeability. Hence, Ussing chamber experiments assessing the transmesothelial electrical resistance (R TM ]) of isolated visceral sheep peritoneum were performed. Methods: Peritoneal samples were obtained from twelve adult sheep. The samples were collected from the slaughter house and transferred to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4°C, pH 7.5), oxygenated with 95%O 2 /5%CO 2. Within 30 minutes of the death of the animal a visceral peritoneal planar sheet was mounted in an Ussing-type chamber and ET-1 (10-7 M) was added both apically and basolaterally. R TM was measured before and serially after addition of ET-1 for 30min. Measurements were held at 37°C, since active ion transport is temperature dependent. The results presented are the means (±SE) of twelve experiments. Results: The control R TM was 22.8±0.56 •cm 2. Addition of ET-1 to the basolateral side induced within 1 min an increase of R TM to 35.48±0.49 •cm 2 (p=0.012), which persisted in such value levels throughout the experiment. ET-1 action on the apical side was similar with a rapid rise of R TM to 39.08±0.69 •cm 2 (p=0.007) and a subsequent value persistence. Conclusions: ET-1 was found to increase the R TM , therefore decrease the peritoneal permeability, rapidly when added both apically and basolaterally. The physiological basis of our finding could be attributed to transcellular Na + transport inhibition. This effect could be mediated through ET-1 sensitive mesothelial sodium channels, since ET-1 has been shown to act as an inhibitor of epithelial sodium channels (ENaC) in previous studies.
NDT Plus, 2008
Background. Long-term peritoneal dialysis (PD) may lead to functional and morphologic changes in the peritoneal membrane, probably because of the continuous exposure to conventional dialysis solutions. Methods. The morphologic changes include neoangiogenesis and fibrosis. The authors of this article developed a long-term peritoneal exposure model in rats, in which the morphological alterations could be induced after daily peritoneal infusion of a 3.86% glucose/lactate-buffered conventional PD solution. Results and Conclusions. In the present article, a review of the model and of the results obtained with various available and experimental solutions is given. It appeared that high lactate concentrations contributed to the glucose-induced neoangiogenesis by pseudohypoxia. Glucose degradation products were probably more important in the induction of peritoneal fibrosis. The promising results of a combination of amino acids, glycerol and glucose, each in a low concentration, buffered with either pyruvate or bicarbonate/lactate, are presented and discussed. The combination of glycerol, amino acids and dextrose, dissolved in a bicarbonate/lactate buffer (GLAD), may be an option for a new generation of dialysis fluids.
Rat models in peritoneal dialysis
Nephrology Dialysis Transplantation, 2001
Background. It is widely accepted that the currently used dialysis solutions are not biocompatible with the peritoneal membrane. Therefore, animal studies have been performed to study different aspects of peritoneal dialysis. However, representative models mimicking the human situation are not yet available. Methods. The effect of a single injection of peritoneal dialysis (PD)¯uid on the cellular composition was studied. Thereafter, the effect of a single injection of PD¯uid on bacterial clearing was tested over time. Finally, an in vivo rat model was established to study the effects of long-term exposure to PD¯uid on the peritoneal membrane and the local host defence (peritoneal cells). Results. In the rat model, long-term daily exposure is possible. The`drop-out' after 9±10 weeks on the most commonly used PD¯uid Dianeal 3.86%, however, is ;50% due to omental wrapping. In the remaining study group, large differences were observed (as compared with controls), especially with respect to morphological parameters. Conclusions. The rat peritoneal continuous exposure model seems to have potential for intervention studies, since it uses no additions, no antibiotics and no omentomectomy, and gives continuous long-term exposure to PD¯uid. However, problems still remain: drop-out' is quite often seen and this non-uraemic exposure model does not totally mimic the situation present in continuous ambulatory PD patients.
Biocompatibility of peritoneal dialysis fluids: long-term exposure of nonuremic rats
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 microm), vascular density, vascular endothel...