Search

Background: Long-term peritoneal dialysis (PD) with conventional glucose based, lactate-buffered PD fluids may lead to morphological and functional alterations of the peritoneal membrane. It was hypothesized that long-term exposure to a different buffer and a mixture of osmotic agents would cause less peritoneal abnormality., Objectives: To investigate the effects of long-term exposure to a bicarbonate/lactate-buffered dialysis solution with a mixture of osmotic agents: glycerol 1.4%, amino acids 0.5%, and dextrose 1.1% (= 1% glucose) (GLAD) in a rat model with chronic kidney failure., Methods: All rats underwent a peritoneal catheter implantation and a 70% nephrectomy. Thereafter, the rats were randomly divided into 3 groups: GLAD, 3.86% Dianeal (Baxter, Nivelles, Belgium), and buffer (Physioneal without glucose, Baxter). All rats were infused daily for 16 weeks with the appropriate PD fluid. Afterwards, a peritoneal permeability analysis (SPARa) was performed using 3.86% Physioneal in all groups. After the SPARa, the rats were sacrificed to obtain tissue samples for morphometric determinations. Omental tissue was stained with picro Sirius red for assessment of fibrosis and with CD31 for vessel density., Results: GLAD and Dianeal showed faster small solute transport compared to the hypotonic buffer. No differences between the groups were present in ultrafiltration. Dianeal had the lowest value for free water transport and the highest protein clearances. Total triglyceride in plasma was not different between GLAD and the buffer. Vessel density after GLAD exposure (20 V/F) was very similar to the value found for the buffer solution (17 V/F); Dianeal caused a significantly higher value (35 V/F, p < 0.01). Also, the amount of fibrosis was higher in the Dianeal-exposed rats (p < 0.01)., Conclusion: Both hypertonic dialysis solutions increased peritoneal solute transport. GLAD exposure was associated with the best preservation of peritoneal morphology. The results of GLAD were very similar to those of the bicarbonate/lactate-buffered solution without osmotic agents. Studies in humans are needed for further assessment of GLAD.

Chronic exposure to peritoneal dialysis (PD) solutions is associated with a low-grade local inflammatory state of the peritoneum. The occurrence of culture-negative peritonitis in some PD patients treated with icodextrin focused our interest on subclinical inflammation in icodextrin-treated patients without peritonitis. The aim of the present study was to compare signs of inflammation in icodextrin-treated patients with the same signs in patients using glucose/lactate-based (GL) dialysis solutions only. Overnight PD effluents from 19 patients treated with icodextrin and 19 patients treated with GL were investigated for leukocyte count (LC) and differentiation (LD), and for dialysate concentrations of cancer antigen 125 (CA125, the marker of mesothelial cell mass) and hyaluronan (marker of inflammation and tissue remodeling in the peritoneal cavity). Blood cell counts and serum dextran antibodies (DA) were also determined. Total LC in the GL group was significantly lower than that in the icodextrin group. The LD was not different between the two groups, except for the percentage of eosinophils. The blood cell count did not differ between the groups. The median value of DA was similar in both groups. The hyaluronan concentration was markedly higher in the icodextrin group. No significant difference was found for dialysate CA125. In conclusion, the higher effluent cell count, higher percentage of eosinophils, and higher effluent hyaluronan levels in icodextrin-treated patients are consistent with a greater degree of subclinical inflammation during icodextrin treatment than during GL treatment.

Objective: Peritoneal dialysis (PD) with a 7.5% icodextrin-containing dialysis solution provides prolonged ultrafiltration compared with glucose-based dialysis solutions. Colloid osmosis is the most likely mechanism, but studies in rats suggest it is caused by an increase in osmolality due to degradation of icodextrin. Therefore, human spent dialysate was analyzed with high-performance liquid chromatography (HPLC) using gel permeation size-exclusion chromatography. An increasing peak (with a low molecular weight, < 1000 Da) was observed during the dwell. The aim of this study was to quantitate breakdown products of icodextrin (which could explain this peak) and investigate whether there was a relationship with dialysate amylase concentration and dialysate osmolality., Design: Long-dwell effluents (dwell time 9.15- 14.30 hours) obtained from 12 PD patients using a 7.5% icodextrin solution during the night were analyzed. The following icodextrin breakdown products were measured: maltotetraose (G4), maltotriose (G3), maltose (G2), and glucose (G1). In 6 of these patients, the sugars maltoheptaose (G7), maltohexaose (G6), and maltopentaose (G5) were also determined in both effluent and plasma. In addition, G4, G3, G2, and G1 were measured in four Wistar rats during a 6-hour dwell study., Results: In the human studies, the median distribution of the sugars in the effluent was G4,6.7%; G3,16.5%; G2, 23.1%; and G1, 53.5%. The osmolality in spent dialysate ranged between 288 and 326 mOsm/kg H2O. The median contribution of the sugars G2 - G4 was 5.4 mOsm/kg H2O. No correlation was present between dialysate osmolality and duration of the dwell (r= -0.04, p= 0.91); nor was there a relation between the concentration of G2 and duration of the dwell (r = 0.50, p = 0.10). No relationship was found between the amount of amylase and the concentration of G2 in the effluent (r = 0.49, p = 0.10), nor between the total concentration of the sugars G2 - G4 in the spent dialysate and dialysate osmolality (r = -0.31, p = 0.33). However, a strong correlation was seen between urea concentration and osmolality (r= 0.85, p < 0.001), and also between sodium concentration and dialysate osmolality in the spent dialysate (r = 0.92, p < 0.0001). The levels of the sugars G2, G3, and G4 in effluent were higher than in unused dialysate, but lower than or similar to plasma levels. Concentrations of the sugars G5, G6, and G7 were lower in spent dialysate than in unused dialysate, and higher than in plasma. In the rat study, dialysate osmolality increased with the duration of the dwell. A clear relationship was present between osmolality and concentration of the sugars G2 - G4 in the effluent. The median amount of amylase in the effluent was 1252 U/L., Conclusion: A 7.5% icodextrin-based dialysis solution used during the long exchange caused only a slight increase in dialysate osmolality in humans. The osmolality at the end of the dwell in the human situation was dependent mainly on concentrations of the small solutes urea and sodium in the effluent. The contribution of icodextrin degradation products was marginal. In the rat, however, a clear relationship was present between osmolality and icodextrin degradation products in spent dialysate, explaining the increased dialysate osmolality at the end of the dwell. The difference between the two species can be explained by the very high amylase concentrations in the rat, leading to a rapid degradation of icodextrin. The rat is therefore not suitable to study peritoneal fluid kinetics using icodextrin as an osmotic agent.

Objective: This study reviews relevant publications on the peritoneal vasculature and tries to establish morphological-functional relationships., Design: The design is a review article., Results: Recent morphological studies in peritoneal dialysis (PD) patients have shown the presence of diabetiform neoangiogenesis in long-term peritoneal dialysis. The same abnormalities could be induced in rats administered a high glucose dialysis solution daily for 20 weeks. The animals showed functional abnormalities in peritoneal transport similar to those found in long-term PD patients. Evidence was obtained in patients that vascular endothelial growth factor could be involved in glucose-induced peritoneal neoangiogenesis., Conclusions: Diabetiform peritoneal neoangiogenesis is an important pathogenetic factor in ultrafiltration failure in long-term peritoneal dialysis patients.