Effects of Neutral pH and Reduced Glucose Degradation Products in a New Peritoneal Dialysis Solution on Morphology of Peritoneal Membrane in Rats

2005 ◽  
Vol 100 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Osamu Ikehara ◽  
Hideki Nishimura ◽  
Takashi Naito ◽  
Chieko Higuchi ◽  
Tsutomu Sanaka
2004 ◽  
Vol 37 (12) ◽  
pp. 2069-2077 ◽  
Author(s):  
Tadashi Yamamoto ◽  
Tsuyoshi Izumotani ◽  
Senji Qkuno ◽  
Tomoyuki Yamakawa

2004 ◽  
Vol 24 (2) ◽  
pp. 115-122 ◽  
Author(s):  
Sun-Hee Park ◽  
Eun-Gyui Lee ◽  
In-San Kim ◽  
Yong-Jin Kim ◽  
Dong-Kyu Cho ◽  
...  

Background Long-term use of the peritoneal membrane as a dialyzing membrane is hampered by its eventual deterioration. One of the contributing factors is glucose degradation products (GDPs) in the dialysis solution. In this study, we evaluated the effect of a low GDP solution on peritoneal permeability, the structural stability of the peritoneal membrane, and vascular endothelial growth factor (VEGF) production in a chronic inflammatory infusion model of peritoneal dialysis (PD) in the rat. Methods Male Sprague–Dawley rats were divided into 3 groups: a conventional solution group (group C, n = 12), a test solution group (group T, n = 12), and a normal control group (group NC, n = 8). Group T rats were infused with low GDP solution (2.3% glucose solution with two compartments), and group C rats with conventional dialysis solution (2.3% glucose solution), adjusted to pH 7.0 before each exchange. Animals were infused through a permanent catheter with 25 mL of dialysis solution. In both groups, peritoneal inflammation was induced by infusing dialysis solution supplemented with lipopolysaccharide on days 8, 9, and 10 after starting dialysate infusion. Peritoneal membrane function was assessed before and 6 weeks after initiating dialysis using the 1-hour peritoneal equilibration test (PET) employing 4.25% glucose solution. Both VEGF and transforming growth factor β1 (TGFβ1) in the dialysate effluent were measured by ELISA. The number of vessels in the omentum was counted after staining with anti-von Willebrand factor, and the thickness of submesothelial matrix of the trichrome-stained parietal peritoneum was measured. Peritoneal tissue was analyzed for VEGF protein using immunohistochemistry. Results At the end of 6 weeks, the rate of glucose transport (D/D0, where D is glucose concentration in the dialysate and D0 is glucose concentration in the dialysis solution before it is infused into the peritoneal cavity) was higher in group T ( p < 0.05) than in group C. Dialysate-to-plasma ratio (D/P) of protein was lower in group T ( p < 0.05) than in group C; D/Purea, D/Psodium, and drain volumes did not differ significantly between groups C and T. Dialysate VEGF and TGFβ levels were lower in group T ( p < 0.05) than in group C. Immunohistochemical studies also revealed less VEGF in the peritoneal membranes of group T. There were significantly more peritoneal blood vessels in group C ( p < 0.05) than in group T, but the thickness of submesothelial matrix of the parietal peritoneum was not different between the two groups. The VEGF levels in the dialysate effluent correlated positively with the number of blood vessels per field ( r = 0.622, p < 0.005). Conclusion Using a chronic inflammatory infusion model of PD in the rat, we show that dialysis with GDP-containing PD fluid is associated with increased VEGF production and peritoneal vascularization. Use of low GDP solutions may therefore be beneficial in maintaining the function and structure of the peritoneal membrane during long-term PD.


2004 ◽  
Vol 24 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Katarzyna Wieczorowska–Tobis ◽  
Renata Brelinska ◽  
Janusz Witowski ◽  
Jutta Passlick–Deetjen ◽  
Thomas P. Schaub ◽  
...  

Background Acidic pH and the presence of glucose degradation products (GDP) are believed to compromise the biocompatibility of peritoneal dialysis fluids (PDF). The present study examines the effects of long-term exposure to GDP and low pH by comparing conventional PDF and a new, neutral pH, low GDP solution. Methods All experiments were performed using a chronic infusion model of dialysis in nonuremic rats. The animals were treated for 6 weeks with 2 daily injections of 4.25% glucose-containing PDF. The following PDF were tested: CAPD3 (single-chamber bag, low pH, high GDP), CAPD3 pH 7.4 (single-chamber bag, neutral pH, high GDP), CAPD3-Balance (double-chamber bag, neutral pH, low GDP). All test solutions were obtained from Fresenius Medical Care, Bad Homburg, Germany. Results After 6 weeks of exposure, peritoneal permeability to water, urea, creatinine, glucose, and sodium, assessed by peritoneal equilibration test, was similar in all groups. However, compared to other PDF, dialysis with CAPD3-Balance was associated with reduced concentrations of protein and hyaluronan in the dialysate, decreased peritoneal eosinophilia, and reduced dialysate levels of chemokines CCL2/MCP-1 and CCL5/RANTES. Morphologic changes in the peritoneal membrane of CAPD3-Balance-treated animals were much less pronounced and included reduced vascular density, preservation of the mesothelial monolayer and intercellular junction, and no reduplication of the submesothelial basement membrane. Conclusions A new generation of PDF with physiologic pH and low GDP level produce less irritation to the peritoneal membrane and better preserve its structural integrity. This effect seems to be related predominantly to minimized GDP concentrations.


2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 23-27 ◽  
Author(s):  
Anders Wieslander ◽  
Torbjörn Linden ◽  
Barbara Musi ◽  
Ola Carlsson ◽  
Reinhold Deppisch

Carbohydrates are not stable when exposed to energy; they degrade into new molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs during the heat sterilization procedure. The biological consequences of this degradation are side effects such as impaired proliferation and impaired host defense mechanisms, demonstrated in vitro for a great variety of cells. Several highly toxic compounds—such as formaldehyde and 3-deoxyglucosone—have been identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also well-known promoters of irreversible advanced glycation end-products (AGEs), which might participate in the long-term remodeling of the peritoneal membrane. Various approaches can be used to reduce the formation of glucose degradation products (GDPs) during heat sterilization. Some examples are shortening the sterilization time, lowering the pH, removing catalyzing substances, and increasing glucose concentration. The latter three factors are employed in the multi-compartment bag with a separate chamber containing pure glucose at high concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows reduced cytotoxicity, normalized host defense reactions, less AGE formation, and reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the clinical situation, the fluid turns out to be more biocompatible for the patient, causing less mesothelial cell damage, which in the long term could lead to a more intact peritoneal membrane. Conclusion Glucose degradation products in heat-sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation, and cause negative side effects for the patient. Using improved and well-controlled manufacturing processes, it is possible to produce sterile PD fluids with glucose as the osmotic agent but without the negative side effects related to GDPs.


2016 ◽  
Vol 36 (5) ◽  
pp. 569-572 ◽  
Author(s):  
Tatiana De los Ríos ◽  
Juan Pérez-Martínez ◽  
Jose Portoles ◽  
Monika Lichodziejewska-Niemierko ◽  
Maite Rivera ◽  
...  

Interference of conventional peritoneal dialysis fluids (cPDFs) with peritoneal membrane cell functions may be attributed to the dialysis fluid's low pH, high glucose concentration, and/or the presence of glucose degradation products (GDPs), the last of which leads to higher levels of advanced glycation end-products (AGEs). It has been suggested that the peritoneal membrane might be better preserved by using biocompatible solutions, including cancer antigetn 125 (CA125). This prospective, open-label, multicentre, randomized, controlled, cross-over phase IV study compared the in vivo biocompatibility of a neutral-pH, low-GDP peritoneal dialysis (PD) solution ( balance) with a cPDF in automated PD (APD) patients. Our study revealed a significantly increased appearance rate and concentration of CA125 in the peritoneal effluent of APD patients treated with the neutral-pH, low-GDP solution balance versus a conventional PD solution.


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