Effect of Glucose Degradation Products on the Peritoneal Membrane in a Chronic Inflammatory Infusion Model of Peritoneal Dialysis in the Rat

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.

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.


Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 669
Author(s):  
Ching-Po Li ◽  
Chyong-Mei Chen ◽  
Chia-Hao Chan ◽  
Szu-Yuan Li ◽  
Ming-Tsun Tsai ◽  
...  

Long-term peritoneal dialysis (PD) can lead to detrimental changes in peritoneal membrane function, which may be related to the accumulation of glucose degradation products. A previous study demonstrated that 6 months of far-infrared (FIR) therapy may decrease glucose degradation products in PD dialysate. Due to limited literature on this matter, this study aims to investigate the effect of FIR therapy on the peritoneal membrane transport characteristics of PD patients. Patients were grouped according to baseline peritoneal transport status: lower transporters (low and low-average) and higher transporters (high-average and high). Both groups underwent 40 min of FIR therapy twice daily for 1 year. In lower transporters, FIR therapy increased weekly dialysate creatinine clearance (6.91 L/wk/1.73 m2; p = 0.04) and D/P creatinine (0.05; p = 0.01). In higher transporters, FIR therapy decreased D/P creatinine (−0.05; p = 0.01) and increased D/D0 glucose (0.05; p = 0.006). Fifty percent of high transporter patients shifted to high-average status after FIR therapy. FIR therapy may decrease D/P creatinine for patients in the higher transporter group and cause high transporters to shift to high-average status, which suggests the potential of FIR therapy in improving peritoneal membrane function in PD patients.


1989 ◽  
Vol 9 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Min Sun Park ◽  
Jean Lee ◽  
Moon Sung Lee ◽  
Seung Ho Baick ◽  
Seung Duk Hwang ◽  
...  

In order to evaluate peritoneal membrane function and responsiveness of peritoneal microcirculation to vasoactive agents in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, we studied peritoneal clearances of urea (Curea) and creatinine (Ccr), protein concentrations in drained dialysate (D PC), peritoneal glucose absorption (% GA), and drained dialysate volume ( VD) before and after nitroprusside (NP) addition to dialysis solution in 17 long-term CAPD patients (mean duration of CAPD: 52 months) and the results were compared to those of 18 patients who were just trained for CAPD (mean duration: 0.6 month). There were no differences in the control (without NP) Curea, Ccr, D PC, %GA, and VD between the new and long-term CAPD patients. Curea, Ccr, and D PC increased significantly with NP in both new and long-term patients. Curea and Ccr with NP were not different between the new and long-term patients but D PC with NP was significantly lower in the long-term CAPD patients. The results of this study suggest that peritoneal solute clearances and the responsiveness of peritoneal microcirculation to NP remain unchanged after four years of CAPD, despite recurrent episodes of peritonitis.


2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 107-113
Author(s):  
Talerngsak Kanjanabuch ◽  
Monchai Siribamrungwong ◽  
Rungrote Khunprakant ◽  
Sirigul Kanjanabuch ◽  
Piyathida Jeungsmarn ◽  
...  

⋄ Background Continuous exposure of the peritoneal membrane to dialysis solutions during long-term dialysis results in mesothelial cell loss, peritoneal membrane damage, and thereby, ultrafiltration (UF) failure, a major determinant of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, none of tests available today can predict long-term UF decline. Here, we propose a new tool to predict such a change. ⋄ Mesothelial cells from 8-hour overnight effluents (1.36% glucose dialysis solution) were harvested, co-stained with cytokeratin (a mesothelial marker) and TUNEL (an apoptotic marker), and were counted using flow cytometry in 48 patients recently started on CAPD. Adequacy of dialysis, UF, nutrition status, dialysate cancer antigen 125 (CA125), and a peritoneal equilibration test (3.86% glucose peritoneal dialysis solution) were simultaneously assessed and were reevaluated 1 year later. ⋄ Results The numbers of total and apoptotic mesothelial cells were 0.19 ± 0.19 million and 0.08 ± 0.12 million cells per bag, respectively. Both numbers correlated well with the levels of end dialysate–to–initial dialysate (D/D0) glucose, dialysate-to-plasma (D/P) creatinine, and sodium dipping. Notably, the counts of cells of both types in patients with diabetes or with high or high-average transport were significantly greater than the equivalent counts in nondiabetic patients or those with low or low-average transport. A cutoff of 0.06 million total mesothelial cells per bag had sensitivity of 1 and a specificity of 0.75 in predicting a further decline in D/D0 glucose and a sensitivity of 0.86 and a specificity of 0.63 to predict a further decline in UF over a 1-year period. In contrast, dialysate CA125 and other measured parameters had low predictive values. ⋄ Conclusions The greater the loss of exfoliated cells, the worse the expected decline in UF. The ability of a count of mesothelial cells to predict a future decline in UF warrants further investigation in clinical practice.


2004 ◽  
Vol 37 (12) ◽  
pp. 2069-2077 ◽  
Author(s):  
Tadashi Yamamoto ◽  
Tsuyoshi Izumotani ◽  
Senji Qkuno ◽  
Tomoyuki Yamakawa

2001 ◽  
Vol 12 (11) ◽  
pp. 2434-2441 ◽  
Author(s):  
JANUSZ WITOWSKI ◽  
JUSTYNA WISNIEWSKA ◽  
KATARZYNA KORYBALSKA ◽  
THORSTEN O. BENDER ◽  
ANDRZEJ BREBOROWICZ ◽  
...  

Abstract. Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.


2005 ◽  
Vol 25 (3_suppl) ◽  
pp. 135-136
Author(s):  
Cornelis H. Schröder

Since children on dialysis are treated most often with nightly intermittent peritoneal dialysis, adequacy of dialysis is determined by the number and duration of cycles, the volume of the dialysis fluid applied, and the choice of dialysis solution. The number and duration of cycles are dependent on the maximal acceptable duration of night rest and the permeability properties of the peritoneal membrane. The latter can be established by performance of a peritoneal equilibration test. The volume used should be about 1200 mL/m2 body surface area, and intraperitoneal pressure should be between 5 and 15 cm H2O. The dialysis solution administered should have a glucose concentration as low as possible, and an icodextrin daytime dwell may be considered.


Sign in / Sign up

Export Citation Format

Share Document