Strategies to Reduce Glucose Exposure in Peritoneal Dialysis Patients

2000 ◽  
Vol 20 (2_suppl) ◽  
pp. 37-41 ◽  
Author(s):  
Clifford J. Holmes ◽  
Ty R. Shockley
Keyword(s):  
Amino Acids ◽  
Peritoneal Dialysis ◽  
High Glucose ◽  
Degradation Products ◽  
Dialysis Patients ◽  
Carbohydrate Absorption ◽  
Glucose Degradation Products ◽  
Osmotic Agent ◽  
Glucose Exposure

Glucose has been used successfully for more than two decades in peritoneal dialysis, and in this regard, must be considered a safe and effective osmotic agent. Recently, however, insight has been growing about the potential for metabolic and peritoneal effects arising from long-term exposure to high glucose concentrations—for example, hyperlipidemia and loss of peritoneal ultrafiltration. Clinical concerns over exposure to excessive glucose and glucose degradation products (GDPs) during peritoneal dialysis can be significantly ameliorated by the use of non-glucose-based peritoneal dialysis (PD) solutions, in combination with more biocompatible glucose-based formulations. Peritoneal exposure to GDPs can be reduced by using low-GDP-containing glucose formulations and non glucose solutions such as amino acids and icodextrin. Peritoneal glucose exposure, hyperosmolar stress, and carbohydrate absorption can be reduced by using a combination of icodextrin and amino acids.

Biological Significance of Reducing Glucose Degradation Products in Peritoneal Dialysis Fluids

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 23-27 ◽  
Author(s):  
Anders Wieslander ◽  
Torbjörn Linden ◽  
Barbara Musi ◽  
Ola Carlsson ◽  
Reinhold Deppisch
Keyword(s):  
Peritoneal Dialysis ◽  
Side Effects ◽  
Host Defense ◽  
Degradation Products ◽  
Biological Significance ◽  
Peritoneal Membrane ◽  
Negative Side ◽  
Glucose Degradation Products ◽  
Negative Side Effects

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.

scholarly journals Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells

2001 ◽  
Vol 12 (11) ◽  
pp. 2434-2441 ◽  
Author(s):  
JANUSZ WITOWSKI ◽  
JUSTYNA WISNIEWSKA ◽  
KATARZYNA KORYBALSKA ◽  
THORSTEN O. BENDER ◽  
ANDRZEJ BREBOROWICZ ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
Human Peritoneal Mesothelial Cells ◽  
And Function ◽  
The Impact

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.

Osmotic Agents for Peritoneal Dialysis

1986 ◽  
Vol 9 (6) ◽  
pp. 387-390 ◽  
Author(s):  
R. Khanna ◽  
Z. J. Twardowski ◽  
D.G. Oreopoulos
Keyword(s):  
Amino Acids ◽  
Peritoneal Dialysis ◽  
Sole Agent ◽  
Dialysis Solution ◽  
Osmotic Agent ◽  
Peritoneal Dialysis Solution ◽  
Osmotic Agents ◽  
Near Future ◽  
Dialysis Solutions

Glucose has more advantages than drawbacks and is now the sole agent used in clinical practice. Yet there is interest in finding a substitute for glucose as an osmotic agent in peritoneal dialysis solution. Work has identified several promising agents such as albumin, amino acids, gelatin and glycerol but it appears that every one of them, including glucose, would be useful for a short-dwell or for a long-dwell exchange but not for both. Some of them, such as albumin and the amino acids, are close to being an ideal osmotic agent but are prohibitively costly to manufacture. We predict that interest in the future will focus on dialysis solutions containing a mixture of osmotic agents. Such a solution would be acceptable for both short and long-dwell exchanges. It will have a sufficiently low concentration of different agents to minimize toxicity and long-term undesirable side effects. We expect that solutions will be available to better meet patients needs in the near future.

scholarly journals The Effect of Far-Infrared Therapy on the Peritoneal Membrane Transport Characteristics of Uremic Patients Undergoing Peritoneal Dialysis: An Open-Prospective Proof-of-Concept Study

Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 669
Author(s):  
Ching-Po Li ◽  
Chyong-Mei Chen ◽  
Chia-Hao Chan ◽  
Szu-Yuan Li ◽  
Ming-Tsun Tsai ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Membrane Transport ◽  
Degradation Products ◽  
Far Infrared ◽  
Proof Of Concept ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Glucose Degradation Products ◽  
Average Status

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.

scholarly journals The impact of neutral-pH peritoneal dialysates with reduced glucose degradation products on clinical outcomes in peritoneal dialysis patients

2013 ◽  
Vol 84 (5) ◽  
pp. 969-979 ◽  
Author(s):  
Yeoungjee Cho ◽  
David W. Johnson ◽  
Sunil V. Badve ◽  
Jonathan C. Craig ◽  
Giovanni F.M. Strippoli ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Outcomes ◽  
Degradation Products ◽  
Dialysis Patients ◽  
Neutral Ph ◽  
Glucose Degradation Products ◽  
The Impact

scholarly journals Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products

2001 ◽  
Vol 59 (1) ◽  
pp. 348-357 ◽  
Author(s):  
Bengt Rippe ◽  
Ole Simonsen ◽  
Olle Heimbürger ◽  
Anders Christensson ◽  
Börje Haraldsson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Clinical Effects ◽  
Dialysis Fluid ◽  
Glucose Degradation Products ◽  
Peritoneal Dialysis Fluid

How to Avoid Glucose Degradation Products in Peritoneal Dialysis Fluids

2006 ◽  
Vol 26 (4) ◽  
pp. 490-497 ◽  
Author(s):  
Martin Erixon ◽  
Anders Wieslander ◽  
Torbjörn Lindén ◽  
Ola Carlsson ◽  
Gunita Forsbäck ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Glucose ◽  
Glucose Concentration ◽  
Degradation Products ◽  
Minor Effect ◽  
High Glucose Concentration ◽  
Temperature Dependent ◽  
Glucose Degradation Products ◽  
A Minor ◽  
Dialysis Fluids

Objective The formation of glucose degradation products (GDPs) during sterilization of peritoneal dialysis fluids (PDFs) is one of the most important aspects of biocompatibility of glucose-containing PDFs. Producers of PDFs are thus trying to minimize the level of GDPs in their products. 3,4-Dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP in PDFs. It exists in a temperature-dependent equilibrium with a pool of 3-deoxyglucosone (3-DG) and is a precursor in the irreversible formation of 5-hydroxymethyl furaldehyde (5-HMF). The aim of the present study was to investigate how to minimize GDPs in PDFs and how different manufacturers have succeeded in doing so. Design Glucose solutions at different pHs and concentrations were heat sterilized and 3-DG, 3,4-DGE, 5-HMF, formaldehyde, and acetaldehyde were analyzed. Conventional as well as biocompatible fluids from different manufacturers were analyzed in parallel for GDP concentrations. Results The concentrations of 3-DG and 3,4-DGE produced during heat sterilization decreased when pH was reduced to about 2. Concentration of 5-HMF decreased when pH was reduced to 2.6. After further decrease to a pH of 2.0, concentration of 5-HMF increased slightly, and below a pH of 2.0 it increased considerably, together with formaldehyde; 3-DG continued to drop and 3,4-DGE remained constant. Inhibition of cell growth was paralleled by 3,4-DGE concentration at pH 2.0 – 6.0. A high glucose concentration lowered concentrations of 3,4-DGE and 3-DG at pH 5.5 and of 5-HMF at pH 1. At pH 2.2 and 3.2, glucose concentration had a minor effect on the formation of GDPs. All conventional PDFs contained high levels of 3,4-DGE and 3-DG. Concentrations were considerably lower in the biocompatible fluids. However, the concentration of 5-HMF was slightly higher in all the biocompatible fluids. Conclusion The best way to avoid reactive GDPs is to have a pH between 2.0 and 2.6 during sterilization. If pHs outside this range are used, it becomes more important to have high glucose concentration during the sterilization process. There are large variations in GDPs, both within and between biocompatible and conventionally manufactured PDFs.

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 ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Blood Vessels ◽  
Glucose Concentration ◽  
Glucose Solution ◽  
Degradation Products ◽  
Peritoneal Membrane ◽  
Glucose Degradation Products ◽  
Dialysis Solution

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.

Can keto/amino acids reduce oxidative stress in peritoneal dialysis patients with hypoalbuminemia?

2021 ◽  
Author(s):  
Erdem Çankaya ◽  
Yusuf Bilen ◽  
Abdullah Uyanık ◽  
Hasan Dogan ◽  
Ahmet Kızıltunç ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Peritoneal Dialysis ◽  
Dialysis Patients
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