The Japan Balance Study: Evaluation of peritoneal dialysis fluid with neutral pH and low levels of glucose degradation products in peritoneal dialysis patients

Objective To review protein glycation and advanced glycation end-product formation with particular reference to its occurrence in the peritoneum following exposure to peritoneal dialysis fluid. Data sources Articles identified through searches on MEDLINE and BIDS and references cited therein. Study selection Studies on the interaction of amino groups with glucose, maltose and glucose polymers. Studies containing evidence of peritoneal advanced glycation end-product formation. Data extraction Studies evaluated as to whether they are in vivo, ex vivo or in vitro under non-physiological or physiological conditions. Results Protein glycation is slower with maltose and glucose polymers than with equimolar glucose. Advanced glycation end-product formation occurs with all three sugars, but to a greater extent after standard heat sterilization of dialysis fluid and to a lesser extent in heat sterilized fluids containing icodextrin rather than glucose. Glucose degradation products significantly contribute to protein-linked advanced glycation end-productlike fluorescence. Histology and immunohistochemistry demonstrate diabetiform changes and advanced glycation end-products in the peritoneal membrane following exposure to glucose-containing peritoneal dialysis fluids. Their presence is likely to be detrimental to peritoneal function and may contribute to loss of ultrafiltration. Conclusions Advanced glycation end-product formation is lower but still significant with heat sterilized peritoneal dialysis fluid containing icodextrin than with glucose. More research is needed to investigate the interaction of glucose degradation products and glucose polymers with proteins and the possible consequences of advanced glycation end-product formation on peritoneal function.

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A New Neutral-Ph Low-Gdp Peritoneal Dialysis Fluid

Peritoneal Dialysis International ◽

10.3747/pdi.2011.00072 ◽

2012 ◽

Vol 32 (4) ◽

pp. 444-452 ◽

Cited By ~ 14

Author(s):

Rainer Himmele ◽

Lynn Jensen ◽

Dominik Fenn ◽

Chih-Hu Ho ◽

Dixie-Ann Sawin ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Medical Care ◽

Degradation Products ◽

The United States ◽

Neutral Ph ◽

Glucose Degradation Products ◽

Baxter Healthcare ◽

Peritoneal Dialysis Fluid ◽

The Us ◽

Age Range

BackgroundConventional peritoneal dialysis fluids (PDFs) consist of ready-to-use solutions with an acidic pH. Sterilization of these fluids is known to generate high levels of glucose degradation products (GDPs). Although several neutral-pH, low-GDP PD solutions have been developed, none are commercially available in the United States. We analyzed pH and GDPs in Delflex Neutral pH (Fresenius Medical Care North America, Waltham, MA, USA), the first neutral-pH PDF to be approved by the US Food and Drug Administration.MethodsWe evaluated whether patients (n = 26; age range: 18 - 78 years) could properly mix the Delflex Neutral pH PDF after standardized initial training. We further analyzed the concentrations of 10 different glucose degradation products in Delflex Neutral pH PDF and compared the results with similar analyses in other commercially available biocompatible PDFs.ResultsAll pH measurements (n = 288) in the delivered Delflex Neutral pH solution consistently fell within the labeled range of 7.0 ± 0.4. Analysis of mixing errors showed no significant impact on the pH results. Delflex Neutral pH, Balance (Fresenius Medical Care, Bad Homburg, Germany), BicaVera (Fresenius Medical Care), and Gambrosol Trio (Gambro Lundia AB, Lund, Sweden) exhibited similar low total GDP concentrations, with maximums in the 4.25% solutions of 88 μmol/L, 74 μmol/L, 74 μmol/L, and 79 μmol/L respectively; the concentration in Physioneal (Baxter Healthcare Corporation, Deerfield, IL, USA) was considerably higher at 263.26 μmol/L The total GDP concentration in Extraneal (Baxter Healthcare Corporation) was 63 μmol/L, being thus slightly lower than the concentrations in the 4.25% glucose solutions, but higher than the concentrations in the 1.5% and 2.5% glucose solutions.ConclusionsThe new Delflex Neutral pH PDF consistently delivers neutral pH with minimal GDPs.

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Peritoneal Dialysis Solutions Low in Glucose Degradation Products—evidence for Clinical Benefits

Peritoneal Dialysis International ◽

10.1177/089686080802803s23 ◽

2008 ◽

Vol 28 (3_suppl) ◽

pp. 123-127

Author(s):

Tadashi Tomo

Keyword(s):

Peritoneal Dialysis ◽

Vascular Function ◽

Degradation Products ◽

Peritoneal Mesothelial Cells ◽

Advanced Glycosylation End Products ◽

Glucose Degradation Products ◽

Peritoneal Dialysis Fluid ◽

Clinical Benefits ◽

Human Peritoneal Mesothelial Cells ◽

Peritoneal Function

In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has bio-compatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.

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