PD Fluids Contain High Concentrations of Cytotoxic GDPs Directly after Sterilization

Abstract

Objective Glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids are cytotoxic and affect the survival of the peritoneal membrane. One of the most reactive GDPs in PD fluids is 3,4-dideoxyglucosone-3-ene (3,4-DGE). 3,4-DGE has been reported as an intermediate between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl furaldehyde (5-HMF) during degradation of glucose. In PD fluids, 3,4-DGE exists in a temperature-dependent equilibrium with a pool of unidentified substances. The aim of this study was to explore this equilibrium and its temperature dependence during the first months of storage after the sterilization procedure. Methods GDPs and inhibition of cell growth (ICG) were measured directly after sterilization of the PD fluid and during storage at different temperatures for 60 days. The following GDPs were analyzed: 3-DG, 3,4-DGE, 5-HMF, formaldehyde, acetaldehyde, glyoxal, and methylglyoxal. Results Immediately after sterilization, the concentration of 3,4-DGE was 125 μmol/L. During the first weeks of storage, it decreased by about 80%. At the same time, the 3-DG concentration increased. None of the other GDPs were significantly affected. Cytotoxicity correlated well with the concentration of 3,4-DGE. When pure 3,4-DGE was substituted for the lost amount of 3,4-DGE after 30 days of storage, the initial ICG was almost completely regained. Conclusions Heat sterilization of PD fluids promotes the formation of large quantities of 3,4-DGE, rendering the fluid highly cytotoxic. During storage, the main part of 3,4-DGE is reversibly converted in a temperature-dependent manner to a less cytotoxic pool, consisting mainly of 3-DG. Cytotoxicity seems to be dependent exclusively on 3,4-DGE. In order to avoid higher levels of 3,4-DGE concentrations, PD fluids should not be used too soon after sterilization and should not be stored at temperatures above room temperature.

Reducing the formation of glucose degradation products in peritoneal dialysis solutions by ultrahigh temperature ohmic heating

“…In addition, GO was not detected when sterilized in the conventional treatments. These results are in line with previously reported concentrations, by Erixon et al [2] and Okabe et al [34]. This observation indicates that the composition being used in this study as well as the analytical procedures is adequate.…”

“…It appears that using the ohmic heating at 1258C does not form at all or form minor concentrations of the GDPs tested. When these results are compared to a study conducted by Erixon et al [2] it was observed that immediately after sterilization at 1218C for 40 min (F 0 = 40), the concentration of 3-DG was l230 lM.…”

“…Glucose is easily metabolized and is the most important energy source for living cells. Before use, PD fluids are sterilized, normally by exposure of the fluids to high temperatures (approximately 1208C) for a significant time (20-40 min) [2]. The sterilization at these temperatures can generate reactive intermediates that induce glycation in the patients on PD.…”

“…However, the number of identified GDPs represents only a fraction of a large number of compounds that can be generated from glucose. 3,4-DGE was recently identified as the most biologically reactive GDP in PD fluids [2].…”

PD solutions: New and old

“…16,17,[24][25][26][27][28] Sterilization of glucose-containing PD solutions in buffer at a pH of 5.5, which is typical for conventional standard solutions, unfortunately is far from optimal and leads to a signifi cant amount of GDPs. 29,30 Data suggest that the acidic pH that is a feature of all conventional and some new solutions has toxic effects. Investigating the cytotoxicity of different components of standard PD solutions, Wieslander showed that a pH of 5.5 inhibited cell growth to 100%, while lactate at neutral pH had no signifi cant adverse effect.…”