title: 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 micromol/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.
authors.affiliation: Corporate Research, Gambro AB, University of Lund, Lund, Sweden. martin.erixon@gambro.com
authors.forename: Martin
authors.initials: M
authors.lastname: Erixon
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lindén
authors.forename: Per
authors.initials: P
authors.lastname: Kjellstrand
authors.forename: Ola
authors.initials: O
authors.lastname: Carlsson
authors.forename: Malin
authors.initials: M
authors.lastname: Ernebrant
authors.forename: Gunita
authors.initials: G
authors.lastname: Forsbäck
authors.forename: Anders
authors.initials: A
authors.lastname: Wieslander
authors.forename: Jan Ake
authors.initials: JA
authors.lastname: Jönsson
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D015314:Dialysis Solutions / Q000378:metabolism*; D004356:Drug Storage; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism; D013242:Sterilization
chemical_list: D000447:Aldehydes; D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; C008046:5-hydroxymethylfurfural; D003847:Deoxyglucose; D005662:Furaldehyde; C016350:3-deoxyglucosone