Glucose degradation products (GDP) retard remesothelialization independently of D-glucose concentration.
BACKGROUND
Glucose degradation products (GDP) present in heat-sterilized dialysis fluids are thought to contribute to cellular dysfunction and membrane damage during peritoneal dialysis. To examine the effects of specific GDP on the remesothelialization process, the impact of conventional and low GDP peritoneal dialysis solutions, D-glucose, and individual GDP in a scratch-wounding model was assessed.


METHODS
Scratch (0.5 to 0.6 mm)-wounded human peritoneal mesothelial cells (HPMC) were treated, at pH 7.4, with either (1) control medium (M199), (2) laboratory-prepared heat or filter-sterilized solutions, (3) 10% to 80% vol/vol solution of Gambrosol or Gambrosol-trio (1.5% and 4.0% glucose), (4) D-glucose (5 to 80 mmol/L), or (5) individual or combined GDP [acetaldehyde, formaldehyde, glyoxal, methylglyoxal, 3-deoxyglucosone (3-DG), 5-hydroxy methylfufural (5-HMF), or 3,4-di-deoxyglucosone-3-ene (3,4-DGE)]. Wound closure was recorded by time-lapse photomicroscopy.


RESULTS
In untreated HPMC, the rate of wound closure was linear and the process was complete by 18.4 +/- 3.6 hours (N = 16). In wounded HPMC exposed to dilutions of heat-sterilized but not filtered laboratory solutions (1.5% or 4.0% glucose, pH 7.4), remesothelialization was significantly retarded (P = 0.04 and P = 0.009 vs. M199, respectively). In Gambrosol, remesothelialization was significantly retarded in both 1.5% and 4.0% solutions. In contrast in Gambrosol-trio-treated HPMC, this rate was not significantly reduced in either 1.5% or 4.0% glucose peritoneal dialysis fluids. Remesothelialization was dose-dependently retarded in HPMC exposed to 3,4-DGE (>10 microl/L), formaldehyde (>5 micromol/L) but not by exposure to the other GDP tested even at 5 times the concentration present in low glucose solutions. The rate of remesothelialization was not significantly altered by exposure to D-glucose concentrations up to 80 mmol/L.


CONCLUSIONS
These data identify that the formaldehyde and 3,4-DGE present in heat-sterilized peritoneal dialysis solutions are important in reducing mesothelial cell regeneration. Specifically targeting their removal may have major benefits in preserving the mesothelium during long-term peritoneal dialysis.
Morgan
Llinos W
LW
Institute of Nephrology, University of Wales College of Medicine, Cardiff, United Kingdom.
Wieslander
Anders
A
Davies
Malcolm
M
Horiuchi
Takashi
T
Ohta
Yuji
Y
Beavis
M Janine
MJ
Craig
Kathryn J
KJ
Williams
John D
JD
Topley
Nicholas
N
D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology* / Q000378:metabolism; D013242:Sterilization
D015314:Dialysis Solutions; D005947:Glucose