Biological significance of reducing glucose degradation products in peritoneal dialysis fluids.
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.


CONCLUSIONS
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.
Wieslander
A
A
Gambro Corporate Research, Lund, Sweden. anders.wieslander@gambro.com
Linden
T
T
Musi
B
B
Carlsson
O
O
Deppisch
R
R
D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000737:chemistry* / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010529:Peritoneal Cavity / Q000166:cytology; D010530:Peritoneal Dialysis; D013242:Sterilization
D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D005947:Glucose