Chemical and physiological relevance of glucose degradation products in peritoneal dialysis.
Fibrosis and vascular sclerosis are main complications that limit the long-term application of peritoneal dialysis (PD). Low biocompatibility has been largely attributed to the presence of glucose degradation products (GDPs), which are formed during the heat sterilization of PD fluids. GDPs readily modify proteins in the peritoneum, leading to a decline of their biological function. After absorption, GDPs can also promote systemic protein glycation. Additionally, GDPs may augment DNA glycation, a process enhanced in uremia. Apart from their glycating activity, GDPs induce cytotoxicity and interfere with cell signaling in peritoneal mesothelial cells. Targeted screening revealed the nature of the 6 major GDPs with α-dicarbonyl structure as 3-deoxyglucosone, 3-deoxygalactosone, glucosone, glyoxal, methylglyoxal, and 3,4-dideoxyglucosone-3-ene. Valid quantification of these GDPs was achieved by ultrahigh-performance liquid chromatography/diode array detector/tandem mass spectrometry. Identification and quantification of single GDPs allow a structure-dependent risk evaluation. As a consequence, PD fluids and processes can be improved to reduce the GDP burden of patients undergoing PD.
Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center, University of Erlangen-Nuremberg, Erlangen, Germany.
Stefan
S
Mittelmaier
Toshimitsu
T
Niwa
Monika
M
Pischetsrieder
D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000032:analysis; D015314:Dialysis Solutions / Q000009:adverse effects / Q000737:chemistry*; D005690:Galactose / Q000031:analogs & derivatives / Q000032:analysis; D005947:Glucose / Q000737:chemistry*; D006037:Glyoxal / Q000032:analysis; D006358:Hot Temperature; D006801:Humans; D007661:Ketoses / Q000032:analysis; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D011753:Pyrones / Q000032:analysis; D013329:Structure-Activity Relationship
C504711:3,4-dideoxyglucosone-3-ene; C555526:3-deoxygalactosone; D015314:Dialysis Solutions; D007661:Ketoses; D011753:Pyrones; C017022:glucosone; D006037:Glyoxal; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D005947:Glucose; D005690:Galactose