Induction of 1,2-dicarbonyl compounds, intermediates in the formation of advanced glycation end-products, during heat-sterilization of glucose-based peritoneal dialysis fluids.
OBJECTIVE
To study the presence of 1,2-dicarbonyl compounds in peritoneal dialysis (PD) fluids, their concentration in effluents with increasing dwell time, and their role in the formation of advanced glycation end-products (AGEs).


METHODS
Dicarbonyl compounds in heat- and filter-sterilized PD fluids were quantified by reverse-phase high performance liquid chromatography (HPLC) after derivatization to dimethoxyquinoxaline derivatives. Kinetics of the in vitro formation of AGEs upon incubation of 1,2-dicarbonyl compounds or PD fluids with albumin, with or without aminoguanidine, were measured by AGE fluorescence (excitation/emission wavelengths of 350 nm/430 nm).


METHODS
AGEs and dicarbonyl compounds were measured in effluents collected from standardized 4-hour dwells from 8 continuous cycling peritoneal dialysis patients.


RESULTS
In PD fluids, 3-deoxyglucosone (3-DG) has been identified as the major dicarbonyl compound formed during the process of heat sterilization. The process also formed glyoxal (GO) and methylglyoxal (MGO), with the amount of 3-DG being approximately 25-60 times higher than GO and MGO. When incubated with albumin, the identified 1,2-dicarbonyl compounds rapidly formed AGEs. The formation of AGEs was more pronounced in conventional heat-sterilized PD fluids compared with filter-sterilized PD fluids, and was completely inhibited by aminoguanidine. In effluents, the concentration of MGO, GO, and 3-DG decreased with increasing dwell time, with a concomitant increase in AGE fluorescence.


CONCLUSIONS
The dicarbonyl compounds 3-DG, MGO, and GO are potent promoters of AGE formation. The presence of these and possibly other dicarbonyl compounds formed during heat sterilization of glucose-based PD fluids is, to a large extent, responsible for the in vitroAGE formation by these fluids, as evidenced by the speed of AGE formation in PD fluids and the complete inhibition by aminoguanidine. Because 3-DG, MGO, and GO are rapidly cleared from PD fluids during dialysis, these compounds may contribute to the in vivo AGE formation in PD patients.
Schalkwijk
C G
CG
Department of Clinical Chemistry, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Posthuma
N
N
ten Brink
H J
HJ
ter Wee
P M
PM
Teerlink
T
T
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000032:analysis; D015314:Dialysis Solutions / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000737:chemistry*; D006037:Glyoxal / Q000032:analysis; D006358:Hot Temperature; D006801:Humans; D010530:Peritoneal Dialysis; D011765:Pyruvaldehyde / Q000032:analysis; D013242:Sterilization
D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D006037:Glyoxal; D011765:Pyruvaldehyde; D003847:Deoxyglucose; C016350:3-deoxyglucosone