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 dwel l time, and their role in the formation of advanced glycation end-products (AGEs). Measurements: Dicarbonyl compounds in heat- and filter-sterilized PD fluids were quantified by reverse-phase high performance liquid chromatography (H PLC) 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). Patients: AGEs and dicarbonyl compounds were measured in effluents collecte d from standardized 4-hour dwells from 8 continuous cycling peritoneal dial ysis patients. Results: In PD fluids, 3-deoxyglucosone (3-DG) has been identified as the m ajor dicarbonyl compound formed during the process of heat sterilization. T he process also formed glyoxal (GO) and methylglyoxal (MGO), with the amoun t of 3-DG being approximately 25 - 60 times higher than GO and MGO. When in cubated with albumin, the identified 1,2-dicarbonyl compounds rapidly forme d AGEs. The formation of AGEs was more pronounced in conventional heat-ster ilized PD fluids compared with filter-sterilized PD fluids, and was complet ely inhibited by aminoguanidine. In effluents, the concentration of MGO, GO , and 3-DG decreased with increasing dwell time, with a concomitant increas e in AGE fluorescence. Conclusions: The dicarbonyl compounds 3-DG, MGO, and GO are potent promoter s of AGE formation. The presence of these and possibly other dicarbonyl com pounds formed during heat sterilization of glucose-based PD fluids is, to a large extent, responsible for the in vitro AGE formation by these fluids, as evidenced by the speed of AGE formation in PD fluids and the complete in hibition by aminoguanidine. Because 3-DG, MGO, and GO ave rapidly cleared f rom PD fluids during dialysis, these compounds may contribute to the in viv o AGE formation in PD patients.