Abstract
Heat sterilization of peritoneal dialysis fluids (PDFs) leads to the formation of glucose degradation products (GDPs), which impair long-term peritoneal dialysis. The current study investigated the effects of metal ions, which occur as trace impurities in the fluids, on the formation of six major α-dicarbonyl GDPs, namely glucosone, glyoxal, methylglyoxal, 3-deoxyglucosone, 3-deoxygalactosone, and 3,4-dideoxyglucosone-3-ene. The chelation of metal ions by 2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid (DTPA) during sterilization significantly decreased the total GDP content (585 μM vs. 672 μM), mainly due to the decrease of the glucose-oxidation products glucosone (14 μM vs. 61 μM) and glyoxal (3 μM vs. 11 μM), but also of methylglyoxal (14 μM vs. 31 μM). The glucose-dehydration products 3-deoxyglucosone, 3-deoxygalactosone, and 3,4-dideoxyglucosone-3-ene were not significantly affected by chelation of metal ions. Additionally, PDFs were spiked with eleven different metal ions, which were detected as traces in commercial PDFs, to investigate their influence on GDP formation during heat sterilization. Iron(II), manganese(II), and chromium(III) had the highest impact increasing the formation of glucosone (1.2–1.5 fold increase) and glyoxal (1.3–1.5 fold increase). Nickel(II) and vanadium(III) further promoted the formation of glyoxal (1.3 fold increase). The increase of the pH value of the PDFs from pH 5.5 to a physiological pH of 7.5 resulted in a decreased formation of total GDPs (672 μM vs 637 μM). These results indicate that the adjustment of metal ions and the pH value may be a strategy to further decrease the content of GDPs in PDFs.
Highlights
Reactive glucose degradation products (GDPs) are of high relevance for the production of glucose-containing drugs
The main purpose of the present study was to investigate the impact of inorganic cations, which are observed as impurities in peritoneal dialysis fluids (PDFs), on the heat-induced formation of the six major αdicarbonyl GDPs in PDFs
To quantify any GDPs introduced by the matrix, unheated aliquots of all PDFs were screened for α-dicarbonyls
Summary
Reactive glucose degradation products (GDPs) are of high relevance for the production of glucose-containing drugs Products such as peritoneal dialysis fluids (PDFs) or infusion solutions are heat-sterilized to ensure the microbiological safety. Changes in membrane morphology, membrane thickening, and a declining ultrafiltration capacity of the peritoneal membrane were associated with a high GDP load in PDFs and AGE formation [11,12,13,14]. These complications can eventually cause the discontinuation of this renal replacement therapy
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