Carbonyl Stress Reduction in Peritoneal Dialysis Fluid: Development of a Novel High-Affinity Adsorption Bead

Abstract

Heat sterilization of glucose peritoneal dialysis (PD) fluid generates reactive carbonyl compounds (RCOs), which have been implicated in the formation of advanced glycation end products (AGEs) on peritoneal proteins, with an attendant deterioration of peritoneal permeability in PD patients. To reduce their levels in PD fluid, we had previously devised beads coupled with RCO-trapping agents. The hazards linked to the diffusion of RCO-trapping compounds in the systemic circulation are avoided. Hydrazine-epoxy beads proved the most effective. Still, the amount needed to trap all RCOs remained relatively large. We developed a novel agent linking a powerful RCO-trapping AGE inhibitor, pyrazolinone-polyethyleneimine, with cellulose beads (PPCBs). We tested its effectiveness to lower RCOs and AGE formation. Mixed with glucose PD fluid, PPCBs markedly lowered RCOs (alpha-dicarbonyls and aldehydes) and inhibited the generation of pentosidine, an AGE, to levels similar to those of filter-sterilized PD fluid. Their effectiveness is more than one order of magnitude above those of previously developed beads. The PPCBs markedly improved PD fluid biocompatibility. Incubation of 1 L commercial glucose PD fluid at 25 degrees C for 24 hours with 10 or 30 g of wet PPCBs reduced RCO content by 75% - 90% and 100% respectively, without altering the pH or glucose and electrolyte contents of the PD fluid. We developed a high-affinity adsorption bead to reduce the toxic RCO content and AGE formation potential (carbonyl stress) of PD fluid.