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Perit Dial Int 27(3): 300-308 2007
© 2007 International Society for Peritoneal Dialysis
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Bench

CARBONYL STRESS REDUCTION IN PERITONEAL DIALYSIS FLUID: DEVELOPMENT OF A NOVEL HIGH-AFFINITY ADSORPTION BEAD

Makoto Yamamoto1, Yuko Izuhara1, Takatoshi Kakuta1, Shunya Takizawa1, Akio Fujita2, Tatsuhiko Higaki2, Charles van Ypersele de Strihou3 and Toshio Miyata1

1 Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa; 2 Kuraray Research Laboratories, Okayama, Japan; 3 and Service de Nephrologie, Universite Catholique de Louvain, Brussels, Belgium

Correspondence to: T. Miyata, Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
t-miyata{at}is.icc.u-tokai.ac.jp

{diamondsuit} Objective: 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.

{diamondsuit} Methods: 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.

{diamondsuit} Results: 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°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.

{diamondsuit} Conclusions: We developed a high-affinity adsorption bead to reduce the toxic RCO content and AGE formation potential (carbonyl stress) of PD fluid.

KEY WORDS: KEY WORDS:; Glucose degradation product; carbonyl stress; reactive carbonyl compound; advanced glycation end product; adsorption bead.

Received 21 November 2006; accepted 7 February 2007.






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