Affinity adsorption of glucose degradation products improves the biocompatibility of conventional peritoneal dialysis fluid.
BACKGROUND
Reactive carbonyl compounds (RCOs) present in peritoneal dialysis (PD) fluid have been incriminated in the progressive deterioration of the peritoneal membrane in long-term PD patients. They are initially present in fresh conventional heat-sterilized glucose PD fluid and are supplemented during dwell time by the diffusion of blood RCOs within the peritoneal cavity. In the present study, RCO entrapping agents were immobilized on affinity beads to adsorb RCOs both in fresh PD fluid and in PD effluent.


METHODS
The RCO trapping potential of various compounds was assessed in vitro first by dissolving them in the tested fluid and subsequently after coupling with either epoxy- or amino-beads. The tested fluids include fresh heat-sterilized glucose and non-glucose PD fluids, and PD effluent. Their RCOs contents, that is, glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG), formaldehyde, 5-hydroxymethylfuraldehyde, acetaldehyde, and 2-furaldehyde were monitored by reverse-phase high-pressure liquid chromatography. The biocompatibility of PD fluid was assessed by a cytotoxic assay with either human epidermoid cell line A431 cells or with primary cultured human peritoneal mesothelial cells.


RESULTS
Among the tested RCO entrapping agents, hydrazine coupled to epoxy-beads proved the most efficient. It lowered the concentrations of three dicarbonyl compounds (GO, MGO, and 3-DG) and those of aldehydes present in fresh heat-sterilized glucose PD fluid toward the low levels observed in filter-sterilized glucose PD fluid. It did not change the glucose and electrolytes concentration of the PD fluid but raised its pH from 5.2 to 5.9. Hydrazine-coupled epoxy-bead also lowered the PD effluent content of total RCOs, measured by the 2,4-dinitrophenylhydrazone (DNPH) method. The cytotoxicity of heat-sterilized PD fluid incubated with hydrazine-coupled epoxy-beads was decreased to the level observed in filter-sterilized PD fluid as the result of the raised pH and the lowered RCOs levels.


CONCLUSIONS
Hydrazine-coupled epoxy-beads reduce the levels of a variety of dicarbonyls and aldehydes present in heat-sterilized glucose PD fluid to those in filter-sterilized PD fluid, without altering glucose, lactate, and electrolytes contents but with a rise in pH. Incubated with PD effluents, it is equally effective in reducing the levels of serum-derived RCOs. RCO entrapping agents immobilized on affinity beads improve in vitro the biocompatibility of conventional heat-sterilized glucose PD fluid. Their clinical applicability requires further studies.
Ishikawa
Naoyoshi
N
Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Miyata
Toshio
T
Ueda
Yasuhiko
Y
Inagi
Reiko
R
Izuhara
Yuko
Y
Yuzawa
Hiroko
H
Onogi
Hiroshi
H
Nishina
Makoto
M
Nangaku
Masaomi
M
Van Ypersele De Strihou
Charles
C
Kurokawa
Kiyoshi
K
D000447:Aldehydes / Q000378:metabolism; D004852:Epoxy Compounds; D005947:Glucose / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008422:Materials Testing; D008863:Microspheres; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000378:metabolism; D016060:Sorption Detoxification
D000447:Aldehydes; D004852:Epoxy Compounds; D006146:Guanidines; D006834:Hydrazines; C029424:hydrazine; C070130:diaminoguanidine; D005947:Glucose