The Fate of Leached Di(2-Ethylhexyl)Phthalate in Patients Undergoing Capd Treatment

Abstract

Objectives To evaluate the degree of exposure to and the fate of di(2-ethylhexyl)phthalate (DE HP) and its major derivatives mono(2-ethylhexyl)phthalate (ME HP), 2-ethylhexanol (2-EH), and phthalic acid (PA) in patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) during a 4-hour dwell period. Design Prospective, controlled. Setting Teaching hospital, Department of Nephrology. Participants Seven elderly patients on stable CAPD using Fresenius instruments and dialysate and 6 agematched healthy controls. Interventions During a routinely performed peritoneal equilibration test (PET), blood and dialysate samples were drawn before and 120 and 240 min after the dwell was started. In addition, blood samples were taken from a group of volunteers participating in a pharmacological study. Measurements Quantitative analysis of DE HP and its hydrolysis products was performed by selected ion-monitoring gas chromatography/mass spectrometry, operating the mass spectrometer in a combined positive and negative ion chemical ionization mode. Results Serum concentrations of DE HP and PA were significantly higher in patients (median: 0.079 I1g/mL, range: 0.032 -0.210 I1g/mL; and 0.167 I1g/mL, range: 0.097 0.231 I1g/mL, respectively) than in controls [0.0195 I1g/mL, range: 0.016 -0.025I1g/mL (p = 0.0027) and 0.0120 I1g/mL, range: 0.006 -0.034I1g/mL (p = 0.0026), respectively]. Concentration of ME HP in the fluid of CAPD bags prior to use was four times higher than that of the parent compound. During the first 4 hours of dwell time, the concentrations of ME HP and 2-EH in dialysate consistently decreased from 0.177 (range: 0.137 -0.239119/ mL) to 0.022 I1g/mL (range: 0.005 -0.058 I1g/mL) (p = 0.017), and from 0.087 (range: 0.075 -0.097I1g/mL) to 0.05 I1g/mL (range: 0.023 0.064I1g/mL) (p = 0.017), respectively, while the concentration of DE HP remained stable. Remarkably high concentrations of PA (0.129 I1g/mL; range: 0.038 -0.466 I1g/mL) were found in CAPD bags prior to use, and these concentrations tended to increase during dwell time, without statistical significance, however (0.135I1g/mL; range: 0.073 -0.659I1g/mL, p = 0.062). Conclusions Patients on CAPD are regularly exposed to considerable amounts of phthalic ester derivatives, mainly to MEHPand PA. ME HP seems to bewellabsorbed by the peritoneal membrane. The long-term effects of this exposure remain to be elucidated.