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Uraemic pruritus is a frequent and disabling symptom in patients on dialysis. The pathogenesis of uraemic pruritus is nevertheless still obscure. We investigated whether di(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in polyvinylchloride (PVC) haemodialysis tubings, is a possible pathogenetic factor in uraemic pruritus. Serum concentrations of DEHP and its major derivatives mono-(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH) and phthalic acid (PA) were determined in uraemic patients before and after a haemodialysis session and compared with the occurrence and intensity of pruritus in these patients. Twenty-one patients on regular haemodialysis for at least 6 months were examined. The severity of uraemic pruritus was assessed using a standard questionnaire (pruritus score). The quantitative analysis of DEHP and its derivatives was carried out by GC/selected ion monitoring mass spectrometry. Fourteen out of 21 patients (66%) complained about uraemic pruritus to a variable degree. The post-dialysis serum concentrations of DEHP, MEHP and 2-EH were significantly higher than the corresponding pre-dialysis values, whereas the post-dialysis concentrations of PA (0.122 +/- 0.078 microgram/microliter) were significantly lower than pre-dialysis levels (0.194 +/- 0.101 microgram/microliter, P = 0.00068). Neither pre- nor post-dialysis serum concentrations of DEHP, MEHP, PA or 2-EH were correlated with the severity of uraemic pruritus. Additionally, serum concentrations of DEHP and its metabolites did not differ significantly in patients with and without pruritus. These findings suggest that patients on haemodialysis are regularly exposed to considerable amounts of DEHP and metabolites. Phthalic acid, one of the presumed end products of DEHP metabolism, might be eliminated at least in part by haemodialysis. The exposition to DEHP and metabolites during haemodialysis, as assessed by measuring serum concentrations, bears no immediate relation to the occurrence or intensity of uraemic pruritus.

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Objectives To evaluate the impact of a plasticizer-free device on exposure to di-(2-ethylhexyl) phthalate (DEHP) and its major metabolites in patients on continuous ambulatory peritoneal dialysis (CAPD). DEHP is the most commonly used plasticizer in polyvinyl chloride (PVC) products; it is added to CAPD bags in order to improve the flexibility of the material. Since DEHP leaches out of the plastic matrix, patients on CAPD are exposed to considerable amounts of DEHP and its metabolites. Design A prospective cross-over study. Setting Department of nephrology in a teaching hospital. Participants Six patients (4 female, 2 male) stable on peritoneal dialysis (PD) for at least 6 months. Interventions Patients were switched from a plasticizer-containing PVC CAPD system (A.N.D.Y. Plus, Fresenius Medical Care, Bad Homburg, Germany) to a polyolefine-made plasticizer-free system (stay-safe, Fresenius). Main Outcome Measures Prior to and 42 days after the switch, 24-hour effluent dialysate and urine collections were performed and 10 mL blood was drawn. Concentrations of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) in urine, dialysate, and serum were determined using gas chromatography/mass spectrometry. Results Complete data were obtained from 5 patients. Serum levels of PA decreased significantly during the study period (0.137 ± 0.078 mg/L vs 0.124 ± 0.049 mg/L, p = 0.04), and the respective levels of DEHP decreased insignificantly (0.097 ± 0.076 mg/L vs 0.069 ± 0.046 mg/L, p = 0.07), whereas the concentrations of MEHP and 2-EH remained unchanged. Urine concentrations of PA were high (0.81 ± 0.69 mg/L) but did not change substantially (0.70 ± 0.50 mg/L). Effluent dialysate concentrations of MEHP and PA decreased significantly (0.0176 ± 0.004 mg/L vs 0.0040 ± 0.0007 mg/L, p = 0.043 and 0.158 ± 0.056 mg/L vs 0.111 ± 0.051 mg/L, p = 0.043, respectively). Conclusions Although PD patients seem to be exposed to other sources of phthalates in addition to dialysis, use of plasticizer-free devices may help to reduce potentially immunosuppressive exposure to phthalate esters.

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.