Uraemic pruritus and exposure to di(2-ethylhexyl)phthalate (DEHP) in haemodialysis patients

Abstract

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.

Uremic Pruritus – An Update

“…Neither patients nor healthy subjects reacted positively to patch tests [60]. Another study found that patients on HD are regularly exposed to considerable amounts of DEHP (plasticizer used in polyvinylchloride HD tubings), but no immediate relation to the occurrence or intensity of uremic pruritus was found [61].…”

Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers.

“…However, because phthalates are usual laboratory contaminants, human studies using the parent phthalates as biomarkers of exposure have been primarily limited to highly exposed populations (Ching et al 1981;Dirven et al 1993;Faouzi et al 1999;Mettang et al 1996;Pollack et al 1985). In 2000, we reported a novel approach, which uses phthalate monoester metabolites as biomarkers of exposure to phthalates (Blount et al 2000a).…”

4-Heptanone is a metabolite of the plasticizer di(2-ethylhexyl) phthalate (DEHP) in haemodialysis patients

“…Heating of the stir bar released the extracted compounds into a GC-MS system for subsequent analysis in SIM mode. Analysis of MEHP in the infusates was done as their trimethylsilyl derivatives by GC-MS [21]. Briefly, mono(n-octyl)phthalate was used as internal standard and GC-MS analysis was performed in SIM mode.…”