Mettang T, Thomas S, Kiefer T, Fischer F P, Kuhlmann U, Wodarz R, Rettenmeier A W
Robert-Bosch-Krankenhaus, Department of Internal Medicine, Stuttgart, Germany.
Nephrol Dial Transplant. 1996 Dec;11(12):2439-43. doi: 10.1093/oxfordjournals.ndt.a027211.
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.
尿毒症瘙痒是透析患者常见且令人不适的症状。然而,尿毒症瘙痒的发病机制仍不清楚。我们研究了聚氯乙烯(PVC)血液透析管路中最常用的增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)是否可能是尿毒症瘙痒的致病因素。测定了尿毒症患者血液透析前后血清中DEHP及其主要衍生物单-(2-乙基己基)邻苯二甲酸酯(MEHP)、2-乙基己醇(2-EH)和邻苯二甲酸(PA)的浓度,并与这些患者瘙痒的发生情况和严重程度进行比较。对21例接受规律血液透析至少6个月的患者进行了检查。使用标准问卷(瘙痒评分)评估尿毒症瘙痒的严重程度。通过气相色谱/选择离子监测质谱法对DEHP及其衍生物进行定量分析。21例患者中有14例(66%)不同程度地抱怨有尿毒症瘙痒。透析后血清中DEHP、MEHP和2-EH的浓度显著高于相应的透析前值,而透析后PA的浓度(0.122±0.078微克/微升)显著低于透析前水平(0.194±0.101微克/微升,P = 0.00068)。透析前和透析后血清中DEHP、MEHP、PA或2-EH的浓度均与尿毒症瘙痒的严重程度无关。此外,有瘙痒和无瘙痒患者血清中DEHP及其代谢产物的浓度无显著差异。这些发现表明,血液透析患者经常接触大量的DEHP及其代谢产物。邻苯二甲酸是DEHP代谢的假定终产物之一,可能至少部分通过血液透析被清除。通过测量血清浓度评估,血液透析过程中接触DEHP及其代谢产物与尿毒症瘙痒的发生或严重程度没有直接关系。