Mettang T, Thomas S, Kiefer T, Fischer F P, Kuhlmann U, Wodarz R, Rettenmeier A W
Robert Bosch Hospital, Department of Internal Medicine, Stuttgart, Germany.
Perit Dial Int. 1996 Jan-Feb;16(1):58-62.
To evaluate the degree of exposure to and the fate of di(2-ethylhexyl)phthalate (DEHP) and its major derivatives mono(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH), and phthalic acid (PA) in patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) during a 4-hour dwell period.
Prospective, controlled.
Teaching hospital, Department of Nephrology.
Seven elderly patients on stable CAPD using Fresenius instruments and dialysate and 6 age-matched healthy controls.
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.
Quantitative analysis of DEHP 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.
Serum concentrations of DEHP and PA were significantly higher in patients (median: 0.079 microgram/mL, range: 0.032-0.210 microgram/mL; and 0.167 microgram/mL, range: 0.097-0.231 microgram/mL, respectively) than in controls [0.0195 microgram/mL, range: 0.016-0.025 microgram/mL (p = 0.0027) and 0.0120 microgram/mL, range: 0.006-0.034 microgram/mL (p = 0.0026), respectively]. Concentration of MEHP 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 MEHP and 2-EH in dialysate consistently decreased from 0.177 (range: 0.137-0.239 microgram/mL) to 0.022 microgram/mL (range: 0.005-0.058 microgram/mL) (p = 0.017), and from 0.087 (range: 0.075-0.097 microgram/mL) to 0.05 microgram/mL (range: 0.023-0.064 microgram/mL) (p = 0.017), respectively, while the concentration of DEHP remained stable. Remarkably high concentrations of PA (0.129 microgram/mL; range: 0.038-0.466 microgram/mL) were found in CAPD bags prior to use, and these concentrations tended to increase during dwell time, without statistical significance, however (0.135 microgram/mL; range: 0.073-0.659 microgram/mL, p = 0.062).
Patients on CAPD are regularly exposed to considerable amounts of phthalic ester derivatives, mainly to MEHP and PA. MEHP seems to be well absorbed by the peritoneal membrane. The long-term effects of this exposure remain to be elucidated.
评估接受规律持续性非卧床腹膜透析(CAPD)的患者在4小时留腹期间邻苯二甲酸二(2-乙基己基)酯(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)的暴露程度及转归情况。
前瞻性对照研究。
教学医院肾内科。
7例使用费森尤斯仪器和透析液进行稳定CAPD治疗的老年患者以及6例年龄匹配的健康对照者。
在常规进行的腹膜平衡试验(PET)期间,留腹开始前、开始后120分钟和240分钟采集血液和透析液样本。此外,从一组参与药物研究的志愿者中采集血样。
采用选择离子监测气相色谱/质谱联用技术,在质谱仪的正离子和负离子化学电离模式下对DEHP及其水解产物进行定量分析。
患者血清中DEHP和PA的浓度显著高于对照组(中位数分别为:0.079微克/毫升,范围:0.032 - 0.210微克/毫升;以及0.167微克/毫升,范围:0.097 - 0.231微克/毫升),对照组分别为[0.0195微克/毫升,范围:0.016 - 0.025微克/毫升(p = 0.0027)和0.0120微克/毫升,范围:0.006 - 0.034微克/毫升(p = 0.0026)]。使用前CAPD袋中MEHP的浓度比母体化合物高4倍。在留腹的前4小时内,透析液中MEHP和2-EH的浓度持续下降,分别从0.177(范围:0.137 - 0.239微克/毫升)降至0.022微克/毫升(范围:0.005 - 0.058微克/毫升)(p = 0.017),以及从0.087(范围:0.075 - 0.097微克/毫升)降至0.05微克/毫升(范围:0.023 - 0.064微克/毫升)(p = 0.017),而DEHP的浓度保持稳定。使用前CAPD袋中PA的浓度显著较高(0.129微克/毫升;范围:0.038 - 0.466微克/毫升),且这些浓度在留腹期间有升高趋势,但无统计学意义(0.135微克/毫升;范围:0.073 - 0.659微克/毫升,p = 0.062)。
CAPD患者经常接触大量邻苯二甲酸酯衍生物,主要是MEHP和PA。MEHP似乎能被腹膜很好地吸收。这种暴露的长期影响仍有待阐明。