Removal of p-cresol sulfate by hemodialysis
Removal of p-cresol sulfate by hemodialysis
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DOI：
10.1681/asn.2005030310
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发表时间：
2005-11-01
影响因子：
13.6
通讯作者：
Meyer, TW
中科院分区：
文献类型：
--
作者：
Martinez, AW;Recht, NS;Meyer, TW
蛋白质结合的溶质通过透析清除较差。这些溶质中研究最广泛的是对甲酚，其在体外已被证明是有毒的。本研究检查了对甲酚循环的形式，并通过血液透析对其清除进行了量化。血液透析患者血浆的HPLC分析含有一个峰，其迁移率对应于合成的对甲酚硫酸盐（PCS），但没有检测到未结合的对甲酚。用硫酸酯酶处理导致该峰以对甲酚形式回收，确认了其同一性。随后的研究比较了PCS和另一种蛋白结合溶质Indican的清除与临床血液透析治疗期间尿素的清除。PCS和indican与血浆蛋白的结合率分别为94 +/- 1%和93 +/- 2%。蛋白质结合导致可预测的透析清除率降低，PCS平均为20 +/- 4 ml/min，靛聚糖平均为25 +/- 5 ml/min，而尿素平均为260 +/- 20 ml/min。蛋白结合溶质的分布范围大于血浆体积，PCS平均为15 +/- 7 L，靛聚糖平均为14 +/- 3 L，尿素平均为37 +/- 7 L。PCS的溶质减少率为20 +/- 9%，靛聚糖为30 +/- 7%，尿素为69 +/- 5%。我们得出结论，对甲酚循环的形式，其硫酸盐共轭，PCS。血液透析对PCS的清除率很差，因为其清除率受蛋白结合的限制，并且其分布容积与清除率之比很高。
Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. PCS and indican were 94 +/- 1% and 93 +/- 2% bound to plasma protein, respectively. Protein-binding caused a predictable decrease in measured dialytic clearance, which averaged 20 +/- 4 ml/min for PCS and 25 +/- 5 ml/min for indican as compared with 260 +/- 20 ml/min for urea. Volumes of distribution for the protein-bound solutes were greater than the plasma volume, averaging 15 +/- 7 L for PCS and 14 +/- 3 L for indican as compared with 37 +/- 7 for urea. Solute reduction ratios were 20 +/- 9% for PCS, 30 +/- 7% for indican, and 69 +/- 5% for urea. We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS. PCS is poorly removed by hemodialysis because its clearance is limited by protein binding and the ratio of its volume of distribution to its clearance is high.