An LC-MS/MS analytical method for the determination of uremic toxins in patients with end-stage renal disease
An LC-MS/MS analytical method for the determination of uremic toxins in patients with end-stage renal disease
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测定终末期肾病患者尿毒症毒素的 LC-MS/MS 分析方法
DOI：
10.1016/j.jpba.2020.113551
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发表时间：
2020-11-30
影响因子：
3.4
通讯作者：
Wu, Xin-an
中科院分区：
文献类型：
--
作者：
Ma, Yan-rong;Xin, Ming-yan;Wu, Xin-an
终末期肾脏疾病（ESRD）是慢性肾脏疾病的最后阶段，其特征是尿毒症毒素（UTs）的进行性积累。血液透析是从体内清除ut的标准方法。肌酐和尿素水平是血液透析效果的重要指标，但这些指标在评估ut清除，特别是蛋白结合ut清除方面的效用有限。我们开发了一种LC-MS/MS方法来定量ut，并为评估血液透析效果提供标记物。这些物质经乙腈沉淀蛋白质后从血清样品中提取，然后在HILIC柱上分离。流速为0.6 mL/min，运行时间为8.0？最小值分别为负离子模式和正离子模式。在本研究中，测定了正常受试者和血液透析前后ESRD患者的26个ut；ESRD患者的血清水平明显高于肾功能正常的受试者。透析治疗后患者血清各种UTs均显著降低，但山茱萸酸、CMPF、犬尿酸、对甲酚硫酸盐、苯基- β - d -葡萄糖醛酸盐、4-乙基苯基硫酸酯和3-吲哚基- β - d -葡萄糖苷含量无变化。这些结果表明血液透析不能完全去除一些ut。此外，还提出了一些不同类型ut的生物标志物来评估血液透析的有效性。(C) 2020 Elsevier B.V.版权所有
End-stage renal disease (ESRD) is the last stage of chronic kidney disease, characterized by the progressive accumulation of uremic toxins (UTs). Hemodialysis is the standard approach to remove UTs from the body. Creatinine and urea levels are important indices of hemodialysis effectiveness, but the utility of those markers to estimate the removal of UTs, especially protein-binding UTs is limited. We developed an LC-MS/MS method for the quantification of UTs and to provide markers for evaluating hemodialysis effectiveness. These substances were extracted from serum samples after acetonitrile precipitation of protein and then separated on a HILIC column. The flow rate was 0.6 mL/min with a run time of 8.0?min for the negative ion mode and positive ion mode each. In this study 26 UTs were determined in normal subjects and in patients with ESRD before and after hemodialysis; serum levels were significantly higher in patients with ESRD than in subjects with normal renal function. A significant decrease in a variety of serum UTs were observed in patients after dialysis treatment, but no change in the levels of orotic acid, CMPF, kynurenic acid, p-cresol sulfate, phenyl-beta-D-glucuronide, 4-ethylphenyl sulfate and 3-indolyl-beta-D-glucopyranoside was found. These results show that some UTs could not be completely removed by hemodialysis. In addition, some biomarkers of different types of UTs are proposed for evaluating hemodialysis effectiveness. (C) 2020 Elsevier B.V. All rights reserved.