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血液透析患者中氰化物和硫氰酸盐的蓄积

Accumulation of cyanide and thiocyanate in haemodialysis patients.

作者信息

Hasuike Yukiko, Nakanishi Takeshi, Moriguchi Rintarou, Otaki Yoshinaga, Nanami Masayoshi, Hama Yasue, Naka Miki, Miyagawa Koji, Izumi Masaaki, Takamitsu Yoshihiro

机构信息

Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.

出版信息

Nephrol Dial Transplant. 2004 Jun;19(6):1474-9. doi: 10.1093/ndt/gfh076. Epub 2004 Feb 19.

Abstract

BACKGROUND

Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients.

METHODS

We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate.

RESULTS

Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed.

CONCLUSIONS

The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.

摘要

背景

氰化物是一种有毒物质,其解毒产物硫氰酸盐可能是尿毒症的主要致病物质。最近对髓过氧化物酶(MPO)/硫氰酸盐系统的研究表明硫氰酸盐与动脉粥样硬化之间存在联系。然而,传统的氰化物和硫氰酸盐检测方法存在误差,限制了我们对血液透析(HD)患者中它们代谢情况的了解。

方法

我们使用高效液相色谱法测量了43例HD患者红细胞中的氰化物和血浆中的硫氰酸盐,以及包括15名当前吸烟者在内的46名健康对照者的上述指标。为了阐明尿毒症患者中氰化物向硫氰酸盐的代谢转化,我们还测量了半胱氨酸和硫酸盐。然后,我们使用逐步回归分析来分析决定红细胞氰化物和血浆硫氰酸盐的因素。

结果

HD患者的平均氰化物和硫氰酸盐水平显著高于非吸烟对照者。然而,透析患者的氰化物水平远低于致死浓度。HD患者的硫氰酸盐水平比非吸烟对照者高6至7倍,透析后硫氰酸盐的下降仅为19.3±3.5%。多元回归分析显示,对照者中氰化物与硫氰酸盐呈正相关,而HD患者中呈负相关。在患者中,还观察到硫氰酸盐与尿素氮之间呈负相关。

结论

透析患者硫氰酸盐水平升高可能继发于HD效率有限以及氰化物和硫氰酸盐代谢紊乱。由于硫氰酸盐是MPO的首选底物,它可能在包括心血管事件在内的尿毒症并发症中起作用。

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