Accumulation of cyanide and thiocyanate in haemodialysis patients.
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.
Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.
Yukiko
Y
Hasuike
Takeshi
T
Nakanishi
Rintarou
R
Moriguchi
Yoshinaga
Y
Otaki
Masayoshi
M
Nanami
Yasue
Y
Hama
Miki
M
Naka
Koji
K
Miyagawa
Masaaki
M
Izumi
Yoshihiro
Y
Takamitsu
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003486:Cyanides / Q000378:metabolism*; D003545:Cysteine / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D006435:Renal Dialysis; D013861:Thiocyanates / Q000378:metabolism*; D013885:Thiosulfates / Q000378:metabolism
D003486:Cyanides; D013861:Thiocyanates; D013885:Thiosulfates; D003545:Cysteine; C031760:thiocyanate