Abnormal cyanide metabolism in uraemic patients

• Published in: Nephrology, dialysis, transplantation Vol. 12; no. 8; pp. 1622 - 1628
• Main Authors: KOYAMA, K, YOSHIDA, A, TAKEDA, A, MOROZUMI, K, FUJINAMI, T, TANAKA, N
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.1997
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Cyanides - blood; Emergency and intensive care: renal failure. Dialysis management; Female; Humans; Intensive care medicine; Kidney Failure, Chronic - therapy; Male; Medical sciences; Middle Aged; Osmolar Concentration; Renal Dialysis; Thiocyanates - blood; Uremia - blood; Uremia - drug therapy; Vitamin B 12 - analogs & derivatives; Vitamin B 12 - therapeutic use; Kidney disease; Human; Extrarenal dialysis; Chronic; Urinary system disease; Hemodialysis; Risk factor; Renal failure; Cyanides; Neuropathy; Metabolism
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/12.8.1622

We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a significant relationship between the severity of vibration sensation impairment and the patients' smoking habits. The administration of methylcobalamin markedly improved the severity of uraemic neuropathy in terms of vibration perception thresholds. We presumed that abnormal cyanide metabolism is involved in the development of uraemic neuropathy. Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic renal failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients), and 13 healthy volunteers as a control group. Nine of the 30 HD patients were smokers. In addition, in 10 HD patients without smoking habits and 10 non-smoking healthy volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was estimated. The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non-smoking HD patients was identical to that in the PCRF group, whereas the level in the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN- levels were lower than in those without methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction was low. And the serum cyanocobalamin level was higher in the treated subgroup. In uraemic patients, cyanide detoxication capability is impaired because of a reduced SCN- clearance, and increased cyanocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy. Methylcobalamin was considered to be utilized in cyanide detoxication process via cyanocobalamin synthesis.