title: Abnormal cyanide metabolism in uraemic patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Nagoya Daini Red Cross Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koyama
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: A
authors.initials: A
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Morozumi
authors.forename: T
authors.initials: T
authors.lastname: Fujinami
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D003486:Cyanides / Q000097:blood*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D006435:Renal Dialysis; D013861:Thiocyanates / Q000097:blood; D014511:Uremia / Q000097:blood* / Q000188:drug therapy; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D003486:Cyanides; D013861:Thiocyanates; C019476:mecobalamin; C031760:thiocyanate; D014805:Vitamin B 12