ABNORMAL CYANIDE METABOLISM IN UREMIC PATIENTS

Background. We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a s ignificant relationship between the severity of vibration sensation im pairment and the patients' smoking habits. The administration of methy lcobalamin markedly improved the severity of uraemic neuropathy in ter ms of vibration perception thresholds. We presumed that abnormal cyani de metabolism is involved in the development of uraemic neuropathy. Me thods. Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic rena l failure (PCRF), 30 patients undergoing regular haemodialysis (HD pat ients), and 13 healthy volunteers as a control group, Nine of the 30 H D patients were smokers, In addition, in 10 HD patients without smokin g habits and 10 non-smoking healthy volunteers? the proportion of each vitamin B-12 analogue in total vitamin B-12 was estimated. Results. T he mean serum SCN-level of the 12 PCRF patients (5.1 +/- 1.5 mu g/ml) was significantly higher than that of the control (2.8 +/- 0.9 mu g/ml ) (P<0.01). The mean SCN-level before haemodialysis in the 21 nonsmoki ng HD patients was identical to that in the PCRF group, whereas the le vel in the nine smoking HD patients (7.2 +/- 1.8 mu g/ml) significantl y higher than that in the non-smoking subgroup (P<0.01). In 16 HD pati ents with methylcobalamin treatment, serum SCN-levels were lower than in those without methylcobalamin treatment (4.5+/-0.5 mu g/ml in non-s moking subgroup: P<0.05). And in the methylcobalamin-treated subgroup (n=5), the proportion of each vitamin B-12 analogue in total vitamin B -12 was normal. In the untreated subgroup (n=5), the proportion of cya nocobalamin fraction (10.5+/-2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction wa s low. And the serum cyanocobalamin level was higher in the treated su bgroup. Conclusion. In uraemic patients, cyanide detoxication capabili ty is impaired because of a reduced SCN- clearance, and increased cyan ocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy, Methylcobalamin w as considered to be utilized in cyanide detoxication process via cyano cobalamin synthesis.