Evidence of altered homocysteine metabolism in chronic renal failure

The fasting serum concentrations of total homocysteine and metabolites of t ranssulfuration (cystathionine, cysteine, methylmalonic acid, 2-methylcitri c acid) and remethylation (methionine) were determined by gas chromatograph y-mass spectrometry in 40 nondialyzed patients with chronic renal disease a nd in 50 patients with end-stage renal disease requiring chronic maintenanc e hemodialysis. The nondialyzed patients and 28 of the dialysis patients di d not receive additional vitamin supplementations. Twenty-two of the dialys is patients received daily oral vitamin preparations containing 10 mg pyrid oxine (vitamin B-6), 6 mu g cyanocobalamin (vitamin B-12), and 1 mg folic a cid. In the nondialyzed patients, linear regression analysis showed positiv e correlations between serum concentrations of creatinine and total homocys teine (r = 0.68, p < 0.0001), cystathionine (r = 0.73, p < 0.0001), methylm alonic acid (r = 0.77, p < 0.0001), and 2-methylcitric acid (r = 0.81, p < 0.0001). Serum homocysteine was positively correlated with serum concentrat ions of cystathionine (r = 0.59, p < 0.0001), cysteine (r = 0.69, p = 0.004 ), methylmalonic acid (r = 0.64, p = 0.0001), and 2-methylcitric acid (r = 0.64, p < 0.0001). There was no significant correlation between serum conce ntrations of homocysteine and methionine (r = -0.14, p = 0.63). In the hemo dialysis patients receiving oral vitamin supplementation, serum homocystein e and cystathionine concentrations were significantly lower than in hemodia lysis patients not receiving vitamins (homocysteine 21.8 +/- 1.1 vs. 33.2 /- 3.7 mu mol/l, p 0.0004; cystathionine 2,075.9 +/- 387.1 vs. 3,171.3 +/- 680.2 nmol/l, p = 0.02; mean +/- SEM). In summary, our results show increas ed intermediate products of the transsulfuration pathway, but no increase i n remethylation of homocysteine in chronic renal disease, including end-sta ge renal disease requiring chronic maintenance dialysis. Copyright (C) 1999 S. Karger AG, Basel.