Homocysteine (tHcy) is a risk factor for
atherosclerosis in patients with
end-stage renal disease and
chronic renal insufficiency (CRI).
Vitamin B6 deficiency may result in high tHcy levels, especially after a
methionine load (PML). Therefore, we evaluated
vitamin B6 metabolism and tHcy (fasting and PML) levels in patients with CRI and those on
hemodialysis (HD)
therapy before and during high-dose sequential
vitamin B6 and
folic acid supplementation in male patients (27 patients, HD, 17 patients, CRI) and 19 age-matched healthy controls.
Vitamin B6 doses were 100 mg/d in patients with CRI and 200 mg/d in HD patients, plus
folic acid (5 mg/d), for more than 3 months in each period. We analyzed
vitamin B6 metabolites by high-performance liquid chromatography in plasma and red blood cells (RBCs) and fasting tHcy in all cases and PML in subgroups of 11 HD patients and 14 patients with CRI. We found
vitamin B6 deficiency and high tHcy (fasting and PML) levels in all patients. Plasma and RBC levels of
pyridoxal and
pyridoxal phosphate were abnormally low, whereas levels of
pyridoxic acid (PA), an end product of
vitamin B6 metabolism, were extremely high in both groups. Fasting and PML tHcy levels were partially resistant to
vitamin B6 supplements, with different response patterns in HD patients and those with CRI. Thus, the PML defect was more responsive to
folic acid in HD patients, whereas
vitamin B6 partially reduced PML tHcy levels in patients with CRI. Resistance of tHcy to
vitamin B6 treatment in patients with CRI and HD patients is not caused by poor absorption or low tissue stores. Rather, nonvitamin factors or potentially toxic PA levels may be implicated in abnormal
vitamin B6 and/or tHcy metabolism during
renal insufficiency.