Vitamin B6 metabolism and homocysteine in end-stage renal disease and chronic renal insufficiency.
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.
Lindner
Armando
A
Department of Medicine, Veteran's Affairs Puget Sound Health Care System, University of Washington, Seattle, WA 98108, USA. lindner@u.washington.edu
Bankson
Daniel D
DD
Stehman-Breen
Catherine
C
Mahuren
J Dennis
JD
Coburn
Stephen P
SP
D000368:Aged; D005492:Folic Acid / Q000008:administration & dosage; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011732:Pyridoxal Phosphate / Q000097:blood; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D006710:Homocysteine; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6; D005492:Folic Acid