Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of L-folinic or folic acid.

BACKGROUND We have previously reported that a daily oral high dose of l-folinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients does not provide significantly greater reduction in fasting total homocysteine (tHcy) levels than an equimolar dose of folic acid. The present study uses the affinity/HPLC method to analyze the distribution of plasma folate forms in patients who received l-folinic acid versus those who received folic acid. This was done to investigate claims that renal insufficiency is associated with impaired folate interconversion, a stance that is supportive of the premise that tHcy lowering in these patients is more efficacious with folinic acid and other reduced folates, than folic acid. METHODS Forty-eight chronic and stable hemodialysis patients were block-randomized, based on their screening predialysis tHcy levels, sex, and dialysis center, into two groups treated for 12 weeks with oral folic acid at 15 mg/day or an equimolar amount (20 mg/day) of oral l-folinic acid. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1 mg/day of oral vitamin B12. Folate distribution was determined in plasma of 46 participants (Folinic acid group, N = 22; Folic acid group, N = 24) by using the affinity/HPLC method, with electrochemical (coulometric) detection. RESULTS Both groups had similar baseline geometric means of plasma total folate and similar folate forms distribution. Following treatment, both groups demonstrated similar marked elevation in plasma total folate (geometric mean of the increase: Folinic acid group, +337 ng/mL; Folic acid group, +312 ng/mL; P = 0.796). In the folinic acid-treated group, practically all of the increase in total folate was due to 5-methyltetrahydrofolate. In the folic acid-treated group 5-methyltetrahydrofolate accounted for 35% of the increase in total folate and the remainder was unmethylated folic acid. CONCLUSIONS Data from the present findings suggest that defects in folate absorption or impairment in folate interconversion are not the cause of the persistent hyperhomocysteinemia in hemodialysis patients.

[1]  C. Stehouwer,et al.  Homocysteine-lowering treatment: an overview , 2001, Expert opinion on pharmacotherapy.

[2]  R. Tremblay,et al.  Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins. , 2000, Kidney international.

[3]  Z. Massy,et al.  Controlled comparison of L-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients. , 2000, Circulation.

[4]  J. Selhub,et al.  Analysis of folate form distribution by affinity followed by reversed- phase chromatography with electrical detection. , 2000, Clinical chemistry.

[5]  Z. Massy.  Reversal of hyperhomocyst(e)inaemia in chronic renal failure-is folic or folinic acid the answer? , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[6]  Z. Massy,et al.  Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. , 1999, Kidney international.

[7]  B. Culleton,et al.  Hyperhomocysteinemia in chronic renal disease. , 1999, Journal of the American Society of Nephrology : JASN.

[8]  J. Brosnan,et al.  Net uptake of plasma homocysteine by the rat kidney in vivo. , 1995, Atherosclerosis.

[9]  E. Livant,et al.  Plasma folate conjugase activities and folate concentrations in patients receiving hemodialysis , 1994 .

[10]  J. C. Schmitz,et al.  Disposition of folic acid and its metabolites: A comparison with leucovorin , 1994, Clinical pharmacology and therapeutics.

[11]  A. Heyns,et al.  Aspects of Folate Metabolism in Renal Failure , 1977, British journal of haematology.

[12]  I. Goldman,et al.  Inhibition of the membrane transport of folates by anions retained in uremia. , 1975, The Journal of laboratory and clinical medicine.

[13]  P. Jacques,et al.  L-folinic acid versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients , 2001 .

[14]  I. Rosenberg,et al.  High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients. , 1996, Kidney international.

[15]  J. Selhub,et al.  The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. , 1992, The American journal of clinical nutrition.

[16]  N. Vaziri,et al.  Intestinal absorption of 5-methyltetrahydrofolate in experimental uremia. , 1984, Acta vitaminologica et enzymologica.