Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study.
Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29. 9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5, 10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C --> T and 1298A --> C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.
Sunder-Plassmann
Gere
G
Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Vienna, Austria.
Födinger
Manuela
M
Klinisches Institut für Medizinische und Chemische Labordiagnostik, University of Vienna, Vienna, Austria.
Buchmayer
Heidi
H
Klinisches Institut für Medizinische und Chemische Labordiagnostik, University of Vienna, Vienna, Austria.
Papagiannopoulos
Menelaos
M
Klinisches Institut für Medizinische und Chemische Labordiagnostik, University of Vienna, Vienna, Austria.
Wojcik
Jadwiga
J
Klinisches Institut für Medizinische und Chemische Labordiagnostik, University of Vienna, Vienna, Austria.
Kletzmayr
Josef
J
Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Vienna, Austria.
Enzenberger
Brigitte
B
3. Medizinische Abteilung, Krankenhaus Lainz, Vienna, Austria.
Janata
Oskar
O
1. Medizinische Abteilung, Donauspital, Vienna, Austria.
Winkelmayer
Wolfgang C
WC
1. Medizinische Abteilung, Kaiser Franz Josef Spital, Vienna, Austria.
Paul
Gernot
G
1. Medizinische Abteilung, Donauspital, Vienna, Austria.
Auinger
Martin
M
3. Medizinische Abteilung, Krankenhaus Lainz, Vienna, Austria.
Barnas
Ursula
U
1. Medizinische Abteilung, Donauspital, Vienna, Austria.
Hörl
Walter H
WH
Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Vienna, Austria.
D000704:Analysis of Variance; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D016896:Treatment Outcome
D006397:Hematinics; D005492:Folic Acid