Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients

• Published in: American journal of kidney diseases Vol. 37; no. 4; pp. 758 - 765
• Main Authors: Hauser, Anna-Christine, Hagen, Wolfgang, Rehak, Peter H., Buchmayer, Heidi, Födinger, Manuela, Papagiannopoulos, Menelaos, Bieglmayer, Christian, Aspner, Robert, Köller, Elke, Ignatescu, Mihaela, Hörl, Walter H., Sunder-Plassmann, Gere
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Orlando, FL Elsevier Inc 01-04-2001; Elsevier
• Subjects: Biological and medical sciences; Double-Blind Method; Drug Administration Schedule; Drug toxicity and drugs side effects treatment; Erythrocytes - chemistry; Female; Folic Acid - administration & dosage; Folic Acid - blood; Folic Acid - therapeutic use; Genotype; Homocysteine - blood; Humans; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - drug therapy; Infusions, Intravenous; Leucovorin - administration & dosage; Leucovorin - therapeutic use; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors - blood; Oxidoreductases Acting on CH-NH Group Donors - genetics; Pharmacology. Drug treatments; Pyridoxine - blood; Renal Dialysis; Toxicity: nervous system and muscle; Treatment Outcome; Vitamin B 12 - blood; folate; folinic acid; hemodialysis (HD); Total homocysteine (tHcy); vitamin B6; vitamin B12; methylenetetrahydrofolate reductase (MTHFR); folic acid; Human; Nervous system diseases; Thiol; Intravenous administration; Hemodialysis; Treatment efficiency; Metabolic diseases; Enzymopathy; Folic acid; Cerebral disorder; Genetic disease; Blood plasma; Sulfur containing aminoacid; Extrarenal dialysis; Chemotherapy; Randomization; Controlled environment study; Central nervous system disease; Double blind study; Complication; Comparative study; Aminoacid disorder; Quantitative analysis
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1016/S0272-6386(01)80125-6

The effectiveness of intravenous folinic acid or intravenous folic acid for the treatmentof hyperhomocysteinemia of hemodialysis patients is unknown. In a randomized, controlled, double-blind trial, 66 hemodialysis patients were administered either 15 mg of folic acid or an equimolar amount (16.1 mg) of folinic acid intravenously three times weekly. Normalization of total homocysteine (tHcy) plasma levels after 4 weeks of treatment was achieved in 10 patients (30.3%) in the folic-acid group and 6 patients (18.2%; P = 0.389) in the folinic-acid group (normalization at any time during the study period in 39.4% and 33.3% of the patients; P = 0.798). The relative reduction in tHcy plasma levels at week 4 was 32.2% in the folic-acid group and 34.1% in the folinic-acid group. A high baseline tHcy plasma concentration (P = 0.00001), methylenetetrahydrofolate reductase (MTHFR) 677TT/1298AA genotype (P = 0.03540), and low red blood cell folate concentrations (P = 0.2285) were associated with a better relative response to treatment. Normalization of tHcy plasma levels was dependent on a lower baseline tHcy level (P = 0.01976), younger age (P = 0.00896), and MTHFR 677TT/1298AA or 677CT/1298AC genotypes (P = 0.00208 and P = 0.02320, respectively). A 4-week course of intravenous folinic acid is not superior to intravenous folic acid in reducing elevated tHcy plasma levels in hemodialysis patients. The response to treatment is predicted by tHcy plasma level, red blood cell folate content, and MTHFR genotype.