Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease--results of the renal Hope-2 study.

Abstract

BACKGROUND:

Elevated plasma homocysteine levels are reported to be associated with higher rates of vascular diseases. Plasma homocysteine increases in chronic kidney disease (CKD) and could contribute to the increased cardiovascular risk in CKD.

METHODS:

Participants aged 55 years or older with CKD, defined as estimated GFR<60 ml/min and at high cardiovascular risk, were randomly assigned to the combination of folic acid, 2.5 mg, vitamin B6, 50 mg and vitamin B12, 1 mg (n = 307) or placebo (n = 312) daily for 5 years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction and stroke.

RESULTS:

Mean baseline plasma homocysteine was 15.9 +/- 7.3 micromol/l in the active treatment group and 15.7 +/- 5.7 micromol/l in placebo group and decreased to 11.9 +/- 3.3 micromol/l (P < 0.001) on active treatment (15.5 +/- 4.5 on placebo). Primary outcome events occurred in 90 participants (29.3%) on active therapy and in 80 (25.6%) on placebo (relative risk, 1.19; 95% confidence interval, 0.88-1.61; P = 0.25). There were no significant treatment benefits on death from cardiovascular causes (1.24; 0.84-1.83), myocardial infarction (1.10; 0.76-1.61) and stroke (1.00; 0.54-1.85). More participants in the active treatment group were hospitalized for heart failure (1.98; 1.21-3.26; P = 0.007) and for unstable angina (1.70; 1.02-2.83; P = 0.04). Incidence of primary outcome increased with decreasing GFR.

CONCLUSIONS:

Active treatment with B vitamins lowered homocysteine levels in participants with CKD but did not reduce cardiovascular risk.

• Authors: Johannes F E Mann, Patrick Sheridan, Matthew J McQueen, Claes Held, J Malcolm O Arnold, George Fodor, Salim Yusuf, Eva M Lonn, HOPE-2 investigators
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 23 Issue 2 Pg. 645-53 (Feb 2008) ISSN: 1460-2385 [Electronic] England
• PMID: 18003666 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Homocysteine
• Vitamin B 6
• Folic Acid
• Vitamin B 12

Topics

• Aged
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Folic Acid (therapeutic use)
• Homocysteine (blood)
• Humans
• Kidney Failure, Chronic (blood)
• Male
• Vitamin B 12 (therapeutic use)
• Vitamin B 6 (therapeutic use)