Volume 54, Issue 3 , Pages 440-449, September 2009
Homocysteine Lowering and Cognition in CKD: The Veterans Affairs Homocysteine Study
Background
Individuals with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) have high plasma total homocysteine (tHcy) levels, which may be a risk factor for cognitive impairment. Whether treatment with high-dose B vitamins to decrease high tHcy levels improves cognition in persons with kidney disease is unknown.
Study Design
Randomized controlled trial.
Setting & Participants
A substudy of 659 patients (mean age, 67.3 ± 11.7 years) who participated in a randomized double-blind clinical trial 5 years in duration conducted in 36 US Department of Veterans Affairs medical centers of the effect on all-cause mortality of vitamin-induced lowering of plasma tHcy level. 236 (35.8%) were treated by using dialysis (ESRD) and 423 (64.2%) had a Cockcroft-Gault estimated creatinine clearance of 30 mL/min or less (advanced CKD). All had high tHcy levels (≥15 μmol/L) at baseline. Cognitive assessments began during the follow-up period of the main trial 3 years after treatment began; participants subsequently were retested 1 year later to assess cognitive change.
Intervention
Daily high-dose B vitamin capsule (40 mg of folic acid, 100 mg of vitamin B6, and 2 mg of vitamin B12) or placebo.
Outcomes
Cognitive function at initial assessment and 1 year later.
Measurements
Telephone Interview of Cognitive Status–modified, supplemented with attention, working memory, and executive function tests.
Results
Initial cognitive function was impaired in approximately 19% of patients regardless of treatment assignment (vitamin or placebo) or kidney disease status (advanced CKD or ESRD). Treatment decreased tHcy levels by 26.7%. Unadjusted and adjusted analyses showed that treatment did not improve initial cognitive outcomes or affect subsequent cognitive status 1 year later.
Limitations
Cognitive assessments began after treatment was initiated; cognitive assessment was limited.
Conclusion
Treatment with high daily doses of B vitamins, which decreased tHcy levels, did not affect cognitive outcomes in patients with advanced CKD and ESRD.
Index Words: Cognition, kidney disease, homocysteine, clinical trial
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Originally published online as doi: 10.1053/j.ajkd.2009.05.013 on July 24, 2009.
Because an author of this manuscript is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Michael Shlipak, MD, MPH, University of California, San Francisco) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.
Trial registration: www.clinicaltrials.gov; study number: NCT00032435.
PII: S0272-6386(09)00835-X
doi:10.1053/j.ajkd.2009.05.013
Published by Elsevier Inc.
Volume 54, Issue 3 , Pages 440-449, September 2009
