EAL

CKD: Folate (2018)

Author and Year:

Bostom A et al 2011

PubMed ID:

Article Title:

Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.

Authors:

Bostom A, Carpenter M, Kusek J, Levey A, Hunsicker L, Pfeffer M, Selhub J, Jacques P, Cole E, Gravens-Mueller L, House A, Kew C, McKenney J, Pacheco-Silva A, Pesavento T, Pirsch J, Smith S, Solomon S, Weir M

Journal:

Circulation

Year of publication:

2011

Volume:

123

Issue:

Page numbers:

1763-70

Study Design:

Randomized Controlled Trial

Risk of Bias Assessment Rating:

Positive

Inclusion Criteria:

Transplant 6 months or more post–kidney transplant Ccr rate z30 mL/min for men or z25 mL/min for women (unisex cut point z30 mL/min beforeJuly 2005) tHcy z12.0 Amol/L for men or z11.0 Amol/L forwomen Informed consent Cognitive function adequate for patient to give accurate information Adequate transportation facilities Geographically accessibility for follow-up within 120 days of screening Age 35 to 75 y at time of randomization

Exclusion Criteria:

Presence of cancer, end-stage congestive heart failure, liver, or pulmonary disease, progressive human immunodeficiency virus or other chronic wasting illness, which in the opinion of the study physician would limit the life expectancy of the patient to less than 2 years or prevent evaluation of recurrent or de novo CVD, other conditions that prevent reliable participation in the study, such as refractory depression, severe cognitive impairment, or alcoholism or other substance abuse, history of solid organ transplant other than the kidney or pancreas. Pregnant or lactating women or women of childbearing potential not practicing birth control Less than 3 m post–acute myocardial infarction or stroke, or less than 3 months post–coronary artery, renal artery, or lower extremity artery percutaneous transluminal coronary angioplasty, or lower extremity amputation; less than 6 m post–coronary artery bypass graft surgery, abdominal aortic aneurysm; participation in another clinical tria

Research Purpose:

To determine whether decreasing tHcy levels with a multivitamin containing high doses of folic acid, vitamin B6, and vitamin B12 would reduce their risk of CVD outcomes compared to treatment with a “low-dose” multivitamin devoid of folic acid and with estimated average requirement amounts of vitamins B6 and B12.

Blinding efforts:

Double-Blinded

Study Location:

multi-center; USA

Source(s) of Funding:

Government

Please specify names of funders:

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Office of Dietary Supplements, NIH

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		No
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes