CKD: Folate (2018)

Author and Year:
Xu X et al 2016
PubMed ID:
Article Title:
Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial.
Xu X, Qin X, Li Y, Sun D, Wang J, Liang M, Wang B, Huo Y, Hou F
JAMA Internal Medicine
Year of publication:
Page numbers:
Study Design:
Randomized Controlled Trial
Risk of Bias Assessment Rating:
Inclusion Criteria:
Participant in the China Stroke Primary Prevention Study. Inclusion criteria for the main study includes: BP>=140/90 in two screening visits or receiving anti-hypertension treatment, known MTHFR C677T genotype, pre-menopausal women agreed to use contraceptives during the trial (per Age 45-75 years Resident of a community within the Jiangsu province (15,486 were randomized) Informed consent for the renal sub-study was waived
Exclusion Criteria:
Per for main study: history of stroke, myocardial infarction, physician diagnosed heart failure; post coronary revascularization; severe somatic disease such as cancer; secondary hypertension; congenital or acquired organic heart disease; contraindicated to ACE-inhibitor; history of ACEI adverse events; current long term use of folic acid, vitamin B12, or vitamin B6; pregnant or breastfeeding woman; severe mental disorders; lab tests indicating abnormal liver or kidney function; unwilling to participate in the trial or unwilling to change current anti-hypertensive treatment For the renal sub-study: Missing eGFR at baseline or eGFR <30 mL/min/1.73m2 Participants with unknown renal outcomes were excluded from the renal outcomes analysis (N=2187, 14%) Participants who were alive at the exit visit with unknown renal outcomes were excluded from the composite outcome analysis (N=1802, 12%)
Research Purpose:
This report, a pre-specified renal sub-study of the China Stroke Primary Prevention Trial (CSPPT), sought to examine the effects of combination of enalapril and folic acid with enalapril alone in reducing the risk of renal function decline in a hypertensive population.
Blinding efforts:
Method of randomization not described in paper but the online protocol reported participants were randomized in a fixed block size of four and stratified on MTHFR C677T genotype in a 1:1 ratio. Per, subject, caregiver, investigator and outcomes assessor were blinded. Per online protocol tablets were encapsulated for blinding purposes.
Study Location:
Source(s) of Funding:
Please specify names of funders:
Major State Basic Research Development Program of China National Key Technology Support Program of China Major Scientific and Technological Planning Project of Guangzhou Science, Technology and Innovation Committee of Shenzhen National Natural Science Foundation of China Special Project on the Integration of Industry, Education and Research of Guangdong Province Guangzhou Clinical Research Center for Chronic Kidney Disease Program
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? Yes
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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
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? Yes
  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? Yes
  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