EAL

CKD: Vitamin D (2018)

Author and Year:

Marckmann P et al 2012

PubMed ID:

22822092

Article Title:

Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D.

Authors:

Marckmann P, Agerskov H, Thineshkumar S, Bladbjerg E, Sidelmann J, Jespersen J, Nybo M, Rasmussen L, Hansen D, Scholze A

Journal:

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association

Year of publication:

2012

Volume:

Issue:

Page numbers:

3523-31

Study Design:

Randomized Controlled Trial

Risk of Bias Assessment Rating:

Positive

Inclusion Criteria:

Vitamin D status determined during a CKD outpatient clinic during summer (June-August) Age >18 years Plasma 25OHD <50 nmol/L during above outpatient appointment Informed consent Per clinicaltrials.gov: CKD 3-5 and renal transplant patients

Exclusion Criteria:

Supplementary intake of a total of >10,000 IU ergocalciferol or cholecalciferol within the last 3 months Hypercalcemia (defined in clinicaltrials.gov as Ca . 1,35 mmol/L > 4 weeks despite missing intake of calcium containing preparations and activated vitamin D) Severe hyperphosphatemia (P >2.2 mmol/L at two consecutive measurements > 1 week apart in other Sarcoidosis Malignant disease Psychotic disorder Alcohol or drug abuse Pregnancy Breastfeeding Current participation in other clinical studies Poor understanding of the Danish language Allergy towards soy protein (and peanut protein per clinicaltrials.gov) Fertile women not using safe contraception Estrogen use Meeting any of the exclusion criteria during the intervention period in autumn (Sept-Nov) Acute illness during the 8 week intervention period leading to hospitalization Initiation of dialysis Kidney transplant Death

Research Purpose:

To investigate the impact of vitamin D3 supplementation in CKD patients with hypovitaminosis D including the effects on vitamin D status, parathyroid hormone concentration, fibroblast growth factor (FGF-23), biomarkers of cardiovascular disease, muscle function and subjective health variables.

Blinding efforts:

Stratified by gender and CKD status (conservative management, HD, or transplanted patients) during randomization. Using a computer generated list of random numbers, randomization done by a study manager in the pharmacy at Odense University Hospital in consecutive pairs of two within each of six subgroups. Investigators and participants blinded until study completion. Capsules of both intervention and placebo groups looked identical and were both prepared by the pharmacy at Odense University Hospital. Outcome assessors were not identified.

Study Location:

Denmark

Source(s) of Funding:

Government, Not-for-profit, Industry, Danish Renal Association, Danish Medical Association Research Fun

Please specify names of funders:

Sources of support. The study received financial support from Nyreforeningen (the Danish Renal Association), the Danish Medical Association Research Fund/The Søren Segels and Johanne Wiibroe Segels Research Fund, Helen and Ejnar Bjørnows Research Fund and Genzyme Corporation (P.M.).

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?		???
	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?	???
	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?	Yes
	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?		???
	7.1.	Were primary and secondary endpoints described and relevant to the question?	No
	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?	???
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	???
	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)?	No
	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