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Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

ABSTRACT: Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD.We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.73 m2. Change in pulse wave velocity (PWV) was measured after 6 months of treatment with a fixed dose of oral calcifediol (5000 IU 25-hydroxyvitamin D3), calcitriol (0.5 µg 1,25-dihydroxyvitamin D3), or placebo, thrice weekly.Eighty-seven participants were evaluated. Mean age was 66 years, 71% were men, 40% were diabetic, and mean baseline PWV was 11.5 m/s (SD=3.9 m/s). After 6 months, the PWV decreased in the calcifediol group (mean change, -1.1; 95% confidence interval [95% CI], -2.2 to 0.1 m/s), remained unchanged in the calcitriol group (mean change, 0.2; 95% CI, -0.9 to 1.4 m/s), and increased in the placebo group (mean change, 1.1; 95% CI, -0.1 to 2.2 m/s). The overall P value for between-arm changes was 0.03. Absolute PWV change was significantly different between groups (P=0.04): the combined vitamin D treatment group saw decreased PWV (mean change, -0.4; 95% CI, -1.2 to 0.4 m/s) whereas the placebo group saw increased PWV (mean change, +1.1; 95% CI, -0.1 to 2.2 m/s). The treatment group demonstrated significantly decreased serum parathyroid hormone (mean difference, -0.5; 95% CI, -0.7 to -0.3 ln[pg/ml]; P<0.001) and increased calcium (mean difference, 0.4; 95% CI, -0.1 to 0.7 mg/dl; P=0.02). In observational analysis, participants in the highest 25-hydroxyvitamin D tertile at trial end had significant decreases in PWV (mean change, -1.0; 95% CI, -2.0 to 0.0 m/s) compared with the middle and lowest tertiles (P<0.01). Side effects were minor and rare.Six months of supplemental vitamin D analogs at fixed doses may achieve a reduction of PWV in patients with advanced CKD. Because the treatment effect was attenuated when baseline PWV was included as a covariate, these findings should be replicated in larger populations and further studied.

SUBMITTER: Levin A

PROVIDER: S-EPMC5586581 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

Levin Adeera A Tang Mila M Perry Taylor T Zalunardo Nadia N Beaulieu Monica M Dubland Joshua A JA Zerr Kelly K Djurdjev Ognjenka O

Clinical journal of the American Society of Nephrology : CJASN 20170526 9

<h4>Background and objectives</h4>Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD.<h4>Design, setting, participants, & measurements</h4>We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to ...[more]

PMID: 28550081

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Project description:BackgroundVascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown.MethodsTo determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study.ResultsWe included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures.ConclusionsVitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD.Clinical trial registry name and registration numberVitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).

Project description:BackgroundObese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health.ObjectivesThe aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects.MethodsWe conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome.ResultsDose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group.ConclusionsCorrection of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

Project description:BackgroundVitamin D deficiency is associated with cardiovascular (CV) risk in multiple populations, including those with chronic kidney disease (CKD). The active form of the hormone (1,25 OH2D3) binds to receptors in multiple organs. CKD patients are deficient in both 25 Vitamin D and 1,25 OH2D3. Clinical trial data demonstrating the benefits of vitamin D formulations are limited, and fail to show significant benefits on CV outcomes, and have compared different compounds, in various populations, and focused on a variety of outcomes. A understanding of the mechanism by which different vitamin D compounds confer CV protection in CKD is important for the design of future studies.Methods/designThis 3 arm randomized prospective double-blinded placebo-controlled study examining the impact of calcitriol (1,25 OH2D3) and 25-hydroxyvitamin D3 supplementation compared to placebo on vascular stiffness, as measured by pulse wave velocity (PWV). Patients are enrolled from 2 tertiary care institutions if they meet inclusion criteria (stable estimated glomerular filtration rate (eGFR) between 15-45ml/min, <±5ml/min change in previous 6 months), on stable doses of renin-angiotensin aldosterone system blockade. For those already receiving vitamin D therapies, a 3 month washout period before randomization is mandatory. Treatment duration is 6 months; medications are given thrice weekly in fixed doses. The primary outcome measure is Vascular stiffness, measured non-invasively by pulse wave velocity (PWV). Other measurements include BP, kidney function and serial blood levels of biomarkers. The primary analysis will compare any vitamin D therapy versus placebo for the primary outcome defined as the change of PWV from baseline to 6 months. Analysis of covariance will be used to detect differences between vitamin D preparations in the magnitude of reduction in PWV.DiscussionThis study is novel in that we are using a robust study design in CKD patients (not on dialysis) comparing placebo to different forms of vitamin D supplementation in fixed doses, irrespective of baseline values. We hope to demonstrate the biological mechanistic effect of vitamin D supplementation on vascular function in order for this information to be used in designing larger randomized controlled trials.Trial registrationCurrent Controlled Trials NCT01247311. Date of Registration: November 12, 2010.

Project description:The role vitamin D intake/production plays in sarcoidosis-associated hypercalcaemia is uncertain. However, authoritative reviews have recommended avoiding sunlight exposure and vitamin D supplements, which might lead to adverse skeletal outcomes from vitamin D insufficiency. We investigated the effects of vitamin D supplementation on surrogate measures of skeletal health in patients with sarcoidosis and vitamin D insufficiency.Randomised, placebo-controlled trial.Clinical research centre.27 normocalcaemic patients with sarcoidosis and 25-hydroxyvitamin D (25OHD) <50 nmol/L.50 000 IU weekly cholecalciferol for 4 weeks, then 50 000 IU monthly for 11 months or placebo.The primary endpoint was the change in serum calcium over 12 months, and secondary endpoints included measurements of calcitropic hormones, bone turnover markers and bone mineral density (BMD).The mean age of participants was 57 years and 70% were women. The mean (SD) screening 25OHD was 35 (12) and 38 (9) nmol/L in the treatment and control groups, respectively. Vitamin D supplementation increased 25OHD to 94 nmol/L after 4 weeks, 84 nmol/L at 6 months and 78 nmol/L at 12 months, while levels remained stable in the control group. 1,25-Dihydroxy vitamin D levels were significantly different between the groups at 4 weeks, but not at 6 or 12 months. There were no between-groups differences in albumin-adjusted serum calcium, 24 h urine calcium, markers of bone turnover, parathyroid hormone or BMD over the trial. One participant developed significant hypercalcaemia after 6 weeks (total cholecalciferol dose 250 000 IU).In patients with sarcoidosis and 25OHD <50 nmol/L, vitamin D supplements did not alter average serum calcium or urine calcium, but had no benefit on surrogate markers of skeletal health and caused one case of significant hypercalcaemia.This trial is registered at the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au). The registration number is ACTRN12607000364471, date of registration 5/7/2007.

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Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

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Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

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