Cardiovascular effects of cholecalciferol treatment in dialysis patients – a randomized controlled trial

Abstract

BackgroundPatients on chronic dialysis are at increased risk of vitamin D deficiency. In observational studies plasma 25-hydroxyvitamin D (p-25(OH) D) levels are inversely correlated with plasma BNP and adverse cardiovascular outcomes. Whether a causal relation exists has yet to be established. The aim of this study was to test the hypothesis that cholecalciferol supplementation improves cardiac function and reduces blood pressure (BP) and pulse wave velocity (PWV) in patients on chronic dialysis.MethodsIn a randomized, placebo-controlled, double-blind study, we investigated the effect of 75 μg (3000 IU) cholecalciferol daily for 6 months, in patients on chronic dialysis. We performed two-dimensional echocardiography, with doppler and tissue-doppler imaging, 24-h ambulatory BP (24-h BP), PWV, augmentation index (AIx), central BP (cBP) and brain natriuretic peptide (BNP) measurements at baseline and after 6 months.ResultsSixty-four patients were allocated to the study. Fifty dialysis patients with a mean age of 68 years (range: 46–88) and baseline p-25(OH) D of 28 (20;53) nmol/l completed the trial. Cholecalciferol increased left ventricular (LV) volume, but had no impact on other parameters regarding LV structure or left atrial structure. LV systolic function, LV diastolic function, PWV, cBP, AIx and BNP were not changed in placebo or cholecalciferol group at follow-up. 24-h BP decreased significantly in placebo group and tended to decrease in cholecalciferol group without any difference between treatments.ConclusionSix months of cholecalciferol treatment in patients on chronic dialysis did not improve 24-h BP, arterial stiffness or cardiac function.Trial registrationNCT01312714, Registration Date: March 9, 2011.

Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial

“…There have been ten previous RCTs with sample size $30 patients and follow-up $8 weeks that have assessed the effects of nutritional vitamin D or calcifediol supplementation in patients on dialysis on iPTH, 19,[22][23][24][25][26][27]31,[33][34][35] and all but one small study 33 is consistent with the present study in finding no effect on iPTH. An absence of effect of nutritional vitamin D on iPTH has also been found in stage IV CKD, 36,37 while at earlier stages of CKD, there appears to be a reduction in iPTH with nutritional vitamin D. The conclusion from a Cochrane evidence review, published in 2009 before many of the above-mentioned trials were completed, concluded that vitamin D is effective in suppressing iPTH, although (not obvious from the abstract) this statement pertains to VDRAs and not to nutritional vitamin D. 38 The results of observational studies lead one to believe that there is a reduction in iPTH in patients on hemodialysis with nutritional vitamin D supplementation, 6,8,18,39 although these studies used historical controls and are limited by other biases inherent with a nonrandomized design.…”

“…43 Potential harms with nutritional vitamin D supplementation include hypercalcemia, hyperphosphatemia, and extraskeletal ossification. In our study, in which 80% or more were concomitantly treated with VDRAs, there were no significant changes in calcium or phosphorus, and this is consistent with all of the other RCTs in patients on hemodialysis, 19,[22][23][24][25][26][27]31,[33][34][35] including one study that administered 200,000 IU of cholecalciferol weekly for 3 weeks. 27 Raising the possibility that there may be harmful outcomes associated with excess nutritional vitamin D administration, an RCT in community dwelling elderly women treated with a one-time dose of 500,000 units of ergocalciferol or placebo found a 15% increase in falls and a 26% increase in fractures in the ergocalciferol arm at 1 year.…”

“…40 We found no change in BP in the present study, consistent with a 6-month trial of cholecalciferol at a dose of 3000 IU daily versus placebo in 64 patients on hemodialysis, which also found no effect on arterial stiffness or cardiac structure or function. 23 Evidence for reduction in CV events with nutritional vitamin D in the general population is lacking. 41 A sequential network meta-analysis of RCTs of nutritional vitamin D supplementation with pooled sample sizes of 48,647 patients from nine trials with myocardial infarction as an outcome and 46,431 patients in eight trials for stroke found no effects of nutritional vitamin D for either outcome and the CIs fell within futility bands, suggesting that any effect of vitamin D would not exceed a 15% relative risk reduction for CV events and a 5% relative risk reduction for mortality.…”

“…Nonrandomized observational studies 6,[18][19][20] and small randomized clinical trials (RCTs) 19,[21][22][23][24][25][26][27] have yielded inconsistent results. Accordingly, there is uncertainty about whether patients on dialysis should be treated with nutritional vitamin D in addition to VDRAs.…”

Evaluation of Responses to Vitamin D3 (Cholecalciferol) in Patients on Dialysis: A Systematic Review and Meta-Analysis

“…Two studies20 22 did not use vitamin D status as a patient selection criterion. Most studies also excluded patients with hypercalcemia and hyperphosphatemia, but one study, Armas et al ,22 did not impose such restrictions.…”