Abstract
End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013–March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, ∆LF:HF: 0.20 ± 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: ∆LF:HF: 0.15 ± 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. Trial Registration: ClinicalTrials.gov, NCT01774812.
Highlights
Patients with end-stage kidney disease (ESKD) have 10–100 times greater risk of cardiovascular death compared to the general population, with sudden arrhythmic cardiac death (SCD) accounting for approximately 25% of all cardiovascular-related deaths [1]
Suppressed heart rate variability (HRV), a measure of cardiac autonomic nervous system activity commonly depressed in ESKD patients [3], has been shown to predict SCD risk [4,5] and suggests that treatments aimed at normalizing HRV may translate into improved cardiac outcomes
We have previously shown that vitamin D3 supplementation is associated with normalization of HRV in healthy humans [18] and increased cardioprotective vagal activity in patients with Immunoglobluin A (IgA) nephropathy [19], suggesting that low vitamin D levels may mediate increased risk via the cardiac autonomic nervous system, though this has not been examined in a randomized-controlled trial
Summary
Patients with end-stage kidney disease (ESKD) have 10–100 times greater risk of cardiovascular death compared to the general population, with sudden arrhythmic cardiac death (SCD) accounting for approximately 25% of all cardiovascular-related deaths [1]. To date, no randomized trials have shown increased survival with vitamin D supplementation [15,16,17] in ESKD, treatment with the activated vitamin D analogue paricalcitol decreased cardiovascular-related hospitalizations compared to those treated with placebo [16,17]. We have previously shown that vitamin D3 supplementation is associated with normalization of HRV in healthy humans [18] and increased cardioprotective vagal activity in patients with Immunoglobluin A (IgA) nephropathy [19], suggesting that low vitamin D levels may mediate increased risk via the cardiac autonomic nervous system, though this has not been examined in a randomized-controlled trial
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