The VITAH Trial-Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial

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.

Keywords: autonomic nervous system; chronic kidney disease; heart rate variability; hemodialysis; vitamin D.

Conflict of interest statement

Derek Exner is the Canada Research Chair in Cardiovascular Clinical Trials and receives unrestricted support from GE Healthcare. S.B. Ahmed is supported by Alberta Innovates—Health Solutions. Brenda Hemmelgarn, Jennifer MacRae, and Sofia Ahmed are supported by a joint initiative between Alberta Health and Wellness and the Universities of Alberta and Calgary. The authors declare that funding sources had no role in the design, conduct, or reporting of this study. None of the authors have any conflicts of interests directly relevant to this study to declare.

Figures

Figure A1

Overview of the VITAH Trial.

Figure A2

Parathyroid hormone response to vitamin D supplementation.

Figure 1

Consolidated Standard of Reporting Trials (CONSORT) diagram for trial recruitment and participation.

Figure 2

Low frequency to high frequency ratio (LF:HF) responses to vitamin D supplementation.

Figure 3

LF:HF responses to vitamin D supplementation, stratified by achieved vitamin D status; (A) responses to alfacalcidol alone; (B) responses to alfacalcidol and ergocalciferol combined supplementation.

Figure 3

LF:HF responses to vitamin D supplementation, stratified by achieved vitamin D status; (A) responses to alfacalcidol alone; (B) responses to alfacalcidol and ergocalciferol combined supplementation.