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


BACKGROUND
ClinicalTrials.gov, NCT01774812.
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. mcmann@ucalgary.ca.|Libin Cardiovascular Institute of Alberta, Calgary, AB T2N 4Z6, Canada. mcmann@ucalgary.ca.
Michelle C
MC
Mann
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. exner@ucalgary.ca.|Libin Cardiovascular Institute of Alberta, Calgary, AB T2N 4Z6, Canada. exner@ucalgary.ca.
Derek V
DV
Exner
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. brenda.hemmelgarn@albertahealthservices.ca.|Libin Cardiovascular Institute of Alberta, Calgary, AB T2N 4Z6, Canada. brenda.hemmelgarn@albertahealthservices.ca.|Department of Community Health Sciences, University of Calgary, Calgary, AB T2N 4Z6, Canada. brenda.hemmelgarn@albertahealthservices.ca.
Brenda R
BR
Hemmelgarn
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. dahanley@ucalgary.ca.|Osteoporosis and Metabolic Bone Disease Centre, Calgary, AB T2T 5C7, Canada. dahanley@ucalgary.ca.
David A
DA
Hanley
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. turin.chowdhury@albertahealthservices.ca.
Tanvir C
TC
Turin
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. jennifer.macrae@albertahealthservices.ca.|Libin Cardiovascular Institute of Alberta, Calgary, AB T2N 4Z6, Canada. jennifer.macrae@albertahealthservices.ca.
Jennifer M
JM
MacRae
Department of Medicine, University College London, London NW3 2PF, UK. d.wheeler@ucl.ac.uk.
David C
DC
Wheeler
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. dsola@ucalgary.ca.
Darlene Y
DY
Sola
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. sramesh@ucalgary.ca.|Libin Cardiovascular Institute of Alberta, Calgary, AB T2N 4Z6, Canada. sramesh@ucalgary.ca.
Sharanya
S
Ramesh
Department of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada. Sofia.Ahmed@albertahealthservices.ca.|Libin Cardiovascular Institute of Alberta, Calgary, AB T2N 4Z6, Canada. Sofia.Ahmed@albertahealthservices.ca.
Sofia B
SB
Ahmed
autonomic nervous system; chronic kidney disease; heart rate variability; hemodialysis; vitamin D
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