Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D

Nephrology Dialysis Transplantation (2012), First published online: July 20, 2012
Peter Marckmann 1,2?, Hanne Agerskov 1, Sasikala Thineshkumar 1,2, Else-Marie Bladbjerg 3, Johannes J. Sidelmann 3, Jørgen Jespersen 3, Mads Nybo 4, Lars M. Rasmussen 4, Ditte Hansen 5 and Alexandra Scholze 1,2
1 Clinical Research Unit, Department of Nephrology, Odense University Hospital, Odense, Denmark
2 Clinical Institute, University of Southern Denmark, Odense, Denmark
3 Unit for Thrombosis Research, Institute of Public Health, University of Southern Denmark and Department of Clinical Biochemistry, Hospital of Southwest Denmark, Esbjerg, Denmark
4 Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark
5 Department of Internal Medicine, Roskilde Hospital, Roskilde, Denmark
Correspondence to: Peter Marckmann; E-mail: peter.marckmann at dadlnet.dk
Received December 2, 2011. Accepted March 19, 2012.

Background Hypovitaminosis D is common in chronic kidney disease (CKD).
Effects of 25-hydroxyvitamin D replenishment in CKD are not well described.

Methods An 8-week randomized, placebo-controlled, double-blind parallel intervention study was conducted in haemodialysis (HD) and non-HD CKD patients. Treatment consisted of 40 000 IU of cholecalciferol orally per week. Plasma 25-hydroxyvitamin D (25-OHD), plasma 1,25-dihydroxyvitamin D (1,25-diOHD), plasma parathyroid hormone (PTH), serum phosphate, ionized serum calcium and serum fibroblast growth factor 23 (FGF-23) were analysed. We also investigated biomarkers related to cardiovascular disease (plasma D-dimer, plasma fibrinogen, plasma von Willebrand factor antigen and activity, plasma interleukin 6, plasma C-reactive protein, blood pressure, aortic augmentation index, aortic pulse wave velocity and 24-h urinary protein loss). Objective and subjective health variables were assessed (muscle function tests, visual analogue scores and Health Assessment Questionnaire).

Results Fifty-two CKD patients with 25-OHD <50 nmol/L at screening were included. Cholecalciferol supplementation led to a significant increase to a median of 155 nmol/L 25-OHD (interquartile range 137–173 nmol/L) in treated patients (n = 25, P < 0.001).

In non-HD patients, we saw a significant increase in 1,25-diOHD (n = 13, P < 0.01) and a lowering of PTH (n = 13, P < 0.001).

This was not observed in HD patients. Cholecalciferol supplementation caused a significant increase in serum calcium and FGF-23.

Conclusions 25-OHD replenishment was effectively obtained with the employed cholecalciferol dosing. In non-HD patients, it had favourable effects on 1,25-diOHD and PTH. Vitamin D-supplemented patients must be monitored for hypercalcaemia.

The present study could not identify significant pleiotropic effects of 25-OHD replenishment.

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Summary by author for Vitamin D Life

• 40,000 IU cholecalciferol weekly for just 8 weeks to 25 patients with Chronic Kidney Disease and hypovitaminosis D (vitamin D levels below 20 nanograms/mL) , placebo to 24 matched controls
• Active treatment corrected hypovitaminosis in all patients with final average vitamin D levels of 62 nanograms/mL versus 9 nanograms/mL in the placebo group.
  Note: Vitamin D levels would probably have been much higher if the trial had lasted longer
  Vitamin D half-life is 4-8 weeks.
• Beneficial effects on bone metabolism were seen in the subgroup of patients who were NOT undergoing dialysis, but not in patients undergoing dialysis

See also Vitamin D Life

• Overview Kidney and Vitamin D
• Kidney Conference had many Vitamin D papers – May 2012
• Need at least 80 ng of vitamin D if have chronic kidney disease – May 2012
• Adding Vitamin decreased kidney deaths by 4x – Dec 2010
  It is amazing that such excellent results were buried in the paper. They were not in the title nor abstract.
  This is the result of about 10 trials with about 5,000 kidney disease patients.
  Note: some of the trials were terminated as they felt it was morally wrong to not give vitamin D to all of the Kidney patients
• All items in Kidney and Vitamin D 193 items
• Chronic Kidney Disease reduced with 3500 IU average vitamin D – RCT Aug 2012
• How often should I take 50000 IU of vitamin D