25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Hemodialysis

Abstract

Summary Background and objectives Recent understanding of extrarenal production of calcitriol has led to the exploration of native vitamin D treatment in dialysis patients. This paper reports the pharmacokinetics of 25-hydroxyvitamin D response to 10,333 IU cholecalciferol given weekly in subjects on chronic dialysis. Design, setting, participants, & measurements This randomized, double-blind, placebo-controlled trial of 15 weeks of oral cholecalciferol in subjects with stage 5 CKD requiring maintenance hemodialysis was conducted from November of 2007 to March of 2010. The time course of serum 25-hydroxyvitamin D was measured over the course of treatment. Additionally, blood was drawn at baseline and last visit for calcium, phosphorus, calcitriol, and parathyroid hormone levels. Results The median (interquartile range) baseline 25-hydroxyvitamin D level was 13.3 (11.1–16.2) ng/ml for the treatment group and 15.2 (10.7–19.9) ng/ml for the placebo group. 25-hydroxyvitamin D steady state levels rose by 23.6 (19.2–29.9) ng/ml in the treatment group, and there was no change in the placebo group. Calcitriol levels also increased significantly in the treatment group. There were no significant changes in levels of calcium, albumin, phosphorus, and parathyroid hormone in either group. Conclusions Cholecalciferol (10,333 IU) given weekly in patients on chronic hemodialysis produces a steady state in 25-hydroxyvitamin D of approximately 24 ng/ml.

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

“…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.…”

“…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.…”

“…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.…”

Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis Patients

“…In the subgroup of cholecalciferol-treated patients for whom interim 25(OH)D levels were available, maximal levels were achieved by 8-12 weeks from commencement of therapy. This is consistent with another CKD-5D study, in which mean 25(OH)D levels of 30 ng/ml (75 nmol/L) were attained between 40 and 60 days from initiation of therapy (22). However, compared with this study, those patients had lower baseline 25(OH)D levels and were treated with lower cholecalciferol doses.…”

“…A similar relationship of 25(OH) D to 1,25(OH) 2 D levels has been reported in anephric patients (23) and in a recent RCT of patients on dialysis (22). Whereas the former article supports the concept of extrarenal conversion of 25(OH)D to 1,25(OH) 2 D, the latter study and current trial cannot exclude the possibility of preserved or less inhibited 1-a-hydroxylase activity in vitamin D-supplemented patients.…”