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

Abstract

SummaryBackground and objectives Observational studies suggest that calciferol supplementation may improve laboratory and patient-level outcomes of hemodialysis patients with reduced 25-hydroxyvitamin D [25(OH)D] levels. This randomized controlled trial examined effects of cholecalciferol supplementation in patients on hemodialysis.Design, setting, participants, & measurements Sixty patients with 25(OH)D levels #24 ng/ml (#60 nmol/L) were randomized to receive 50,000 IU oral cholecalciferol or placebo, once weekly for 8 weeks and then monthly for 4 months. At baseline (autumn 2011) and 6 months, testing evaluated muscle strength, functional capacity, laboratory parameters, pulse wave velocity (PWV), and health-related quality of life (HRQOL) using the Kidney Disease Quality of Life-36 survey.Results Patients were well matched by treatment allocation. Median age was 62 years (range, 20-86), 52% were women, 55% had a history of diabetes, and mean serum 25(OH)D was 1765 ng/ml (43613 nmol/L). Patients were assessed over 6 months by repeated-measures ANOVA. Patients allocated to cholecalciferol had significantly higher values of 25(OH)D (P,0.001), 1,25-dihydroxyvitamin D (P=0.04), and tartrate-resistant acid phosphatase-5b) (P=0.04) and a greater reduction in phosphorus values (P=0.03) than placebo-treated patients Values of serum calcium, intact parathyroid hormone, and episodes of hypercalcemia and hyperphosphatemia did not differ significantly between the groups. No significant differences were detected in muscle strength, functional capacity, PWV, or HRQOL.Conclusions In this randomized controlled trial, patients supplemented with cholecalciferol had higher 25(OH)D, 1,25-dihydroxyvitamin D, and tartrate-resistant acid phosphatase-5b levels, without increased calcium or phosphorus values. However, no effects were detected in muscle strength, functional capacity, PWV, or HRQOL.

Nutritional Vitamin D Supplementation in Dialysis

“…A trial of 38 HD patients found no effect on PTH, monocytes, T-cell differentiation, or cytokine production (31). A recent study by Hewitt et al (n=60) similarly found no effects of cholecalciferol supplementation on muscle strength, functional capacity, pulse wave velocity, or health-related quality of life (32).…”

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

“…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.…”

Mushroom Clouds for Vitamin D?

“…The study reports no significant differences between groups in the primary end point of epoetin requirements or in BP, change in serum PTH, phosphorus, calcium, inflammatory markers, or use of cinacalcet, calcitriol, or phosphate binders. 9 These data 9 and those of a similar but smaller randomized, controlled trial using cholecalciferol 11 erode support for the use of nutritional vitamin D in the short-term management of anemia for patients on dialysis or patient-level outcomes assessed by functional or muscle strength testing, BP control, differences in lipids, insulin resistance, inflammatory markers, vascular compliance as measured by pulse wave velocity, or quality of life. Although vitamin D is relatively inexpensive and adverse effects are infrequent, the additional pill burden and lack of proven efficacy suggest that, for patients with vitamin D values in the described range, relatively short-term treatment for those indications is unjustified.…”

“…For patients with CKD stages 2-4, treatment with cholecalciferol reduces PTH levels and may impede PTH values from rising. 12,13 Cholecalciferol treatment is also reported to maintain or increase calcitriol levels, 12,14 even for patients on dialysis, 11 although the clinical benefit of this is unknown. Heavy proteinuria can result in substantial losses of vitamin D binding protein (DBP) and may contribute to vitamin D deficiency, whereas treatment with vitamin D may ameliorate podocyte injury and reduce proteinuria.…”

“…Doses of 50,000 IU cholecalciferol or ergocalciferol, initially weekly and then, monthly achieve 25OHD levels $20 ng/ml (50 nmol/L) in most patients on dialysis. 9,11 However, megadose treatments should be avoided; a randomized, controlled trial of 2256 elderly community-dwelling women reported that a single annual cholecalciferol dose of 500,000 IU led to increased falls and fractures, 17 possibly by inhibiting bone mineralization, leading to osteomalacia, and affecting muscle strength. Lower-dose vitamin D that corresponds to the Institute of Medicine recommended daily allowance of 600 IU and is well below the suggested adult tolerable upper limit of 4000 IU daily, 18 also seems effective in raising 25OHD levels and reducing levels of serum PTH values in earlier stages of CKD.…”