Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study

Delanaye, Pierre; Weekers, Laurent; Warling, Xavier; Moonen, Martial; Smelten, Nicole; Médart, Laurent; Krzesinski, Jean-Marie; Cavalier, Étienne

doi:10.1093/ndt/gft001

Cited by 72 publications

(67 citation statements)

References 40 publications

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“…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.…”

Section: Discussionsupporting

confidence: 88%

“…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.…”

Section: Discussionsupporting

confidence: 82%

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

Miskulin

Majchrzak²,

Tighiouart

et al. 2015

JASN

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Locally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D ,30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean6SD serum 25(OH)D increased from 16.065.9 ng/ml at baseline to 39.2614.9 ng/ml in the ergocalciferol arm and did not change (16.966.4 ng/ml and 17.567.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 82%

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

Miskulin

Majchrzak²,

Tighiouart

et al. 2015

JASN

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“…Our patients who were compliant with prescribed ergocalciferol did not have hypercalcemia at a disproportionate rate compared to non-compliant patients, suggesting concordance with the findings of a randomized controlled trial of cholecalciferol supplementation that 25(OH)D supplementation is safe in this population [21]. The reason for the lack of an observed calcemic effect are suggested by a study by Armas et al [22] that found that raising serum 25(OH)D to normal levels in HD patients using weekly cholecalciferol supplementation had no effect on intestinal absorption of calcium measured using a standardized labeled calcium meal.…”

Section: Discussionsupporting

confidence: 85%

Prevalence of 25-OH Vitamin D Deficiency in a Population of Hemodialysis Patients and Efficacy of an Oral Ergocalciferol Supplementation Regimen

Porter¹,

Gilmartin

Srisakul

et al. 2013

Am J Nephrol

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Background/Aims: Optimal dosing regimens for 25-OH vitamin D (VitD) deficiency are unknown in hemodialysis (HD) patients. Our aim was to evaluate the efficacy of prescribing ergocalciferol supplementation based on KDOQI guidelines for chronic kidney disease (CKD) stages III-IV in HD patients. Methods: We conducted a retrospective study of 96 urban, predominately African-American HD patients at a single-center dialysis unit with VitD insufficiency or deficiency treated with ergocalciferol. Patients were classified as either compliant or non-compliant with supplementation as determined by review of pharmacy records. The primary outcome was VitD levels 6 months after initiation of treatment and secondary outcomes were VitD levels at 11 months, bone/mineral and anemia parameters. Results: The population was predominately African-American (69%) and Hispanic (28%). There were 61 individuals in the compliant group and 35 individuals in the non-compliant group. The compliant group was older but otherwise similar in demographics and co-morbid conditions to the non-compliant group. After 6 months of treatment, the compliant group had a significant increase in VitD level (14.7 ± 6.0 to 28.7 ± 10.0 ng/ml, p < 0.0001) compared to the non-compliant group (14.7 ± 5.5 to 14.8 ± 7.1 ng/ml, p = 0.95). There were no differences in the incidence of hypercalcemia between the two groups. Except for a decrease in phosphorus in the compliant group (5.6 ± 1.6 to 4.9 ± 1.7 mg/dl, p = 0.004), there were no significant difference in bone/mineral or anemia parameters including dosing of darbepoetin. Conclusion: An ergocalciferol-prescribing strategy using the KDOQI guidelines for stage III-IV kidney disease in HD patients with VitD deficiency or insufficiency is inadequate to achieve repletion or maintenance of normal VitD levels.

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“…Table 2 summarizes the studies assessing changes in serum 25OHD and PTH with vitamin D supplementation. [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92] Supplementation with calcidiol in CKD stage 5D improved bone mineralization but had a limited effect on reducing serum PTH similar to non-CKD patients. 93,94 Several studies have also looked at the correlation between serum vitamin D level and BMD in CKD and non-CKD populations.…”

Section: Trabecular Bone Scorementioning

confidence: 99%

Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation

Pimentel

Ureña-Torres

Zillikens

et al. 2017

Kidney International

171

122

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Mineral and bone disease is omnipresent in patients with chronic kidney disease (CKD) and leads to a diverse range of clinical manifestations, including bone pain and fractures. The accumulation of traditional clinical risk factors, in addition to those related to CKD, enhances the risk of comorbidity and mortality. Despite significant advances in understanding bone disease in CKD, most clinical and biochemical targets used in clinical practice remain controversial, resulting in an undermanagement of bone fragility. Vitamin D supplementation is widely used, but only a few studies have shown beneficial effects and a reduced risk of fracture and mortality. The achievement of serum levels of 25-hydroxyvitamin D is recommended for CKD patients to reduce a high parathyroid hormone level, which is associated with skeletal fractures. Optimal control of parathyroid hormone also improves bone mineralization and lowers circulating bone biomarkers such as alkaline phosphatase and cross-linked collagen type I peptide. The potential value of more recent biomarkers such as sclerostin and fibroblast growth factor 23, as surrogates for bone fragility, is an encouraging new direction in clinical research but is far from being firmly established. This article reviews the literature related to the pathophysiological role of various mineral and biochemical factors involved in renal osteodystrophy. To better understand bone fragility in CKD, new information related to the impact of disturbances of mineral metabolism on bone strength is urgently needed. The combined expertise of clinicians from various medical disciplines appears crucial for the most successful prevention of fractures in these patients.Kidney International (2017) 92, 1343-1355; http://dx

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Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study

Abstract: Cholecalciferol is effective and safe, and does not negatively affect calcium, phosphorus, PTH levels and vascular calcifications. Additional studies are needed to compare the impacts of nutritional and active vitamin D agents on vascular calcification and mortality.

Cited by 72 publications

References 40 publications

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

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

Prevalence of 25-OH Vitamin D Deficiency in a Population of Hemodialysis Patients and Efficacy of an Oral Ergocalciferol Supplementation Regimen

Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation

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