Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease

2016 ◽  
Vol 44 (4) ◽  
pp. 316-325 ◽  
Author(s):  
Stuart M. Sprague ◽  
Paul W. Crawford ◽  
Joel Z. Melnick ◽  
Stephen A. Strugnell ◽  
Shaukat Ali ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Extended Release ◽  
Vitamin D Insufficiency ◽  
Double Blind ◽  
Hydroxyvitamin D ◽  
Ckd Stage ◽  
25 Hydroxyvitamin D

Background/Aims: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Methods: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. Results: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Conclusion: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

scholarly journals Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

2014 ◽  
Vol 40 (6) ◽  
pp. 535-545 ◽  
Author(s):  
Stuart M. Sprague ◽  
Arnold L. Silva ◽  
Fahd Al-Saghir ◽  
Radhika Damle ◽  
Samir P. Tabash ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Insufficiency ◽  
Modified Release

scholarly journals The Association between 25-Hydroxyvitamin D and Hemoglobin A1c Levels in Patients with Type 2 Diabetes and Stage 1–5 Chronic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Farshad Kajbaf ◽  
Romuald Mentaverri ◽  
Momar Diouf ◽  
Albert Fournier ◽  
Said Kamel ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Hemoglobin A1c ◽  
Diabetic Patients ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Stage 1 ◽  
Hba1c Levels

Aim. To examine the relationship between plasma 25-hydroxyvitamin D (25(OH)D) levels and blood hemoglobin A1c (HbA1c) levels in diabetic patients at various stages of chronic kidney disease (CKD).Methods. We screened for data collected between 2003 and 2012. The correlation between 25(OH)D and HbA1c levels was studied in patients categorized according to the severity of CKD and their vitamin D status. A multivariate linear regression model was used to determine whether 25(OH)D and HbA1c levels were independently associated after adjustment for a number of covariates (including erythrocyte metformin levels).Results. We identified 542 reports from 245 patients. The mean HbA1c value was6.7±1.0% in vitamin D sufficiency,7.3±1.5% in insufficiency, and8.4±2.0% in deficiency (P<0.0001). There was a negative correlation between 25(OH)D and HbA1c levels for the population as a whole (r=-0.387,P<0.0001) and in the CKD severity subgroups (r=-0.384,P<0.0001andr=-0.333,P<0.0001for CKD stages 1–3 and 4-5, resp.). In the multivariate analysis, the 25(OH)D level was the only factor associated with HbA1c (P<0.0001).Conclusion. 25(OH)D levels were negatively correlated with HbA1c levels independently of study covariates.

scholarly journals Extended-release calcifediol in stage 3–4 chronic kidney disease: a new therapy for the treatment of secondary hyperparathyroidism associated with hypovitaminosis D

2021 ◽  
Author(s):  
Mario Cozzolino ◽  
Paola Minghetti ◽  
Pierluigi Navarra
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Extended Release ◽  
Hypovitaminosis D ◽  
Active Vitamin ◽  
Vitamin D Levels ◽  
25 Oh Vitamin D

AbstractA high percentage of patients with chronic kidney disease have hypovitaminosis D, which is a driver of secondary hyperparathyroidism and an important factor in chronic kidney disease-mineral and bone disorder. Vitamin D deficiency (serum total 25-OH vitamin D levels < 30 ng/mL) occurs early in the course of chronic kidney disease and treatment guidelines recommend early intervention to restore 25-OH vitamin D levels as a first step to prevent/delay the onset/progression of secondary hyperparathyroidism. The vitamin D forms administered to replace 25-OH vitamin D include cholecalciferol, ergocalciferol, and immediate- or extended-release formulations of calcifediol. Most patients with intermediate-stage chronic kidney disease will develop secondary hyperparathyroidism before dialysis is required. Control of parathyroid hormone levels becomes a major focus of therapy in these patients. This article focuses on the position of extended-release calcifediol in the treatment of patients with stage 3–4 chronic kidney disease and secondary hyperparathyroidism with hypovitaminosis D. Several characteristics of extended-release calcifediol support its use in the intermediate stages of chronic kidney disease. The pharmacokinetics of extended-release calcifediol make it effective for replenishing 25-OH vitamin D levels, with minimal impact on vitamin D catabolism from fibroblast-growth factor-23 and CYP24A1 upregulation. Extended-release calcifediol increases circulating 25-OH vitamin D levels in a dose-dependent manner and lowers parathyroid hormone levels by a clinically relevant extent, comparable to what can be achieved by administering active vitamin D analogues, though with a lower risk of hypercalcaemia and hyperphosphataemia. Active vitamin D analogues are reserved for patients undergoing dialysis or pre-dialysis patients with severe progressive secondary hyperparathyroidism. Graphic abstract

scholarly journals 25-Hydroxyvitamin D and Severity of Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Ahmad Chitsaz ◽  
Mohammad Maracy ◽  
Keivan Basiri ◽  
Maryam Izadi Boroujeni ◽  
Amir Pouya Tanhaei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Vitamin D ◽  
Parkinson's Disease ◽  
Cross Sectional Study ◽  
Vitamin D Insufficiency ◽  
Early Disease ◽  
Double Blind ◽  
Cross Sectional ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

Introduction. A role for vitamin D deficiency in Parkinson’s disease (PD) has recently been proposed. Given the growing body of evidence for the association of vitamin D with several neurodegenerative disorders and unavailability of any published study in the Middle East, the present study is aimed to determine the associations of circulating 25-hydroxyvitamin D (25OHD) levels with the severity of PD in an Iranian sample.Methods. In 109 patients, the severity of PD was evaluated by using Hoehn & Yahr (HR) stages and Unified Parkinson’s Disease Rating Stage (UPDRS) Part III compared with 25OHD level in a double-blind and cross-sectional study.Results. Mean ± SD levels of 25OHD were 28.5 ± 1.4 and 27.1 ± 1.5, for males and females, respectively. Also, 38.4% of the patients showed deficiency levels of 25OHD (<20 ng/mL), and 72.8% had insufficient levels (<30 ng/mL). High prevalence of 25OHD insufficiency in subjects with early disease was not associated with HR stage and UPDRS scores even after multivariate adjustment for possible confounders including disease duration.Conclusions. These findings are consistent with the possibility that vitamin D status does not seem to deteriorate during the early disease stages of PD. Further studies are needed to reveal the natural role and significance of vitamin D insufficiency in PD.

scholarly journals Efficacy and Safety of Cinacalcet in Chronic Kidney Disease Stage III and IV

2009 ◽  
Vol 1 ◽  
pp. CMT.S3189
Author(s):  
Aiji Yajima ◽  
Andreas Pasch ◽  
Kosaku Nitta
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Chronic Kidney Disease Stage ◽  
Stage Iii ◽  
Disease Stage ◽  
Control Serum ◽  
Ckd Stage ◽  
Cinacalcet Hydrochloride

Treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) stage III and IV with vitamin D sterols is useful to maintain optimal parathyroid hormone (PTH) levels and thereby, reduces the severity of bone abnormalities caused by high PTH levels. However, it should be borne in mind that serum calcium (Ca) levels may easily increase as bone turnover is easily suppressed due to diffuse or early nodular parathyroid tissue in these patients. Furthermore, an elevated risk of cardiovascular disease due to advanced atherosclerosis associated with both secondary hyperparathyroidism and the administration of vitamin D sterols has been reported in patients with moderate to severe CKD, resulting in a high mortality in these patients. In order to control serum Ca levels, therefore, additional use of cinacalcet hydrochloride may be useful. However, acute reduction of serum Ca levels and chronic hyperphosphatemia should be avoided; therefore, the doses of phosphorus (P) binders should be increased or the initiation of low doses of vitamin D sterols may be favorable in patients with stage III and IV CKD receiving cinacalcet hydrochloride. The phosphaturic effect of FGF-23 after treatment with cinacalcet is estimated to be small as compared with that of vitamin D in moderate to severe CKD patients, therefore, evaluation of osteocytes should be performed in patients with secondary hyperparathyroidism treated with cinacalcet hydrochloride.

scholarly journals Prevalence and Prognostic Implications of Vitamin D Deficiency in Chronic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yoshitsugu Obi ◽  
Takayuki Hamano ◽  
Yoshitaka Isaka
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vitamin D Deficiency ◽  
Mineral Metabolism ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Definition Of

Vitamin D is an important nutrient involved in bone mineral metabolism, and vitamin D status is reflected by serum total 25-hydroxyvitamin D (25[OH]D) concentrations. Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD), and nutritional vitamin D supplementation decreases elevated parathyroid hormone concentrations in subgroups of these patients. Furthermore, vitamin D is supposed to have pleiotropic effects on various diseases such as cardiovascular diseases, malignancies, infectious diseases, diabetes, and autoimmune diseases. Indeed, there is cumulative evidence showing the associations of low vitamin D with the development and progression of CKD, cardiovascular complication, and high mortality. Recently, genetic polymorphisms in vitamin D-binding protein have received great attention because they largely affect bioavailable 25(OH)D concentrations. This finding suggests that the serum total 25(OH)D concentrations would not be comparable among different gene polymorphisms and thus may be inappropriate as an index of vitamin D status. This finding may refute the conventional definition of vitamin D status based solely on serum total 25(OH)D concentrations.

scholarly journals Where are we now? Emerging opportunities and challenges in the management of secondary hyperparathyroidism in patients with non-dialysis chronic kidney disease

2021 ◽  
Author(s):  
Markus Ketteler ◽  
Patrice Ambühl
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Extended Release ◽  
Therapeutic Agents ◽  
Management Approach ◽  
Optimal Management ◽  
Release Formulation ◽  
Extended Release Formulation ◽  
Ckd Stage

Abstract Rising levels of parathyroid hormone (PTH) are common in patients with chronic kidney disease (CKD) not on dialysis and are associated with an elevated risk of morbidity (including progression to dialysis) and mortality. However, there are several challenges for the clinical management of secondary hyperparathyroidism (SHPT) in this population. While no recognised target level for PTH currently exists, it is accepted that patients with non-dialysis CKD should receive early and regular monitoring of PTH from CKD stage G3a. However, studies indicate that adherence to monitoring recommendations in non-dialysis CKD may be suboptimal. SHPT is linked to vitamin D [25(OH)D] insufficiency in non-dialysis CKD, and correction of low 25(OH)D levels is a recognised management approach. A second challenge is that target 25(OH)D levels are unclear in this population, with recent evidence suggesting that the level of 25(OH)D above which suppression of PTH progressively diminishes may be considerably higher than that recommended for the general population. Few therapeutic agents are licensed for use in non-dialysis CKD patients with SHPT and optimal management remains controversial. Novel approaches include the development of calcifediol in an extended-release formulation, which has been shown to increase 25(OH)D gradually and provide a physiologically-regulated increase in 1,25(OH)2D that can reliably lower PTH in CKD stage G3–G4 without clinically meaningful increases in serum calcium and phosphate levels. Additional studies would be beneficial to assess the comparative effects of available treatments, and to more clearly elucidate the overall benefits of lowering PTH in non-dialysis CKD, particularly in terms of hard clinical outcomes. Graphic abstract

scholarly journals Vitamin D-Fortified Bread Is as Effective as Supplement in Improving Vitamin D Status: A Randomized Clinical Trial

2016 ◽  
Vol 101 (6) ◽  
pp. 2511-2519 ◽  
Author(s):  
Bahareh Nikooyeh ◽  
Tirang R. Neyestani ◽  
Maliheh Zahedirad ◽  
Mehrdad Mohammadi ◽  
S. Hedayat Hosseini ◽  
...  
Keyword(s):  
Vitamin D ◽  
Controlled Trial ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Concentration ◽  
Daily Consumption ◽  
Double Blind ◽  
Hydroxyvitamin D ◽  
Group Reduction ◽  
25 Hydroxyvitamin D

Abstract Context: Bread can potentially be a suitable vehicle for fortification with vitamin D. Objective: This study was undertaken to evaluate the following: 1) the bioavailability of vitamin D from the fortified Iranian bread and 2) the possible effects of daily consumption of the fortified bread on certain health aspects. Design, Setting, and Participants: This was a randomized, double-blind, placebo-controlled trial conducted over 8 weeks in 90 healthy subjects aged 20–60 years. Intervention: Subjects were randomly allocated to one of three groups: 1) fortified bread (FP; 50 g bread fortified with 25 μg vitamin D3 plus placebo daily; n = 30); 2) supplement (SP; 50 g plain bread plus 25 μg vitamin D supplement daily; n = 30); and 3) control (CP; 50 g plain bread plus placebo daily; n = 30). Outcome Measures: Initial and final anthropometric and biochemical assessments were performed. Results: The within-group changes of serum 25-hydroxyvitamin D concentrations were 39.0 ± 22.6 (P &lt; .001), 28.9 ± 31.2 (P &lt; .001), and −9.2 ± 12.3 nmol/L in the FP, SP, and CP groups, respectively. Only in FP and SP groups, serum intact PTH concentrations decreased approximately 13.5% and 14.5%, respectively. Visceral fat also showed a significant decrement in FP (−1.05% ± 1.4%; P ≤ .001) and SP (−0.96% ± 1.7%; P = .006). Serum low-density lipoprotein cholesterol concentration showed a within-group reduction in FP (−10.4 ± 11.2 mg/dL; P &lt; .001) and an insignificant decrement in SP (−6.6 ± 20.2 mg/dL; P = .083). Serum high-density lipoprotein increased in both vitamin D-supplemented groups (FP: 9.7 ± 7.6 vs SP: 5.7 ± 6.7 mg/dL; P &lt; .001). Conclusion: Vitamin D-fortified bread could be potentially effective in raising circulating 25-hydroxyvitamin D levels of the population to nearly adequate levels.

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