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 P0898VITAMIN C STATUS MODIFIES PARATHYROID HORMONE SECRETION IN NON-DIALYZED CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ryuta Fujimura ◽  
SHOGO SHIBATA ◽  
Takechiyo Tokuda ◽  
Ayako Tanaka ◽  
Aya Mizumoto ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Vitamin C ◽  
Secondary Hyperparathyroidism ◽  
Hormone Secretion ◽  
Serum Vitamin ◽  
Serum Phosphate ◽  
Vitamin C Deficiency

Abstract Background and Aims Among patients with chronic kidney disease (CKD) at predialysis stage, there is a high incidence of secondary hyperparathyroidism. Metabolic changes associated with secondary hyperparathyroidism lead to renal osteodystrophy, including osteitis fibrosa, ectopic calcification, cardiovascular disease, and the risk of death, and serum parathyroid hormone levels are influenced by nutritional variables. Non-dialyzed CKD patients are especially prone to vitamin C deficiency because of dietary restrictions and malnutrition. Vitamin C is an important antioxidant and relates to the development and maintenance of bone tissues. However, the contribution of vitamin C deficiency to parathyroid hormone secretion is unknown. Here, we performed a single-center cross-sectional study in order to assess association of serum vitamin C and parathyroid hormone in non-dialyzed CKD patients. Method We had 280 consecutive patients who underwent serum vitamin C and serum intact parathyroid hormone (iPTH) measurement for screening purposes from January 1st, 2013 to November 30th, 2017. We analysed a total of 128 patients (71.3±11.6 year-old, 80 males) who had an estimated glomerular filtration rate (eGFR) that remained less than 60 mL/min/1.73m2 after 152 patients were excluded because of vitamin C or vitamin D supplementation, age &lt;20 years, dialysis, positive serostatus for HIV, hepatitis B or hepatitis C, chronic infection, or cancer. Results Twenty-three percent of the patients (n=29) had vitamin C levels&lt; 2.0 μg/mL (a range seen in very deficient subjects), 53% (n=68) had levels between 2.0 and 5.5 μg/mL, and 31 patients (24%) had vitamin C levels &gt;5.5 μg/mL, which is considered the upper limit of normal for the healthy population. Log(iPTH) significantly correlated with age (r=-0.238, p=0.00672), log(eGFR) (r=-0.625, p&lt;0.0001), serum calcium (r=-0.609, p&lt;0.0001), and serum phosphate (r=0.41, p&lt;0.0001), and had a tendency to correlate with serum albumin (r=-0.146, p=0.101). Low serum vitamin C was associated with higher serum iPTH (P=0.0005, one-way analysis of variance). In a multiple linear regression model with log(iPTH) as the dependent variable, and age, gender, log(eGFR), serum levels of calcium, phosphate, albumin, and vitamin C as independent variables, the inverse relationship of log(iPTH) and serum vitamin C was confirmed (R2 = 0.568, adjusted R2 = 0.543, P&lt;0.0001), along with other parameters influencing iPTH levels, including age, log(eGFR), serum calcium, and serum phosphate. Low vitamin C levels were also associated with increased serum alkaline phosphatase (r=-0.209, p=0.0179), a further indicator of the impact of vitamin C status on bone metabolism. Conclusion Vitamin C deficiency is prevalent in a significant proportion of non-dialyzed CKD patients. Low vitamin C levels contribute to secondary hyperparathyroidism, leading to increased bone turnover. This novel observation may result from effects of vitamin C on vitamin D metabolism, vitamin D binding in target tissues, and cAMP-linked signalling pathways in bone and parathyroid gland. Therapeutic intervention with supplemental vitamin C for secondary hyperparathyroidism might be a good strategy.

scholarly journals Treatment Failure of Active Vitamin D Therapy in Chronic Kidney Disease: Predictive Factors

2015 ◽  
Vol 42 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Mario Cozzolino ◽  
Adrian Covic ◽  
Blanca Martinez-Placencia ◽  
Konstantinos Xynos
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Treatment Failure ◽  
Serum Levels ◽  
Clinical Effects ◽  
Active Vitamin ◽  
Ipth Level ◽  
Active Vitamin D ◽  
Vitamin D Levels

Background: In patients with chronic kidney disease (CKD), impaired renal function leads to decreased vitamin D levels, which causes an increase in parathyroid hormone (PTH) production and contributes to the development of secondary hyperparathyroidism (SHPT). This may result in adverse clinical effects such as bone disorders, vascular calcification, cardiovascular disease, and increased mortality. Current treatment practices and associated outcomes with active vitamin D treatment in patients with CKD were reviewed with the objective to assess parameters (such as PTH and serum calcium levels) that may be used to define the failure of vitamin D treatment. Summary: Reports based on observational data have noted improved outcomes with active vitamin D treatment (calcitriol, paricalcitol, alfacalcidol, or doxercalciferol) in patients with CKD. Criteria for the identification of active vitamin D treatment failure are unclear from current guidelines, although up to 50% of patients may experience treatment failure eventually because of development of hypercalcemia or resistant SHPT, characterized by an elevated intact PTH (iPTH) level despite treatment. We propose a definition of vitamin D treatment failure as iPTH >600 pg/ml after 6 months of intravenous active vitamin D treatment and corrected total calcium serum levels >10.2 mg/dl, and review factors that may predict the response to vitamin D treatment. Key Message: Active vitamin D treatment failure is an important challenge in clinical practice. The aim of the proposed definition is to suggest a possible framework for hypothesis generation and to encourage further research into this common problem.

scholarly journals Secondary and tertiary hyperparathyroidism in chronic kidney disease

2017 ◽  
Vol 20 (2) ◽  
pp. 63-68 ◽  
Author(s):  
Lilit V. Egshatyan ◽  
Natalya G. Mokrisheva ◽  
Lyudmila Ya. Rozhinskaya
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Medical Therapy ◽  
Receptor Activation ◽  
Mineral Density ◽  
Tertiary Hyperparathyroidism ◽  
End Stage

In the treatment of secondary hyperparathyroidism of end-stage chronic kidney disease, vitamin D receptor activation and allosteric modulators of the calcium-sensing receptor – inhibit glandular hyperplasia, reduce parathyroid hormone levels, impact on bone turnover and mineral density. But the use of calcimimetic and vitamin D analogs or mimetics did not reduce the need for parathyroidectomy for refractory hyperparathyroidism. The enlarged parathyroid gland and gland nodular transformation became refractory to medical therapy and patient need for parathyroidectomy. Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone after a long period of secondary hyperparathyroidism and renal transplantation. In this article, we present the case of a Caucasian male with chronic kidney disease (end-stage on chronic hemodialysis and after kidney transplantation) and different forms of hyperparathyroidism (secondary and tertiary). Our case study shows that only a multi-interventional strategy is likely to be more effective treatment in cases of severe and refractory to medical therapy hyperparathyroidism.

scholarly journals P0891META-ANALYSIS OF NUTRITIONAL VITAMIN D FOR THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Joel Gunnarsson ◽  
Rosa Lauppe ◽  
Edelgard Kaiser ◽  
Marco Soro ◽  
Philipp Csomor
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Fixed Effects ◽  
Untreated Patient ◽  
Critical Role ◽  
Vitamin D Levels ◽  
Patient Groups ◽  
Nutritional Vitamin

Abstract Background and Aims Chronic kidney disease (CKD) is commonly associated with mineral and bone disorder (CKD-MBD). Secondary hyperparathyroidism (SHPT) is a critical component of CKD-MBD characterized by excessive PTH secretion and parathyroid hyperplasia. SHPT develops in CKD because of disturbances in CKD-MBD parameters such as increases in serum phosphate and fibroblast growth factor 23, and reductions in 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and serum calcium. Low vitamin D levels play a critical role in the development and progression of SHPT. Nutritional vitamin D (NVD) supplements are being frequently used to address SHPT, especially in early CKD. The objective of this meta-analysis (MA) was to evaluate the effectiveness of the NVDs cholecalciferol and ergocalciferol in reducing PTH and increasing 25(OH)D in patients with non-dialysis CKD (ND-CKD). Method A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the MA. All analyses were performed using both random and fixed effects models with inverted-variance weighting. Comparisons were made between the effects of NVDs relative to placebo-treated or untreated patients and between the baseline and end-of-study values of the patients treated with the NVDs, i.e. the effects in treated patients only. Results A total of 14 RCTs comprising 974 patients were included in the analyses. Overall reductions in PTH were small when compared to baseline (reduction of 10.95 pg/ml, 95 % confidence interval (CI): -15.99 to -5.91 pg/ml), while reductions in PTH were approximately three times larger when compared to placebo-treated or untreated patient groups (reduction of 34.35 pg/ml, 95 % CI:-47.47 to -21.24 pg/ml). This indicated a limited potential to actively lower PTH with NVDs as the relative effect on PTH when compared to placebo-treated or untreated patient groups was driven to a large degree by increases in PTH in the comparator arms. Treatment with NVDs tended to increase levels of 25(OH)D both when compared to placebo-treated or untreated patients (increase of 26.54 ng/ml, 95 % CI: 24.62 to 28.46 ng/ml) and when only the changes in treated patients were considered (increase of 21.49 ng/ml, 95 % CI: 20.54 to 22.44 ng/ml). However, large variations in effect sizes on levels of 25(OH)D were observed, making judgements about the size of any true treatment effect difficult. Average levels of 25(OH)D in treated patients at the end of the study period were &gt;30 ng/ml in all but two RCTs and &gt;50 ng/ml in only five of the included RCTs. No clear relationship was observed between study length (range: 4 to 144 weeks) or doses administered (range: 14 000 to 75 000 UI weekly average) and effects on 25(OH)D or PTH. Conclusion Our results suggest that treatment with NVDs is not efficacious to reliably and consistently lower PTH in ND-CKD patients with SHPT. Although treatment with NVDs can potentially be used to correct vitamin D insufficiency, our results suggest that the potential of NVD treatment to raise 25(OH)D levels to &gt;50 ng/ml, a level needed to reduce PTH, is limited.

scholarly journals Prevalence of Decreased Vitamin D Levels is High among Veterans with Diabetes and/or CKD

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Subhashini Yaturu ◽  
Jared Davis
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vitamin D Deficiency ◽  
Vitamin D Insufficiency ◽  
Record System ◽  
Vitamin D Levels ◽  
History Of ◽  
Computerized Patient Record ◽  
25 Oh Vitamin D

Objective. Vitamin D deficiency is associated with a variety of skeletal and extraskeletal problems. The aim of this study was to evaluate the prevalence of vitamin D deficiency among veterans in sunny Louisiana. Methods. Using the VA computerized patient record system, we searched for all 25 (OH) Vitamin D and 1, 25 (OH) vitamin D levels that were measured between 2007 and 2009. The information collected for each patient included age, body mass index, creatinine, history of diabetes and hypertension, and levels of vitamin D and PTH. We determined the number of individuals who were vitamin D insufficient and deficient. Results. Among 2990 studies evaluated, the mean concentration of 25 (OH) D was  ng/mL, and that of 1, 25 (OH) vitamin D was  ng/mL. Among them, only 695 subjects (23%) had normal values, while 889 (30%) had insufficiency, and 1405 (47%) had deficiency. Subjects with diabetes (1041) had significantly () lower levels (21 and 25 ng/mL) of both 25 (OH) and 1,25 (OH) vitamin D compared to subjects without diabetes (23 and 32 ng/mL). Similarly, subjects with chronic kidney disease (1128) had much lower vitamin D levels than subjects without CKD. Among subjects with diabetes, those with chronic kidney disease (512) had much lower levels of both 25 (OH) and 1,25 (OH) vitamin D than with those with normal creatinine levels. Conclusions. We conclude that vitamin D insufficiency and deficiency is highly prevalent in veterans, more so among subjects with diabetes and/or CKD.

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.

STUDY THE SERUM VITAMIN D LEVELS IN PATIENTS OF CHRONIC KIDNEY DISEASE

2021 ◽  
pp. 1-3
Author(s):  
Brahmarshi Das ◽  
Narendranath Hait ◽  
Jayanta Kumar Rout ◽  
Debarshi Jana
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Serum Vitamin ◽  
Hypovitaminosis D ◽  
Newly Diagnosed ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
The Mean

INTRODUCTION: Chronic Kidney Disease (CKD) is dened as a disease characterized by alterations in either kidney structure or function or both for a minimum of 3 months duration. Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of kidney 1 function over a period of months or years. Early on there are typically no symptoms. Later, leg swelling, feeling tired, vomiting, loss of appetite, or 1 confusion may develop. Complications may include heart disease, high blood pressure, bone disease, or anemia. AIM AND OBJECTIVES: Study of Prevalence of hypovitaminosis D in patients of chronic kidney diseases. Search for commonest etiology of hypovitaminosis D in CKD. MATERIALAND METHOD: A Cross-sectional study on 100 cases of newly diagnosed Chronic Kidney Disease patients and matched control subjects is undertaken to study the prevalence of Vitamin D deciency in CKD population and correlation between their serum 25-OH-vitamin D level. 100 Patients who are newly diagnosed as CKD are selected after proper initial screening at Midnapore Medical College, Paschim Medinipur. RESULT AND ANALYSIS: Our study showed that in non-dialysis Syndrome the mean VitD (mean± s.d.) of patients was 25.6620 ± 8.5476. In dialysis the mean VitD (mean± s.d.) of patients was 10.9476 ± 2.6508. Difference of mean VitD in Dialysis vs Non-Dialysis was statistically signicant (p<0.0001). In eGFR 1 (<15) the mean VitD (mean± s.d.) of patients was 11.1130 ± 2.9562. In eGFR2 (15-30) the mean VitD (mean± s.d.) of patients was 24.0750 ± 8.2995. In eGFR3 (31-45) the mean VitD (mean± s.d.) of patients was 26.8296 ± 7.3646. In eGFR4 (>45) the mean VitD (mean± s.d.) of patients was 36.3167 ± 4.9898. Difference of mean VitDin eGFR was statistically signicant (p<0.0001). SUMMARYAND CONCLUSION: Vitamin-D deciency more pronounced in advanced stages of CKD. Vitamin-D deciency was most prevalent in female gender, younger age group and connective tissue disorder. Vitamin-D deciency was more marked in hemodialysis patients compared to non-dialysis CKD patients.

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