cholecalciferol and Renal-Insufficiency--Chronic

To review the available literature regarding a possible relationship between vitamin D and bone marrow adipose tissue (BMAT), and to identify future avenues of research that warrant attention.. Results from in vivo animal and human studies all support the hypothesis that vitamin D can suppress BMAT expansion. This is achieved by antagonizing adipogenesis in bone marrow stromal cells, through inhibition of PPARγ2 activity and stimulation of pro-osteogenic Wnt signalling. However, our understanding of the functions of BMAT is still evolving, and studies on the role of vitamin D in modulating BMAT function are lacking. In addition, many diseases and chronic conditions are associated with low vitamin D status and low bone mineral density (BMD), but BMAT expansion has not been studied in these patient populations. Vitamin D suppresses BMAT expansion, but its role in modulating BMAT function is poorly understood.

Topics: Adipogenesis; Adipose Tissue; Aging; Animals; Bone Marrow; Cholecalciferol; Diabetes Mellitus, Type 2; Humans; Mesenchymal Stem Cells; Obesity; Osteogenesis; Osteoporosis; PPAR gamma; Receptors, Calcitriol; Renal Insufficiency, Chronic; Vitamin D; Wnt Signaling Pathway

Intradialytic exercise (IDE) is not yet a routine practice for hemodialysis patients, the lack of guidelines supporting it being a major reason. This systematic review and meta-analysis of aerobic IDE interventions examined the efficacy of IDE regarding quality of life (QOL), serum phosphorus, dialysis efficiency, inflammatory status, vitamin D3, parathyroid hormone, intake of phosphate binders, mortality and hospitalization rate.. Pubmed, Medline (Ovid), Embase (Ovid), Cochrane, and Cinahl (EBSCO) databases were searched to retrieve studies up to June 12, 2018. A manual reference search was also performed. Studies were included if they evaluated (a) aerobic IDE effect on at least one of our study parameters, (b) adult hemodialysis patients, (c) patients for > 1 month.. Twenty-two studies were retrieved (706 participants), of which 12 were eligible for meta-analysis. Aerobic IDE had a significant positive effect on the QOL physical component score (QOL-PSC) and on mental component score (QOL-MCS) of SF36, but not on serum phosphorus or Kt/V.. IDE incorporation into clinical practice has a significant positive effect on QOL-PSC and QOL-MCS. In the reviewed studies, IDE did not result in any health hazard in hemodialysis patients. Nevertheless, future research should assess the long-term effectiveness and safety of IDE. The limitations of this review include the lack of quality analysis of the studies, the limited number of studies that could be included in the meta-analysis, the diversity in the exercise intensity, duration and modality, and the limited data for several outcomes.. CRD42016052062.

Topics: C-Reactive Protein; Chelating Agents; Cholecalciferol; Exercise; Hospitalization; Humans; Inflammation; Parathyroid Hormone; Phosphorus; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic

Vitamin D is recognized to play an essential role in health and disease. In kidney disease, vitamin D analogs have gained recognition for their involvement and potential therapeutic importance. Nephrologists are aware of the use of oral native vitamin D supplementation, however, uncertainty still exists with regard to the use of this treatment option in chronic kidney disease as well as clinical settings related to chronic kidney disease, where vitamin D supplementation may be an appropriate therapeutic choice. Two consecutive meetings were held in Florence in July and November 2016 comprising six experts in kidney disease (N = 3) and bone mineral metabolism (N = 3) to discuss a range of unresolved issues related to the use of cholecalciferol in chronic kidney disease. The panel focused on the following six key areas where issues relating to the use of oral vitamin D remain controversial: (1) vitamin D and parathyroid hormone levels in the general population, (2) cholecalciferol in chronic kidney disease, (3) vitamin D in cardiovascular disease, (4) vitamin D and renal bone disease, (5) vitamin D in rheumatological diseases affecting the kidney, (6) vitamin D and kidney transplantation.

Topics: Cholecalciferol; Humans; Renal Insufficiency, Chronic; Vitamin D Deficiency

Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue. As in the general population, this condition is associated with increased morbidity and poor outcomes. Together with the progressive decline of serum calcitriol, vitamin D deficiency leads to secondary hyperparathyroidism (SHPT) and its complications, tertiary hyperparathyroidism and hypercalcemia, which require surgical parathyroidectomy or calcimimetics. Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease Improving Global Outcomes (KDIGO) experts have recognized that vitamin D insufficiency and deficiency should be avoided in CKD and dialysis patients by using supplementation to prevent SHPT. Many vitamin D supplementation regimens using either ergocalciferol or cholecalciferol daily, weekly or monthly have been reported. The benefit of native vitamin D supplementation remains debatable because observational studies suggest that vitamin D receptor activator (VDRA) use is associated with better outcomes and it is more efficient for decreasing the serum parathormone (PTH) levels. Vitamin D has pleiotropic effects on the immune, cardiovascular and neurological systems and on antineoplastic activity. Extra-renal organs possess the enzymatic capacity to convert 25(OH)D to 1,25(OH)₂D. Despite many unanswered questions, much data support vitamin D use in renal patients. This article emphasizes the role of native vitamin D replacement during all-phases of CKD together with VDRA when SHPT persists.

Topics: Cholecalciferol; Dialysis; Dietary Supplements; Ergocalciferols; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Parathyroid Hormone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vitamin D Deficiency

Deranged vitamin D metabolism represents an active trigger of secondary hyperparathyroidism (SHPT) in CKD. Correction of 25(OH)D deficiency by nutritional Vitamin D administration is suggested by KDIGO guidelines, to prevent and treat SHPT in CKD stage G3-G5 and G1T-G5T patients, although with a still inconsistent background. Nutritional vitamin D is available as cholecalciferol, ergocalciferol, or calcifediol. Superiority of calcifediol in increasing 25(OH)D levels has been suggested due to its better bioavailability. The safer pharmacokinetic of the recent modified-release (MR) formulation of calcifediol was effective in replenishing 25(OH)D levels with minimal impact on vitamin D catabolism and fibroblast-growth factor-23 (FGF-23) activation. Areas covered: the review discusses utility of calcifediol for treating SHPT in different CKD stages under physiology driven approach, focusing on vitamin D metabolism, guidelines suggestions and comparison between clinical effects on SHPT elicited by calcifediol, cholecalciferol and ergocalciferol. Expert commentary: although optimal targets of 25(OH)D and parathormone remain uncertain, calcifediol, especially in its newer MR formulation, may represent an intriguing option to combine an efficacious correction of 25(OH)D deficit and SHPT, with a limited impact on vitamin D catabolism and FGF-23 activation. Newer data are required to better explore the role of MR calcifediol in treating SHPT.

Topics: Animals; Biological Availability; Calcifediol; Cholecalciferol; Delayed-Action Preparations; Ergocalciferols; Fibroblast Growth Factor-23; Humans; Hyperparathyroidism, Secondary; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Vitamin D; Vitamins

Osteoporotic fractures are common in patients with chronic kidney disease (CKD). Morbidity and mortality are higher in CKD patients with a fracture than in the general population. The assessment of bone mineral density for fracture prediction may be useful at all CKD stages. It should be considered when this influences treatment decisions. Vitamin D deficiency is common in patients with CKD, particularly in patients with proteinuria, due to loss of 25-hydroxyvitamin D and its binding protein. Vitamin D supplementation should be prescribed early in the course of renal disease. For treatment and prevention of vitamin D deficiency in CKD patients cholecalciferol 800 IU/day or the equivalent per month is recommended just as in the general population.

Topics: Bone Density Conservation Agents; Cholecalciferol; Humans; Osteoporosis; Osteoporotic Fractures; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

The prevalence of vitamin D deficiency in hemodialysis patients is high. While most hemodialysis patients are treated with activated vitamin D (1,25[OH]2D) to prevent renal osteodystrophy, clinical practices of the screening and treatment of 25(OH)2D deficiency are highly variable. It is unclear if nutritional vitamin D supplementation with D2 or D3 provides an additional clinical benefit beyond that provided by activated vitamin D treatment in this population.. We will conduct a systematic review of nutritional vitamin D (D2/D3) supplementation and health-related outcomes in hemodialysis patients according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary objective is to assess the impact of nutritional vitamin D supplementation on clinical outcomes relevant in hemodialysis patients, such as mortality, cardiovascular events, infections, and fractures. Secondary outcomes will include anemia, hyperparathyroidism, medication use (erythrocyte-stimulating agents, activated vitamin D), and quality of life. We will search MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov for randomized, controlled trials of nutritional vitamin D supplementation (ergocalciferol/D2 or cholecalciferol/D3) in chronic hemodialysis patients. The Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies. We will perform meta-analyses using standard techniques for the outcomes listed above if pooling is deemed appropriate/sufficient. The results of this systematic review may highlight gaps in our knowledge of the relevance of nutritional vitamin D in end-stage renal disease, allowing for the informed design of clinical trials assessing the impact of nutritional vitamin D therapy in the hemodialysis population in the future.. PROSPERO CRD42014013931.

Topics: Cardiovascular Diseases; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Protocols; Dietary Supplements; Ergocalciferols; Fractures, Bone; Humans; Infections; Renal Dialysis; Renal Insufficiency, Chronic; Research Design; Systematic Reviews as Topic; Vitamin D Deficiency; Vitamins

Renal osteodystrophy is the damage of bone morphology by CKD and treatment and occurred abnormal bone metabolism through renal dysfunction. It demonstrated that the control of P and Ca improves to normalization of mineral metabolism. Protein energy wasting and malnutrition are common in patients with CKD stage 5 and has been associated with life prognosis. In CKD patients, nutritional management is a critical role of treatment. Also it may be important of nutritional management that control P and Ca and improve nutritional status in renal osteodystrophy patients.

Topics: Bone and Bones; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphonates; Humans; Nutrition Therapy; Nutritional Status; Osteoporosis; Phosphorus; Prognosis; Protein-Energy Malnutrition; Renal Insufficiency, Chronic

Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease (CKD) population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children (CKiD) and the Cardiovascular Comorbidity in Children with CKD (4 C) should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes.

Topics: Child; Cholecalciferol; Dietary Supplements; Ergocalciferols; Growth Disorders; Humans; Hyperparathyroidism, Secondary; Kidney; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

The development of chronic kidney disease (CKD) is accompanied by a progressive decrease in the ability to produce 1,25-dihydroxyvitamin D. Pharmacological replacement with active vitamin D therefore has been a cornerstone of secondary hyperparathyroidism therapy in the end-stage renal disease population treated by long-term dialysis. Recent evidence suggests that extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D may have significant biological roles beyond those traditionally ascribed to vitamin D. Furthermore, low 25-hydroxyvitamin D levels are common in patients with all stages of CKD. This article focuses on the role of nutritional vitamin D replacement in CKD and aims to review vitamin D biology and summarize the existing literature regarding nutritional vitamin D replacement in these populations. Based on the current state of the evidence, we provide suggestions for clinical practice and address areas of uncertainty that need further research.

Topics: Aged; Calcifediol; Cholecalciferol; Ergocalciferols; Female; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD).. This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores.. 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r =  - 0.4, p < 0.001).. Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Alkaline Phosphatase; Biomarkers; Child; Cholecalciferol; Dietary Supplements; Female; Humans; Male; Renal Insufficiency, Chronic; Vitamin D Deficiency

Hepcidin is considered to play a central role in the pathophysiology of renal anemia. Recent studies in healthy individuals have demonstrated a suppressive effect of vitamin D (VD) on the expression of hepcidin. In this post-hoc analysis based on a randomized controlled study, we evaluated the effect of supplementing chronic kidney disease (CKD) patients (stage G3-G4) with a high daily dose of native VD on serum levels of hepcidin-25, the hepcidin/ferritin ratio, as well as on markers of erythropoiesis.. Patients with CKD stage G3-G4 included in a double blind, randomized, placebo (PBO) controlled study with available hepcidin measurements were analyzed. Study subjects received either 8000 international units (IU) of cholecalciferol daily or PBO for 12 weeks. We evaluated the change in markers of hepcidin expression, erythropoiesis, and iron status from baseline to week 12 and compared the change between the groups.. Eighty five patients completed the study. Calcitriol, but not 25-hydroxyvitamin D (25(OH) D), was inversely correlated with serum levels of hepcidin-25 (rho = -0,38; p =  < 0, 01 and rho = -0,02; p = 0, 89, respectively) at baseline. Supplementation with VD significantly raised the serum concentration of serum 25(OH)D in the treatment group (from 54 (39-71) to 156 (120-190) nmol/L; p =  < 0, 01)) but had no effect on any of the markers of hepcidin, erythropoiesis, or iron status in the entire cohort. However, we did observe an increase in hemoglobin (HB) levels and transferrin saturation (TSAT) as compared to the PBO group in a subgroup of patients with low baseline 25(OH)D levels (< 56 nmol/L). In contrast, in patients with high baseline 25(OH)D values (≥ 56 nmol/L), VD supplementation associated with a decrease in HB levels and TSAT (p = 0,056) within the VD group in addition to a decrease in hepcidin levels as compared to the PBO group.. High-dose VD supplementation had no discernible effect on markers of hepcidin or erythropoiesis in the entire study cohort. However, in patients with low baseline 25(OH)D levels, high-dose VD supplementation associated with beneficial effects on erythropoiesis and iron availability. In contrast, in patients with elevated baseline 25(OH)D levels, high-dose VD supplementation resulted in a decrease in hepcidin levels, most likely due to a deterioration in iron status.

Topics: Cholecalciferol; Dietary Supplements; Erythropoiesis; Hepcidins; Humans; Iron; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

This study was performed to evaluate the efficacy of cholecalciferol in improving renal and vascular functions in vitamin D-deficient patients with type 2 diabetes mellitus (T2DM) along with chronic kidney disease (CKD). One hundred patients (18 - 65 years), having T2DM along with CKD (stage IIIA and IIIB) and hypovitaminosis D were randomized (1:1) to receive either oral cholecalciferol 60,000 IU (Group A) or placebo (Group B) weekly for 8 weeks along with standard background treatment. They were followed up for another 24 weeks. Various parameters of renal and vascular functions were compared. Except for serum calcium and phosphate levels which were significantly higher in Group A (

Topics: Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Humans; Pulse Wave Analysis; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p<0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p<0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogeni

Topics: Angiopoietin-1; Angiopoietin-2; Biomarkers; Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Topics: Biomarkers; Black or African American; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Cholecalciferol; Fibroblast Growth Factors; Humans; Parathyroid Hormone; Plasminogen Activator Inhibitor 1; Pulse Wave Analysis; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins

The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ≥30 ng/mL in children with CKD stages 2-4.. An open-label, multicentre randomized controlled trial randomized children with 25OHD concentrations <30 ng/mL in 1:1:1 to oral cholecalciferol 3000 IU daily, 25 000 IU weekly or 100 000 IU monthly for 3 months (maximum three intensive courses). In those with 25OHD ≥30 ng/mL, 1000 IU cholecalciferol daily (maintenance course) was given for up to 9 months. Primary outcome was achieving 25OHD ≥30 ng/mL at the end of intensive phase treatment.. Ninety children were randomized to daily (n = 30), weekly (n = 29) or monthly (n = 31) treatment groups. At the end of intensive phase, 70/90 (77.8%) achieved 25OHD ≥30 ng/mL; 25OHD concentrations were comparable between groups (median 44.3, 39.4 and 39.3 ng/mL for daily, weekly and monthly groups, respectively; P = 0.24) with no difference between groups for time to achieve 25OHD ≥30 ng/mL (P = 0.28). There was no change in calcium, phosphorus and parathyroid hormone, but fibroblast growth factor 23 (P = 0.002) and klotho (P = 0.001) concentrations significantly increased and were comparable in all treatment groups. Irrespective of dosing regimen, children with glomerular disease had 25OHD concentrations lower than non-glomerular disease (25.8 versus 41.8 ng/mL; P = 0.007). One child had a 25OHD concentration of 134 ng/mL, and 5.5% had hypercalcemia without symptoms of toxicity.. Intensive treatment with oral cholecalciferol as daily, weekly or monthly regimens achieved similar 25OHD concentrations between treatment groups, without toxicity. Children with glomerular disease required higher doses of cholecalciferol compared with those with non-glomerular disease.

Topics: Child; Cholecalciferol; Dietary Supplements; Humans; Hypercalcemia; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D Deficiency

Vascular calcification is common in chronic kidney disease (CKD) and associated with increased cardiovascular mortality. Aldosterone has been implicated as an augmenting factor in the progression of vascular calcification. The present study further explored putative beneficial effects of aldosterone inhibition by the mineralocorticoid receptor antagonist spironolactone on vascular calcification in CKD.. Serum calcification propensity was determined in serum samples from the MiREnDa trial, a prospective, randomized controlled clinical trial to investigate efficacy and safety of spironolactone in maintenance hemodialysis patients. Experiments were conducted in mice with subtotal nephrectomy and cholecalciferol treatment, and in calcifying primary human aortic smooth muscle cells (HAoSMCs).. Serum calcification propensity was improved by spironolactone treatment in patients on hemodialysis from the MiREnDa trial. In mouse models and HAoSMCs, spironolactone treatment ameliorated vascular calcification and expression of osteogenic markers.. These observations support a putative benefit of spironolactone treatment in CKD-associated vascular calcification. Further research is required to investigate possible improvements in cardiovascular outcomes by spironolactone and whether the benefits outweigh the risks in patients with CKD.

Topics: Aldosterone; Alkaline Phosphatase; Animals; Aorta; Biomarkers; Cholecalciferol; Core Binding Factor Alpha 1 Subunit; Female; Gene Expression; Humans; Kidney; Mice; Mice, Inbred DBA; Mineralocorticoid Receptor Antagonists; Myocytes, Smooth Muscle; Nephrectomy; Primary Cell Culture; Prospective Studies; Receptors, Mineralocorticoid; Renal Dialysis; Renal Insufficiency, Chronic; Spironolactone; Transcription Factor Pit-1; Vascular Calcification

To compare the differences in musculoskeletal health with vitamin D alone in comparison with vitamin D with physical activity (PA) among chronic kidney disease (CKD) patients.. An open labeled, randomized, controlled trial was conducted at two tertiary care centers in Pakistan. Patients with CKD stage 2-4 and vitamin D deficiency (<20 ng/mL) were recruited in the trial. Both the arms were given oral vitamin D (cholecalciferol) drops (4000 IU) once daily for three months. One arm received only vitamin D (VD arm), while the second arm received vitamin D along with PA (VDPA arm).. Of the 1,235 CKD stage 2-4 subjects contacted, forty-six subjects were enrolled. Eighteen were assigned to VD arm and twenty-eight were assigned to VDPA arm. Between groups comparison shows that bicep strength increases from 15 to 17 kg. Likewise, back flexibility and aerobic fitness also increased among those who receive vitamin D and physical activity, however these differences were not statistically significant (p>0.05). Sensitivity analysis within group comparison shows rise of bicep strength from 13.8 kg to 15.2 kg in the VD alone arm (p=0.05); however, in the VDPA arm, there is a greater difference of 14.3 kg to 17.2 kg (p<0.001).. Targeted PA among CKD patients has potential to improve bicep strength and back flexibility. However, as the sample size was small, further studies would be required to suggest whether a PA should be included as part of the treatment regimen.

Topics: Cholecalciferol; Exercise; Humans; Muscle Strength; Pakistan; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Decreased serum concentrations of 25-hydroxyvitamin D (25(OH)D) affect people with chronic kidney disease (CKD); lower concentrations of 25(OH)D have been associated with decrease in nutritional status indicators. On the other hand, muscle resistance exercise has improved the nutritional status of patients with CKD.The aim of this study was to evaluate the effect of resistance exercise and dietary supplementation with cholecalciferol on nutritional status indicators in adults with stage 4 CKD.. Patients with an estimated glomerular filtration rate between 15 and 29 mL/min/1.73 m. Thirty-nine patients of a median age of 48 (36-52) years had an estimated glomerular filtration rate of 21.8 ± 6.5 mL/min/1.73 m. Supplementation with cholecalciferol improves serum concentrations of 25(OH)D and, when combined with resistance exercise, improved muscle function as measured by handgrip strength in a study of patients with CKD not on dialysis.

Topics: Adult; Cholecalciferol; Dietary Supplements; Female; Hand Strength; Humans; Male; Middle Aged; Nutritional Status; Renal Insufficiency, Chronic; Resistance Training; Vitamin D

Chronic kidney disease (CKD) is a common complication of type 2 diabetes that can lead to end-stage kidney disease and is associated with high cardiovascular risk. Few treatments are available to prevent CKD in type 2 diabetes.. To test whether supplementation with vitamin D3 or omega-3 fatty acids prevents development or progression of CKD in type 2 diabetes.. Randomized clinical trial with a 2 × 2 factorial design conducted among 1312 adults with type 2 diabetes recruited between November 2011 and March 2014 from all 50 US states as an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), coordinated by a single center in Massachusetts. Follow-up was completed in December 2017.. Participants were randomized to receive vitamin D3 (2000 IU/d) and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; 1 g/d) (n = 370), vitamin D3 and placebo (n = 333), placebo and omega-3 fatty acids (n = 289), or 2 placebos (n = 320) for 5 years.. The primary outcome was change in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) from baseline to year 5.. Among 1312 participants randomized (mean age, 67.6 years; 46% women; 31% of racial or ethnic minority), 934 (71%) completed the study. Baseline mean eGFR was 85.8 (SD, 22.1) mL/min/1.73 m2. Mean change in eGFR from baseline to year 5 was -12.3 (95% CI, -13.4 to -11.2) mL/min/1.73 m2 with vitamin D3 vs -13.1 (95% CI, -14.2 to -11.9) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.5] mL/min/1.73 m2). Mean change in eGFR was -12.2 (95% CI, -13.3 to -11.1) mL/min/1.73 m2 with omega-3 fatty acids vs -13.1 (95% CI, -14.2 to -12.0) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.6] mL/min/1.73 m2). There was no significant interaction between the 2 interventions. Kidney stones occurred among 58 participants (n = 32 receiving vitamin D3 and n = 26 receiving placebo) and gastrointestinal bleeding among 45 (n = 28 receiving omega-3 fatty acids and n = 17 receiving placebo).. Among adults with type 2 diabetes, supplementation with vitamin D3 or omega-3 fatty acids, compared with placebo, resulted in no significant difference in change in eGFR at 5 years. The findings do not support the use of vitamin D or omega-3 fatty acid supplementation for preserving kidney function in patients with type 2 diabetes.. ClinicalTrials.gov Identifier: NCT01684722.

Topics: Aged; Cholecalciferol; Diabetes Mellitus, Type 2; Disease Progression; Docosahexaenoic Acids; Double-Blind Method; Drug Therapy, Combination; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Gastrointestinal Hemorrhage; Glomerular Filtration Rate; Humans; Kidney; Kidney Calculi; Male; Medication Adherence; Middle Aged; Placebos; Renal Insufficiency, Chronic; Time Factors; United States; Vitamins

The role of vitamin D supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD) is controversial. The objective of this study was to evaluate the effects of long-term cholecalciferol supplementation on VC in nondialysis patients with CKD stages 3-4 with hypovitaminosis D.. During the study, VC did not change in the treated insufficient group (418 [81-611] to 364 [232-817] AU, P = 0.25) but increased in the placebo group (118 [37-421] to 199 [49-490] AU, P = 0.01). The calcium score change was inversely correlated with 25(OH)D change (r = -0.45; P = 0.037) in the treated insufficient group but not in the placebo group. Renal function did not change in the insufficient, treated, and placebo groups. In multivariate analysis, there was no difference in VC progression between the treated and placebo insufficient groups (interaction P = 0.92). In the deficient group, VC progressed (265 [84-733] to 333 [157-745] AU; P = 0.006) and renal function declined (33 [26-43] to 23 [17-49] mL/min/1.73 m. Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cholecalciferol; Dietary Supplements; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial.. Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6.. Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels.. Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Topics: Adult; Aged; Biomarkers; Carotid Intima-Media Thickness; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Interleukin-6; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Parathyroid Hormone; Peritoneal Dialysis; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Calcidiol insufficiency may accelerate the development of secondary hyperparathyroidism (SHPT). We tested the effect of a substantial increase in calcidiol on mineral metabolism in patients with chronic kidney disease (CKD).. Ninety-five patients with CKD Stages 3-4, parathyroid hormone (PTH) above 6.8 pmol/L and calcidiol below 75 nmol/L were randomized to receive either cholecalciferol 8000 IU/day or placebo for 12 weeks. The primary endpoint was difference in the mean change in iPTH after 12 weeks. The proportion of participants having a 30% reduction in PTH and the effect on hand grip strength, fatigue and different biochemical variables were also investigated.. Baseline calcidiol was 57.5 ± 22 and 56.8 ± 22 nmol/L in the cholecalciferol and placebo groups, respectively. The corresponding concentrations of PTH were 10.9 ± 5 and 13.1 ± 9 pmol/L. Calcidiol increased to 162 ± 49 nmol/L in patients receiving cholecalciferol, and PTH levels remained constant at 10.5 ± 5 pmol/L. In the placebo group, calcidiol remained stable and PTH increased to 15.2 ± 11 pmol/L. The mean change in PTH differed significantly between the two groups (P < 0.01). The proportion of subjects reaching a 30% decrease in PTH did not differ. No effect on grip strength, fatigue, phosphate or fibroblast growth factor 23 was observed. Cholecalciferol treatment resulted in stable calcium concentrations and a substantial increase in calcitriol.. Treatment with high daily doses of cholecalciferol in patients with CKD Stages 3-4 halts the progression of SHPT and does not cause hypercalcaemia or other side effects.

Topics: Aged; Calcium; Calcium-Regulating Hormones and Agents; Cholecalciferol; Disease Progression; Double-Blind Method; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Prognosis; Renal Insufficiency, Chronic

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100-3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH)

Topics: Biomarkers; Cardiovascular Diseases; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Pulse Wave Analysis; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins

Topics: Adult; Aged; Biomarkers; Bone Diseases, Metabolic; Calcitriol; Cholecalciferol; Dietary Supplements; Female; Humans; Male; Middle Aged; Minerals; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D

Adults with diabetes (DM) and chronic kidney disease (CKD) are at risk for vitamin D (vitD) insufficiency, suboptimal bone health and reduced quality of life (QoL) due to limited sunlight exposure, poor vitD intake and CKD.. This open-labeled, randomized clinical trial, compared the impact of daily (2000 IU/D) verses monthly (40,000 IU/month) vitD. Participants (18-80 years) were randomized to daily (n = 60) or monthly (n = 60) vitD. Daily (2000 IU/D) and monthly (40,000 IU/month) vitD

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Body Mass Index; Bone and Bones; Bone Density; Cholecalciferol; Collagen Type I; Diabetes Mellitus; Dietary Supplements; Dose-Response Relationship, Drug; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Male; Middle Aged; Osteocalcin; Patient Compliance; Peptides; Quality of Life; Renal Insufficiency, Chronic; Vitamin D Deficiency; Young Adult

Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production.. A randomized controlled trial of daily vitamin D supplementation for 12 weeks was performed with the aim to test the effects of 4000 versus 400 IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children's hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring.. These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or those on dialysis.

Topics: C-Reactive Protein; Child; Cholecalciferol; Cohort Studies; Dietary Supplements; Female; Glomerular Filtration Rate; Hepcidins; Humans; Male; Patient Compliance; Pilot Projects; Renal Insufficiency, Chronic; Vitamins

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; 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Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Patients with chronic kidney disease (CKD) demonstrate complex mineral metabolism derangements and a high prevalence of vitamin D deficiency. However, the optimal method of 25-hydroxyvitamin D (25(OH)D) repletion is unknown, and trials analysing the comparative efficacy of cholecalciferol and ergocalciferol in this population are lacking. We conducted a randomised clinical trial of cholecalciferol 1250μg (50 000 IU) weekly v. ergocalciferol 1250μg (50 000 IU) weekly for 12 weeks in forty-four non-dialysis-dependent patients with stage 3-5 CKD. The primary outcome was change in total 25(OH)D from baseline to week 12 (immediately after therapy). Secondary analyses included the change in 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone (PTH), D2 and D3 sub-fractions of 25(OH)D and 1,25(OH)2D and total 25(OH)D from baseline to week 18 (6 weeks after therapy). Cholecalciferol therapy yielded a greater change in total 25(OH)D (45·0 (sd 16·5) ng/ml) v. ergocalciferol (30·7 (sd 15·3) ng/ml) from baseline to week 12 (P<0·01); this observation partially resulted from a substantial reduction in the 25(OH)D3 sub-fraction with ergocalciferol. However, following cessation of therapy, no statistical difference was observed for total 25(OH)D change from baseline to week 18 between cholecalciferol and ergocalciferol groups (22·4 (sd 12·7) v. 17·6 (sd 8·9) ng/ml, respectively; P=0·17). We observed no significant difference between these therapies with regard to changes in serum PTH or 1,25(OH)2D. Therapy with cholecalciferol, compared with ergocalciferol, is more effective at raising serum 25(OH)D in non-dialysis-dependent CKD patients while active therapy is ongoing. However, levels of 25(OH)D declined substantially in both arms following cessation of therapy, suggesting the need for maintenance therapy to sustain levels.

Topics: 25-Hydroxyvitamin D 2; Academic Medical Centers; Adult; Aged; Calcifediol; Calcitriol; Cholecalciferol; Cohort Studies; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Follow-Up Studies; Humans; Kansas; Male; Middle Aged; Outpatient Clinics, Hospital; Parathyroid Hormone; Renal Insufficiency, Chronic; Reproducibility of Results; Vitamin D Deficiency

Growing evidence indicates that vitamin D receptor activation may have antiproteinuric effects. We aimed to evaluate whether vitamin D supplementation with daily cholecalciferol could reduce albuminuria in proteinuric chronic kidney disease (CKD) patients.. This 6-month prospective, controlled, intervention study enrolled 101 non-dialysis CKD patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666 IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of their vitamin D status, did not receive any cholecalciferol, and were considered as the control group.. Cholecalciferol administration led to a rise in mean 25(OH)D levels by 53.0 ± 41.6% (P < 0.001). Urinary albumin-to-creatinine ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284 (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol group, and there was no change in the control group. Reduction in a uACR was observed in the absence of significant changes in other factors, which could affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive treatment. Six-month changes in 25(OH)D levels were significantly and inversely associated with that in the uACR (Pearson's R = -0.519; P = 0.036), after adjustment by age, sex, body mass index, BP, glomerular filtration rate and antiproteinuric treatment. The mean PTH decreased by -13.8 ± 20.3% (P = 0.039) only in treated patients, with a mild rise in phosphate and calcium-phosphate product [7.0 ± 14.7% (P = 0.002) and 7.2 ± 15.2% (P = 0.003), respectively].. In addition to improving hyperparathyroidism, vitamin D supplementation with daily cholecalciferol had a beneficial effect in decreasing albuminuria with potential effects on delaying the progression of CKD.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Albuminuria; Cholecalciferol; Dietary Supplements; Disease Progression; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Hormone; Phosphates; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Patients on chronic dialysis are at increased risk of vitamin D deficiency. In observational studies plasma 25-hydroxyvitamin D (p-25(OH) D) levels are inversely correlated with plasma BNP and adverse cardiovascular outcomes. Whether a causal relation exists has yet to be established. The aim of this study was to test the hypothesis that cholecalciferol supplementation improves cardiac function and reduces blood pressure (BP) and pulse wave velocity (PWV) in patients on chronic dialysis.. In a randomized, placebo-controlled, double-blind study, we investigated the effect of 75 μg (3000 IU) cholecalciferol daily for 6 months, in patients on chronic dialysis. We performed two-dimensional echocardiography, with doppler and tissue-doppler imaging, 24-h ambulatory BP (24-h BP), PWV, augmentation index (AIx), central BP (cBP) and brain natriuretic peptide (BNP) measurements at baseline and after 6 months.. Sixty-four patients were allocated to the study. Fifty dialysis patients with a mean age of 68 years (range: 46-88) and baseline p-25(OH) D of 28 (20;53) nmol/l completed the trial. Cholecalciferol increased left ventricular (LV) volume, but had no impact on other parameters regarding LV structure or left atrial structure. LV systolic function, LV diastolic function, PWV, cBP, AIx and BNP were not changed in placebo or cholecalciferol group at follow-up. 24-h BP decreased significantly in placebo group and tended to decrease in cholecalciferol group without any difference between treatments.. Six months of cholecalciferol treatment in patients on chronic dialysis did not improve 24-h BP, arterial stiffness or cardiac function.. NCT01312714, Registration Date: March 9, 2011.

Topics: Aged; Blood Pressure; Cholecalciferol; Double-Blind Method; Female; Heart; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Placebo Effect; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin K Deficiency; Vitamins

The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 (25[OH]D) levels<30ng/mL in patients treated with maintenance hemodialysis, but does not provide a specific treatment protocol.. 2-center, double-blind, randomized, 13-week, controlled trial followed by a 26-week open-label study.. 55 adult maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from June 2008 through October 2009.. Cholecalciferol, 25,000IU, per week orally versus placebo for 13 weeks, then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines.. Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks. Secondary outcomes included the percentage of patients with normal calcium, phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures included incidence of hypercalcemia and hypervitaminosis D.. Blood calcium and phosphate were measured weekly; iPTH, 25(OH)D, 1,25-dihydroxyvitamin D3 (1,25[OH]2D), and bone turnover markers, trimonthly; fetuin A and fibroblast growth factor 23 (FGF-23) serum levels and aortic calcification scores were determined at weeks 0 and 39.. The primary end point significantly increased in the treatment group compared with the placebo group (61.5% vs 7.4%; P<0.001), as well as 1,25(OH)2D levels (22.5 [IQR, 15-26] vs 11 [IQR, 10-15]pg/mL; P<0.001) and the proportion of patients achieving the target calcium level (76.9% vs 48.2%; P=0.03). Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups. The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group.. Small size of the study population.. Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients. Further evaluation of clinical end points is suggested.

Topics: Aged; Cholecalciferol; Double-Blind Method; Female; Fibroblast Growth Factor-23; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D

Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D(3) supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca(2+)](i)) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D(3) supplementation of CKD patients resulted in the decrease of [Ca(2+)](i) (119.79+/-5.87 nmol/l vs. 105.36+/-3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75+/-22.89 nmol P(i)/mg/h) remained unchanged after vitamin D(3) supplementation (40.96+/-17.74 nmol P(i)/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D(3), was reduced by 34 % (42.01+/-20.64 nmol P(i)/mg/h) in comparison to healthy volunteers (63.68+/-20.32 nmol P(i)/mg/h, n=28, P<0.001). These results indicate that vitamin D(3) supplementation had a lowering effect on [Ca(2+)](i) and negligible effect on PMCA activity in CKD patients.

Topics: Adult; Aged; Calcium; Case-Control Studies; Cholecalciferol; Dietary Supplements; Healthy Volunteers; Humans; Middle Aged; Plasma Membrane Calcium-Transporting ATPases; Renal Insufficiency, Chronic; Vitamin D Deficiency

Recent understanding of extrarenal production of calcitriol has led to the use of more vitamin D supplementation in CKD populations. This paper reports the effect of cholecalciferol supplementation on calcium absorption.. Paired calcium absorption tests were done before and after 12-13 weeks of 20,000 IU weekly cholecalciferol supplementation in 30 participants with stage 5 CKD on hemodialysis. The study was conducted from April to December of 2011. Calcium absorption was tested with a standardized meal containing 300 mg calcium carbonate intrinsically labeled with (45)Ca; 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured.. 25-Hydroxyvitamin D rose from 14.2 ng/ml (11.5-18.5) at baseline to 49.3 ng/ml (42.3-58.1) at the end of the study (P<0.001). 1,25-Dihydroxyvitamin D rose from 15.1 (10.5-18.8) pg/ml at baseline to 20.5 (17.0-24.7) pg/ml at the end of the study (P<0.001). The median baseline calcium absorption was 12% (7%-17%) and 12% (7%-16%) at the end of study.. Patients with stage 5 CKD on hemodialysis had very low calcium absorption values at baseline, and cholecalciferol supplementation that raised 25(OH)D levels to 50 ng/ml had no effect on calcium absorption.

Topics: Aged; Calcium Carbonate; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Female; Humans; Intestinal Absorption; Male; Middle Aged; Nebraska; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors; Treatment Outcome; Vitamin D; Vitamins

To assess the impact of vitamin D supplementation (cholecalciferol) on the insulin sensitivity and metabolic health of patients with chronic kidney disease (CKD).. Twenty-eight adult patients with CKD stages 3-4 were recruited from the outpatient department of the Princess Alexandra Hospital (Brisbane, Australia) to a double-blind randomized trial of cholecalciferol (vitamin D3) 2000 IU/day or placebo for 6 months. Metabolic parameters at baseline were compared with 20 non-CKD adults. The primary outcome was an improvement in insulin resistance (glucose disposal rate, GDR) at 6 months (quantified by hyperinsulinaemic euglycaemic clamp). Carbohydrate and lipid oxidation rates were assessed by indirect calorimetry.. At baseline, patients were significantly insulin-resistant compared with lean younger non-CKD individuals (n = 9; GDR 3.42 vs. 5.76 mg/kg per minute, P = 0.001), but comparable with their age-, gender- and weight-matched non-CKD counterparts (n = 11; 3.42 vs. 3.98 mg/kg per minute, P = 0.4). 25-Hydroxyvitamin D did not change in the placebo group, but rose from 95 ± 37 to 146 ± 25 nmol/L with treatment (P = 0.0001). Post treatment, there was no difference in GDR between groups (GDR 3.38 vs. 3.52 mg/kg per minute, ancova P = 0.4). There was a relative increase in hyperinsulinaemic oxidative disposal of glucose with treatment (within-group P = 0.03).. Supplementation with cholecalciferol in CKD 3-4 results in appreciable increases in 25-hydroxyvitamin D concentrations, but does not increase insulin sensitivity. The insulin resistance observed was similar among age-, sex- and body mass index-matched individuals with and without CKD. Whether renal dysfunction per se has any influence on the insulin sensitivity of an individual should be the subject of future work.

Topics: Aged; Cholecalciferol; Double-Blind Method; Female; Humans; Insulin Resistance; Male; Metabolic Diseases; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Failure; Vitamins

We aimed to investigate the effect of single, high-dose intramuscular cholecalciferol on vitamin D3 and intact parathyroid hormone (iPTH) levels in children with chronic kidney disease (CKD).. Between January 2012 and June 2012, we conducted a prospective, uncontrolled study at the Pediatric Nephrology Unit of King Abdulaziz University Hospital, Jeddah, to investigate the effect of single, high-dose intramuscular vitamin D3 on 25(OH)D3 and iPTH levels in vitamin D insufficient/deficient children with CKD. Serum vitamin D3, iPTH, calcium, phosphate, alkaline phosphatase (ALP), and creatinine levels were measured before intramuscular vitamin D3 (300,000 IU) administration, and these were subsequently repeated at 1 and 3 months after treatment. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA).. Nineteen children fulfilled the criteria. At 3 months after treatment, vitamin D3 levels were significantly higher than at baseline (p < 0.001) but lower than the levels at 1 month. iPTH levels decreased significantly at 3 months (p = 0.01); however, the drop in iPTH levels was not significant at 1 month (p = 0.447). There were no changes in calcium, phosphate, ALP, or creatinine levels after treatment.. Single-dose intramuscular vitamin D3 (300,000 IU) resulted in significant improvement of vitamin D3 and iPTH levels in children with CKD.

Topics: Adolescent; Child; Child, Preschool; Cholecalciferol; Creatinine; Female; Humans; Male; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic

Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity.. In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa.. By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells.. High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Chemokine CCL2; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Immunity; Inflammation; Interferon-gamma; Interleukin-6; Male; Middle Aged; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha; Vitamin D

Vitamin D deficiency is highly prevalent among hemodialysis patients, but little data exist in support of an optimal repletion regimen.. The objective was to ascertain the efficacy of weekly very-high-dose cholecalciferol (vitamin D(3)) in correcting vitamin D insufficiency and deficiency in patients with stage 5D chronic kidney disease.. We conducted a prospective, double-blind, randomized controlled pilot study that compared placebo with very high doses of oral cholecalciferol for 3 wk (200,000 IU/wk) in hemodialysis patients. We examined the rate of correction of vitamin D insufficiency or deficiency and the effect of treatment on markers of mineral metabolism and routine laboratory variables.. Twenty-seven subjects received placebo, and 25 received cholecalciferol. The majority (94%) of subjects had serum 25-hydroxyvitamin D [25(OH)D] concentrations <30 ng/mL. Study groups were similar with respect to baseline clinical characteristics, with the exception of hemoglobin concentrations, which were lower in the cholecalciferol-treated group (P < 0.04). At follow-up, 90.5% of subjects treated with cholecalciferol achieved serum 25(OH)D concentrations ≥30 ng/mL in contrast to 13.6% of the placebo group. There were no significant changes in serum calcium, phosphate, or intact parathyroid hormone during the study.. Short-term, high-dose oral cholecalciferol treatment of vitamin D deficiency in hemodialysis patients appears to be effective and with no evidence of toxic effects. This trial was registered at clinicaltrials.gov as NCT00912782.

Topics: Adult; Aged; Cholecalciferol; Double-Blind Method; Drug Administration Schedule; Female; Hemoglobins; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Hypovitaminosis D is common in chronic kidney disease (CKD). Effects of 25-hydroxyvitamin D replenishment in CKD are not well described.. An 8-week randomized, placebo-controlled, double-blind parallel intervention study was conducted in haemodialysis (HD) and non-HD CKD patients. Treatment consisted of 40,000 IU of cholecalciferol orally per week. Plasma 25-hydroxyvitamin D (25-OHD), plasma 1,25-dihydroxyvitamin D (1,25-diOHD), plasma parathyroid hormone (PTH), serum phosphate, ionized serum calcium and serum fibroblast growth factor 23 (FGF-23) were analysed. We also investigated biomarkers related to cardiovascular disease (plasma D-dimer, plasma fibrinogen, plasma von Willebrand factor antigen and activity, plasma interleukin 6, plasma C-reactive protein, blood pressure, aortic augmentation index, aortic pulse wave velocity and 24-h urinary protein loss). Objective and subjective health variables were assessed (muscle function tests, visual analogue scores and Health Assessment Questionnaire).. Fifty-two CKD patients with 25-OHD <50 nmol/L at screening were included. Cholecalciferol supplementation led to a significant increase to a median of 155 nmol/L 25-OHD (interquartile range 137-173 nmol/L) in treated patients (n = 25, P < 0.001). In non-HD patients, we saw a significant increase in 1,25-diOHD (n = 13, P < 0.01) and a lowering of PTH (n = 13, P < 0.001). This was not observed in HD patients. Cholecalciferol supplementation caused a significant increase in serum calcium and FGF-23.. 25-OHD replenishment was effectively obtained with the employed cholecalciferol dosing. In non-HD patients, it had favourable effects on 1,25-diOHD and PTH. Vitamin D-supplemented patients must be monitored for hypercalcaemia. The present study could not identify significant pleiotropic effects of 25-OHD replenishment.

Topics: Aged; Biomarkers; Calcification, Physiologic; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Fibroblast Growth Factor-23; Glomerular Filtration Rate; Humans; Male; Middle Aged; Muscles; Prognosis; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins

Vitamin D deficiency contributes to secondary hyperparathyroidism, which occurs early in chronic kidney disease (CKD).. We aimed to determine whether high-dose cholecalciferol supplementation for 1 y in early CKD is sufficient to maintain optimal vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] concentration ≥30 ng/mL) and decrease serum parathyroid hormone (PTH). A secondary aim was to determine the effect of cholecalciferol on blood pressure and serum fibroblast growth factor-23 (FGF23).. This was a double-blind, randomized, placebo-controlled trial. Forty-six subjects with early CKD (stages 2-3) were supplemented with oral cholecalciferol (vitamin D group; 50,000 IU/wk for 12 wk followed by 50,000 IU every other week for 40 wk) or a matching placebo for 1 y.. By 12 wk, serum 25(OH)D increased in the vitamin D group only [baseline (mean ± SD): 26.7 ± 6.8 to 42.8 ± 16.9 ng/mL; P < 0.05] and remained elevated at 1 y (group-by-time interaction: P < 0.001). PTH decreased from baseline only in the vitamin D group (baseline: 89.1 ± 49.3 to 70.1 ± 24.8 pg/mL; P = 0.01) at 12 wk, but values were not significantly different from baseline at 1 y (75.4 ± 29.5 pg/mL; P = 0.16; group-by-time interaction: P = 0.09). Group differences were more pronounced in participants with secondary hyperparathyroidism (group-by-time interaction: P = 0.004). Blood pressure and FGF23 did not change in either group.. After 1 y, this oral cholecalciferol regimen was safe and sufficient to maintain serum 25(OH)D concentrations and prevent vitamin D insufficiency in early CKD. Furthermore, serum PTH improved after cholecalciferol treatment, particularly in patients who had secondary hyperparathyroidism.

Topics: Aged; Calcifediol; Cholecalciferol; Diet; Dietary Supplements; Double-Blind Method; Female; Fibroblast Growth Factor-23; Georgia; Hospitals, Veterans; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Intention to Treat Analysis; Male; Middle Aged; Parathyroid Hormone; Pilot Projects; Prevalence; Renal Insufficiency, Chronic; Severity of Illness Index; Vitamin D Deficiency

We aimed to determine the effect of a monthly oral vitamin D on the serum 25-hydroxyvitamin D levels and iPTH levels in patients with CKD.. This was a prospective controlled trial of 48 patients with CKD stage 3-4. Patients were divided into two groups Group1 the cholecalciferol treatment group, Group 2, the control group. One patient in Group 1, and 3 patients in Group2 were excluded after the baseline 25(OH)D levels were determined to be greater than 30ng/ml. Two patients in Group1, and one patient in Group 2 were excluded after the baseline iPTH was determined to be less than 70 pg/ml and greater than 300 pg/ml. Five patients in both groups were lost to follow-up. Thus, a total of 16 patients in Group 1 and 15 patients in Group2 completed the three month study. Group1 patients received 300,000 IU month oral cholecalciferol.. The mean serum 25(OH)D concentration of the group1 was significantly higher at baseline (P=0.039). At the end of the three months; serum 25 (OH) D level increased significantly in Group1 (P=0.001). iPTH level of Group1 was significantly lower at baseline (P=0.034). The values of the group1 before and end of third month was compared, serum Ca (P=0.011), P (P=0.013) level showed significant increase, but no significant increase in the Group 2 (P>0.05). The groups had not a clinically significant change in serum Ca and P level (P>0.05).. Oral cholecalciferol supplementation can be used safely and effective in reducing iPTH levels and correcting vitamin D insufficiency/deficiency in patients with CKD.

Topics: Administration, Oral; Adult; Aged; Bone Density Conservation Agents; Cholecalciferol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Follow-Up Studies; Glomerulonephritis; Humans; Hyperparathyroidism; Hypertension; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome; Vitamin D

Denosumab can improve bone health in advanced kidney disease (CKD) but is associated with hypocalcemia. We created a clinical care pathway focused on the safe provision of denosumab in advanced CKD that reduced the risk of hypocalcemia by 37% at our hospital. Similar pathways could be adopted and tested in other centers.. There is an increased risk of hypocalcemia with denosumab in advanced chronic kidney disease (CKD). We aimed to reduce the proportion of patients with advanced CKD who experienced denosumab-induced hypocalcemia at our center.. There were 6 patients with advanced CKD treated with denosumab prior to the implementation of our care pathway (March 2015-October 2020; 83% receiving dialysis). At the time of their denosumab injection, 83% were using 500-1000 mg of calcium, and 83% used 1000-2000 IU of vitamin D. A clinical care pathway focused on the safe provision of denosumab in advanced CKD reduced the risk of hypocalcemia in patients treated in our hospital. Similar pathways could be adopted and tested in other centers.

Topics: Bone Density Conservation Agents; Calcium; Cholecalciferol; Denosumab; Humans; Hypercalcemia; Hyperphosphatemia; Hypocalcemia; Quality Improvement; Renal Insufficiency, Chronic

Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism.. This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml.. Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol.. Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Calcium; Cholecalciferol; Female; Furosemide; Humans; Hyperparathyroidism, Secondary; Hyperuricemia; Male; Middle Aged; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Retrospective Studies; Uric Acid; Vitamin D; Vitamin D Deficiency

Abnormalities related to mineral and bone metabolism are a common finding in chronic kidney disease (CKD). Vitamin D compounds are often prescribed to CKD patients with the purpose to control secondary hyperparathyroidism and reduce the risk of high-turnover bone disease. However, data on the effect of vitamin D sterols on bone histology in non-dialysis CKD is limited.. A prospective controlled study was conducted on a cohort of 56 patients with CKD stages 3 and 4. 19 patients on calcitriol and 12 patients on cholecalciferol were compared to a group of 25 age- and sex-matched controls. Participants underwent a tetracycline double-labelled transiliac bone biopsy before starting therapy and again 12 months later. Changes from baseline in circulating biomarkers and bone histomorphometric parameters were analyzed.. Low-turnover bone disease was the most common pattern of renal osteodystrophy on the initial biopsy. There was no difference in biochemical or histomorphometric values between the three study groups at baseline. Serum intact parathormone (iPTH) and bone formation rate decreased significantly in calcitriol-treated patients, with prevalence of low-turnover bone disease doubling from baseline. In contrast, no significant changes were noted in cholecalciferol-treated and control subjects.. Calcitriol was effective in preventing secondary hyperparathyroidism and high-turnover bone disease. However, it was associated with an increased risk of developing or aggravating low-turnover bone disease. In the absence of a bone biopsy, calcitriol use in pre-dialysis CKD should be reserved for patients with a progressive rise in iPTH levels, in whom high-turnover bone disease is suspected.

Topics: Calcitriol; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dialysis; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Sterols; Vitamin D; Vitamins

Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol).. Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo.. More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3-7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 μg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 μg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment.. Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.

Topics: Calcifediol; Cholecalciferol; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Overweight; Parathyroid Hormone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

The 25-hydroxyvitamin D3 (25OHD3) deficiency in chronic kidney disease (CKD) is associated with immune system dysfunction (pro-inflammatory cytokines storm) through macrophages renal infiltration, oxidative stress (OxS) damage and athero-thromboembolic risk. Conversely, cholecalciferol supplementation (25OHD-S) prevents kidney fibrosis by inhibition of vascular calcification and nephrotic apoptosis (nephrons reduction). The objective of this study was to investigate the pleiotropic effects of 25OHD-S on immunomodulation, antioxidant status and in protecting against thromboembolic events in deficiency CKD Black and White individuals living in the Southern Sahara (SS). The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/day/24 weeks in Black (n = 156) and White (n = 150). Total serum vitamin D was determined by liquid chromatography-tandem mass spectrometry. All biomarkers of pro-inflammatory cytokines (PIC) were assessed by ELISA tests. OxS markers were assessed by Randox kits. Homocysteine and lipoproteine (a) were evaluated by biochemical methods as biomarkers of atherothromboembolic risk. All statistical analyses were performed with Student’s t-test and one-way ANOVA. The Pearson test was used to calculate the correlation coefficient. The means will be significantly different at a level of p value < 0.05. Multiple logistic regressions were performed using Epi-info and Statview software. Vitamin D deficiency alters the PIC profile, OxS damage and atherothrombogenic biomarkers in both SS groups in the same manner; however, these disorders are more acute in Black compared to White SS individuals. The results showed that the serum 25OHD3 concentrations became normal (>75 nmol/L or >30 ng/mL) in the two groups. We have shown that the dose and duration of 25OHD-S treatment are not similar in Black SS residents compared to White SS subjects, whilst the same inhabit the south Sahara environment. It appears that a high dose intermittent over a long period (D60: 36 weeks) was more efficient in Black people; while a lower dose for a short time is sufficient (D2: 24 weeks) in their White counterparts. The oral 25OHD-S attenuates PIC overproduction and OxS damage, but does not reduce athero-thromboembolic risk, particularly in Black SS residents.

Topics: Cholecalciferol; Cytokine Release Syndrome; Cytokines; Dietary Supplements; Humans; Oxidative Stress; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

To see the efficacy of oral cholecalciferol administered to chronic kidney disease patients with vitamin D deficiency.. The prospective interventional study was conducted at the Indus Hospital, Karachi, from January 11, 2017, to January 10, 2018, and comprised diagnosed pre-dialysis chronic kidney disease patients of either gender aged >14 years having vitamin D deficiency. Oral vitamin D 50,000IU was given weekly to those who had severe deficiency <10ng/ml, and every other week to those with less severe 10-25ng/ml deficiency for 3 months. Improvement in vitamin D level was checked along with other chronic kidney disease markers every month over the 3-month period. Data was analysed using SPSS 24.. Of the 186 patients enrolled, 129(%) completed the study; 76(58.5%) males and 53(40.8%) females. Overall, 105(81.4%) patients achieved normal vitamin D levels after 3 months of treatment. Significant negative but weak correlation of phosphate, creatinine and intact parathyroid hormone levels was found with vitamin D (p<0.05). Significant positive but weak correlation was found between albumin and vitamin D levels (p<0.05).. Significant efficacy of oral vitamin D in chronic kidney disease patients was seen.

Topics: Cholecalciferol; Female; Humans; Male; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Data on the effect of vitamin D supplementation on fibroblast growth factor 23 (FGF23), in chronic kidney disease (CKD) are scarce. In a prospective interventional study, the effect of vitamin D supplementation on cFGF23 (C-terminal FGF23) levels in children with CKD stages 2-4 was examined. Forty-one children with CKD and vitamin D insufficiency were administered 600,000 units of cholecalciferol over 3 d; 88% of patients achieved sufficiency at 8 wk. Significant increase in serum cFGF23 and phosphate levels was observed in CKD stage 2 after supplementation, but not in CKD stages 3 and 4. There was no correlation of the change in cFGF23 level with baseline or change in bone health parameters (calcium, phosphate, parathormone or alkaline phosphatase) or with change in flow-mediated dilatation (FMD) of the brachial artery. It is concluded that cholecalciferol supplementation increases serum calcium and reduces PTH, but does not adversely affect FGF23 levels in CKD.

Topics: Alkaline Phosphatase; Calcium; Child; Cholecalciferol; Dietary Supplements; Fibroblast Growth Factors; Humans; Parathyroid Hormone; Phosphates; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

The regulation of vitamin D

Topics: Cholecalciferol; Cytochrome P-450 Enzyme System; HEK293 Cells; Humans; Oximes; Receptors, Calcitriol; Renal Insufficiency, Chronic; Vitamin D; Vitamin D3 24-Hydroxylase

Several studies have shown that cholecalciferol supplementation (25OHD-S) in chronic kidney disease (CKD) improves kidney injury by reducing fibrosis-related vascular calcification and declining apoptosis-linked nephron damage.. Vitamin D deficiency alters in the same manner CMet, CRenal, and others biomarkers in both groups SS; however, these disorders are more acute in blacks compared to whites SS. Oral 25OHD-S a highlighted improvement of eGFR drop, SHPT decrease, decline proteinuria, and cardiac failure risk (NT-proBNP and cTnT) attenuation. Concomitantly, 25OHD-S normalizes

Topics: Biomarkers; Cardio-Renal Syndrome; Cholecalciferol; Dietary Supplements; Humans; Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic; Troponin T; Vitamin D Deficiency

To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population.. All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression.. Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001).. In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.

Topics: Aged; Aged, 80 and over; Calcifediol; Cholecalciferol; Cohort Studies; Comorbidity; COVID-19; COVID-19 Drug Treatment; Dietary Supplements; Female; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; SARS-CoV-2; Severity of Illness Index; Spain; Vitamin D; Vitamin D Deficiency

The rationale for the prescription of vitamin D analogues in patients with chronic kidney disease (CKD) is still a matter of debate. We aimed to compare native vs. active forms of vitamin D on pre-dialysis children with CKD and evaluate effects on calcium (Ca), phosphorus (P), and parathyroid hormone (PTH).. Thirty children with pre-dialysis CKD were enrolled in a prospective cross-over study. Patients were randomly classified into two groups. Group A received native cholecalciferol while group B received alfacalcidol for 3 months. After 1 month (washout period), patients were switched to receive the opposite form for another 3 months. Serum Ca, P, alkaline phosphatase (ALP), PTH, and 25(OH)D. Alfacalcidol and native vitamin D3 were equally effective in decreasing PTH levels and increasing serum 25(OH)D

Topics: Calcium; Child; Cholecalciferol; Cross-Over Studies; Humans; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D

In the present study, we aimed to investigate the relationship between serum vitamin D3 concentration and anaemia in patients with chronic kidney disease (CKD) in China, to assist understanding of the effects of vitamin D treatment in such patients.. A total of 225 patients with CKD were enrolled and a range of laboratory parameters were measured. The participants were allocated to three groups, according to their serum 25-hydroxyvitamin D3 concentration: a severe deficiency group, a deficiency group, and a sufficiency group. The prevalences of anaemia in the three groups were assessed, and the factors associated with anaemia in patients with CKD were analysed using logistic regression.. The prevalences of anaemia were 79.5% in the severe deficiency group, 63.5% in the deficiency group, and 48.0% in the sufficiency group. The prevalence of anaemia gradually increased with the severity of vitamin D3 deficiency. The prevalences of anaemia in participants with stages 1 to 5 CKD were 21.1%, 30.4%, 39.5%, 78.7%, and 94.6%, respectively.. Vitamin D3 deficiency may increase the risk of anaemia in patients with CKD.

Topics: Anemia; China; Cholecalciferol; Cross-Sectional Studies; Humans; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is frequent in pediatric nephrology. The 2017 European guidelines recommend keeping 25OH vitamin D (25-D) levels within the 75-120 nmol/L range, ideally with daily supplementation. Intermittent supplementation with D3 has also been proposed. We aimed to assess the influence of our local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months. VITATOL is a prospective single-center study performed in our tertiary unit in children and teenagers followed for chronic kidney disease (CKD), kidney transplantation, or stable chronic nephrotic syndrome with 25-D levels below 75 nmol/L. Intermittent oral cholecalciferol (100,000 IU) was administered depending on baseline vitamin D levels and body weight. The primary outcome was the change in 25-D levels between baseline and 2 months. Secondary outcomes were the evolution of the main mineral biomarkers. Thirty-seven patients were included. Two months after beginning supplementation, corresponding to a median(min-max) of 46 (14-79) days after the last dose of vitamin D, 25-D levels increased from 50 to 76 nmol/L (p < 0.001), 18 patients having 25-D levels within the target range and 2 above. All patients displayed 25-D levels above 50 nmol/L. There were no significant changes in phosphate, PTH, alkaline phosphatase, and FGF23 levels before and after supplementation. Calcium levels increased from 2.39 to 2.44 mmol/L (p = 0.017), but no differences in calciuria and urinary calcium/creatinine ratio were observed.Conclusion: This vitamin D supplementation protocol using intermittent moderate doses of cholecalciferol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria. What is Known: • Vitamin D deficiency is frequent in pediatric nephrology. • The 2017 European guidelines recommend keeping 25OH vitamin D levels within the 75-120 nmol/L range ideally with daily supplementation, but intermittent supplementation with D3 has also been proposed. What is New: • We assessed the influence of a local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months in children and teenagers followed in pediatric nephrology. • The intermittent cholecalciferol supplementation protocol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria.

Topics: Administration, Oral; Adolescent; Calcium-Regulating Hormones and Agents; Child; Cholecalciferol; Female; Fibroblast Growth Factor-23; Humans; Male; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Kidney transplant (KTx) recipients frequently have deficient or insufficient levels of serum vitamin D. Few studies have investigated the effect of cholecalciferol in these patients. We evaluated the efficacy of weekly cholecalciferol administration on parathyroid hormone (PTH) levels in stable KTx patients with chronic kidney disease stage 1-3.. In this retrospective cohort study, 48 stable KTx recipients (37 males, 11 females, aged 52 ± 11 years and 26 months post-transplantation) were treated weekly with oral cholecalciferol (7500-8750 IU) for 12 months and compared to 44 untreated age- and gender-matched recipients. Changes in levels of PTH, 25(OH) vitamin D (25[OH]D), serum calcium, phosphate, creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline, 6 and 12 months.. At baseline, clinical characteristics were similar between treated and untreated patients. Considering the entire cohort, 87 (94.6%) were deficient in vitamin D and 64 (69.6%) had PTH ≥130 pg/mL. Serum calcium, phosphate, creatinine and eGFR did not differ between groups over the follow-up period. However, 25(OH)D levels were significantly higher at both 6 (63.5 vs. 30.3 nmol/L, p < 0.001) and 12 months (69.4 vs. 30 nmol/L, p < 0.001) in treated vs. untreated patients, corresponding with a significant reduction in PTH at both 6 (112 vs. 161 pg/mL) and 12 months (109 vs. 154 pg/mL) in treated vs. untreated patients, respectively (p < 0.001 for both).. Weekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.

Topics: Adult; Calcium; Calcium-Regulating Hormones and Agents; Cholecalciferol; Cohort Studies; Creatinine; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Retrospective Studies; Vitamin D

Topics: Calcimimetic Agents; Calcitriol; Chelating Agents; Cholecalciferol; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Phosphates; Phosphorus, Dietary; Polycystic Kidney, Autosomal Dominant; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

The purpose of this retrospective cohort study was to measure the difference between cholecalciferol and ergocalciferol in their ability to effect vitamin D, parathyroid hormone (PTH), calcium, and phosphorous serum concentrations in patients with stage 3 or 4 chronic kidney disease.. This was a retrospective cohort study conducted within a single-center ambulatory nephrology clinic. Patients eligible for the study were identified through medical records displaying each patient's initiation on either ergocalciferol or cholecalciferol from 2013 to 2016. Patients' baseline vitamin D, PTH, calcium, and phosphorous serum concentrations were taken prior to treatment initiation, and patients were reassessed with a second measurement within 12 months of therapy.. Out of 149 eligible patients, 110 were excluded. There were 33 patients included on cholecalciferol and 6 patients on ergocalciferol. A significant difference was observed in the percent change of phosphorous serum concentrations from baseline following drug administration (p=0.03). The mean changes from baseline to final serum phosphorous concentrations (mg/dL) were 0.12 and -0.3 for cholecalciferol and ergocalciferol, respectively. There was no significant difference in vitamin D (14.9, 15.1, p=0.97), PTH (5.6, 2.3, p=0.72), or calcium (0.05, -0.17, p=0.08) serum concentrations between cholecalciferol and ergocalciferol, respectively. There was a statistically significant increase in the mean change in serum phosphorous concentrations within the cholecalciferol group compared to the ergocalciferol group.. In this small pilot study, cholecalciferol treatment appeared to increase serum phosphorous concentrations compared to ergocalciferol. These observations may warrant further large-scale studies that are appropriately powered to validate such findings.

Topics: Adolescent; Adult; Aged; Calcium; Cholecalciferol; Cohort Studies; Ergocalciferols; Female; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Insufficiency, Chronic; Retrospective Studies; Vitamin D; Young Adult

While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D. The subjects given Vitamin D. We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012.

Topics: 24,25-Dihydroxyvitamin D 3; Aged; Cholecalciferol; Dietary Supplements; Ergocalciferols; Female; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients.. Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied.. There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (β = - 0.548, P < 0.001) and lower levels of 25(OH)D (β = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001).. Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

Topics: Adult; Aged; Brachial Artery; Cholecalciferol; Dietary Supplements; E-Selectin; Endothelium; Female; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Vascular Cell Adhesion Molecule-1; Vasodilation; Vitamin D; Vitamin D Deficiency; Vitamins

Chronic kidney disease (CKD) is a progressive condition characterized by irreversible loss of functional nephron mass due to variety of causes; an inevitable complication of CKD is metabolic bone disease, and this pathology is called as renal osteodystrophy (ROD). In this study, we aimed to determine the levels of serum sRANKL and intracellular NF-κB levels in peripheral blood osteoclast precursor cells in patients with stage 3 CKD.. Forty-one male patients aged 35-60 with CKD identified as stage 3 according to GFR calculated on the basis of creatinine values and 27 healthy male subjects with age ranging from 40 to 60 as control group were included in this study. Levels of biochemical parameters, vitamin D3, parathyroid hormone, bone mineral density, sRANKL and NF-κB were determined by using photometric, electrochemiluminescence, HPLC, ELISA and flow cytometric methods in control and patient groups, respectively.. When stage 3 CKD patients were compared with controls, patients with stage 3 CKD had statistically significantly higher iPTH levels, but they had statistically significantly lower vitamin D3 levels. However, the other biochemical parameters, bone mineral density, sRANKL and NF-κB levels did not reveal any significance.. In conclusion, vitamin D3 and iPTH levels seem to be important parameters for evaluating the early stages of ROD. The lack of statistically significant differences in the levels of sRANKL and NF-κB suggests that these parameters are not sufficient in the evaluation of bone metabolism in the early stages of renal failure.

Topics: Adult; Bone Density; Case-Control Studies; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Male; Middle Aged; NF-kappa B; Osteoclasts; Parathyroid Hormone; RANK Ligand; Renal Insufficiency, Chronic; Stem Cells

Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD).. Eight genetic variants in four genes (SHROOM3, MYH9, SLC7A9, and CST3) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls. Genetic variants were tested for association with the development of CKD (eGFR < 60 ml/min/1.73m. All eight variants were present in Saudi populations with minor allele frequency ranging from 16 to 46%. The risk variant in all four genes demonstrated the same direction of effect as observed in European populations. One variant, rs4821480, in MYH9 was significantly associated with increased risk of development of CKD (OR = 1.69, 95% CI 1.22-2.36, P = 0.002), but the additional variants were not statistically significant given our modest sample size.. CKD risk variants identified in European populations are present in Saudis. We did not find evidence to suggest heterogeneity of effect size compared to previously published estimates in European populations. Multivariable logistic regression analysis showed a statistically significant improvement in predicting the CKD using models with either FGF23 and vitamin D or FGF23, vitamin D level, and MYH9 genotypes (AUC = 0.93, 95% CI 0.90-0.95, P <  0.0001).

Topics: Adult; Aged; Alleles; Amino Acid Transport Systems, Basic; Case-Control Studies; Cholecalciferol; Cystatin C; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genotype; Glomerular Filtration Rate; Humans; Male; Microfilament Proteins; Middle Aged; Molecular Motor Proteins; Myosin Heavy Chains; Polymorphism, Single Nucleotide; Renal Insufficiency, Chronic; Risk Factors; Saudi Arabia

End-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. SNF472 was studied in three rat models: (1) prevention of vitamin D3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. Uremic rats presented lower plasma levels of SNF472 than control animals after i.v. infusion. CVC in non-uremic rats was inhibited by 60-70% after treatment with SNF472 and progression of cardiac calcification completely blocked. Development of CVC in uremic rats was inhibited by up to 80% following i.v. infusion of SNF472. SNF472 inhibits the development and progression of CVC in uremic and non-uremic rats in the same range of SNF472 plasma levels but using in each case the required dose to obtain those levels. These results collectively support the development of SNF472 as a novel therapeutic option for treatment of CVC in humans.

Topics: Animals; Calcinosis; Cardiovascular Diseases; Cholecalciferol; Disease Models, Animal; Disease Progression; Humans; Inositol; Kidney Failure, Chronic; Rats; Renal Insufficiency, Chronic; Uremia

Cardiovascular factors are an important cause of mortality in chronic kidney disease, and vitamin-D deficiency is common in this patient population. Therefore, we aimed to investigate the effect of oral cholecalciferol on cardiac mechanics in children with chronic kidney disease. A total of 41 children with chronic kidney disease - the patient group - and 24 healthy subjects - the control group - free of any underlying cardiac or renal disease with low 25-hydroxyvitamin-D3 levels were evaluated by conventional tissue Doppler imaging and two-dimensional speckle-tracking echocardiography, both at baseline and following Stoss vitamin-D supplementation. Left ventricular strain and strain rate values were compared between the study groups. Initial longitudinal and radial strain as well as strain rate values of the left ventricle were significantly lower in patients. After vitamin-D supplementation, these improved significantly in patients, whereas no significant change was observed in the control group. Our study showed that, although conventional and tissue Doppler imaging methods could not determine any effect, two-dimensional speckle-tracking echocardiography revealed the favourable effects of high-dose cholecalciferol on cardiac mechanics, implying the importance of vitamin-D supplementation in children with chronic kidney disease.

Topics: Adolescent; Adult; Calcifediol; Cardiovascular System; Case-Control Studies; Child; Child, Preschool; Cholecalciferol; Echocardiography; Female; Heart Ventricles; Humans; Male; Regression Analysis; Renal Insufficiency, Chronic; Ventricular Function, Left; Vitamin D Deficiency; Vitamins; Young Adult

Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression.. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cholecalciferol; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Renin-Angiotensin System; Vitamin D Deficiency; Vitamins

Adherence to therapy is a relevant challenge in chronic hemodialysis patients. The directly observed therapy (DOT) could be an effective method to increase adherence for specific therapies. We aimed to study the performance of DOT versus home medication. We follow the impact of providing native vitamin D directly by the nurse after a dialysis session on the 25-hydroxyvitamin [25(OH)D] concentrations.. In this observational study, we included 38 dialysis patients treated by stable dosage of cholecalciferol. DOT was implemented in December 2010. We considered the concentrations of 25-OH vitamin D three times before (T1 = June 2010, T2 = July 2010 and T3 = September 2010) and three times after the modification of prescription (T4 = February 2011, T5 = March 2011 and T6 = April 2011).. Median age was 72 [62; 79] years and 48 % were diabetics. Mean body mass index was 26 ± 5 kg/m(2) and median dialysis vintage was 20 [8; 46] months. The patients were compared to themselves. Before DOT, median concentrations of 25(OH)D were 27 (14-36), 23 (17-31), 31 (22-38) ng/mL at T1, T2 and T3, respectively. When DOT was effective, the concentrations significantly increased to 34 (28-44), 35 (29-41), 39 (32-47) ng/mL at T4, T5 and T6, respectively. Before DOT, 19 patients (50 %) reached the target of 30 ng/mL. After DOT, 29 patients (76 %) reached the target concentration of 30 ng/mL.. In hemodialysis patients, DOT is both simple and effective to increase the therapeutic impact to native vitamin D.

Topics: Aged; Biomarkers; Cholecalciferol; Dietary Supplements; Directly Observed Therapy; Female; Humans; Male; Medication Adherence; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

As cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD.. Forty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups.. Initial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment.. Our interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD.

Topics: Administration, Oral; Adolescent; Biomarkers; Calcifediol; Child; Child, Preschool; Cholecalciferol; Echocardiography; Endothelium, Vascular; Female; Humans; Male; Renal Insufficiency, Chronic; Vascular Stiffness; Vitamin D Deficiency; Vitamins; Young Adult

Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor-like receptor, and its receptor modifier, receptor activity-modifying protein 3. IMD1-53 treatment reduced vascular calcification. The expression of α-Klotho was greatly decreased in the aortas of rats with CKD but increased in the aortas of IMD1-53-treated rats with CKD. In vitro, IMD1-53 increased α-Klotho protein level in calcified vascular smooth muscle cells. α-Klotho knockdown blocked the inhibitory effect of IMD1-53 on vascular smooth muscle cell calcification and their transformation into osteoblast-like cells. The effect of IMD1-53 to upregulate α-Klotho and inhibit vascular smooth muscle cell calcification was abolished by knockdown of its receptor or its modifier protein, or treatment with the protein kinase A inhibitor H89. Thus, IMD1-53 may attenuate vascular calcification by upregulating α-Klotho via the calcitonin receptor/modifying protein complex and protein kinase A signaling.

Topics: Animals; Aorta, Thoracic; Cell Transdifferentiation; Cells, Cultured; Cholecalciferol; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Glucuronidase; Humans; Klotho Proteins; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nephrectomy; Osteoblasts; Peptide Hormones; Phenotype; Rats, Sprague-Dawley; Receptor Activity-Modifying Protein 3; Receptors, Calcitonin; Renal Insufficiency, Chronic; RNA Interference; Signal Transduction; Transfection; Up-Regulation; Vascular Calcification

In chronic kidney disease (CKD) a deficiency of 1,25-dihydroxyvitamin D is common. The aim of this review was to compare vitamin D status after oral supplementation of vitamin D3 to that of serial suberythemal irradiation in end-stage kidney disease (ESKD) patients.. Ninety-five patients, with a mean age of 62 (range=35-82) years, were treated with a mean dose of 35,000 (20,000-60,000) IU vitamin D3 per week for a period of 18 months. Fourteen patients, with a mean age of 51 (range=41-57) years, were whole-body UVB irradiated for over 6 months. From 3 hemodialysis patients skin biopsies were performed.. With oral supplementation 25(OH)D3 increased by 60%. With UV irradiation 25(OH)D3 increased by 400%. Gene expression analysis demonstrated an improvement in the vitamin D receptor (VDR) by 0.65 fold, in 1-alpha-hydroxylase (CYP27B1) by 1.0 fold, and in 25-hydroxylase (CYP2R) by 1.2 fold.. Serial suberythemal UVB irradiation of patients with CKD on dialysis is capable to improve serum 25(OH)D3 and 1,25(OH)2D3 by enhancing the skin's ability to activate vitamin D.

Topics: Adult; Aged; Aged, 80 and over; Calcifediol; Calcitriol; Cholecalciferol; Dietary Supplements; Humans; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

Vitamin D3 can be metabolized in the skin to 25(OH)D and 1,25(OH)2D because the skin expresses vitamin D-25-hydroxylase, 25(OH)D-1-alpha-hydroxylase, and the vitamin D receptor. The aim of this review was to discuss the pleiotropic effects after serial suberythemal UVB irradiation with a sun-simulating UV spectrum in end-stage kidney disease patients.. Fourteen hemodialysis patients, with a mean age of 51 (range 41-57) years, were whole-body UV irradiated over 6 months.. Patients demonstrated an increase in their hematocrit and required less erythropoietin. An increase in maximal oxygen uptake and workload capacity was associated with decreased lactic acid production. The patients demonstrated a decreased heart rate and systolic and diastolic blood pressure with an increase in the R-R-interval and the beat-to-beat-differences.. Cardiovascular disease is the most important comorbidity. Exposure to simulated sunlight that contains both UVB and UVA reduce cardiovascular risk factors and improve quality of life.

Topics: Adult; Blood Pressure; Calcifediol; Cardiovascular Diseases; Cholecalciferol; Comorbidity; Heart Rate; Humans; Kidney Failure, Chronic; Middle Aged; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Sunlight; Ultraviolet Rays; Vitamin D

Denosumab-associated hypocalcaemia (DAH) has been reported in patients with osteoporosis or metastatic bone disease and is associated with stages 4 and 5 chronic kidney disease (CKD, estimated glomerular filtration rate <30 mL/min/1.73m. Retrospective cohort study between June 2013 and June 2014 of patients administered denosumab (60/120 mg) at a tertiary hospital in Melbourne, Australia, to identify the incidence of an albumin-adjusted serum calcium concentration <2.10 mmol/L or ionized calcium <1.13 mmol/L within 6 months of treatment. Univariable and multivariable logistic regression analyses were performed to identify clinical features associated with DAH.. One hundred and fifty-five patients were administered denosumab (100 osteoporosis, 55 bone metastases). Twenty-two patients (14% [95%CI 9.1-20.7]) developed hypocalcaemia: 55% were men, and 55% had osteoporosis. Eighty-six per cent had a 25-hydroxyvitamin D concentration >50 nmol/L, and 91% were on calcium/colecalciferol supplementation. Stages 4 and 5 CKD (adjusted odd ratio [aOR] 4.71, 95%CI 1.61-13.79, p = 0.005) and male sex (aOR 4.30, 95%CI 1.69-10.96, p = 0.002) were associated with DAH. No patients were documented as having hypocalcaemic symptoms. One patient received intravenous calcium gluconate treatment.. The incidence of denosumab-associated hypocalcaemia was 14% (95%CI 9.1-20.7) within 6 months of treatment despite widespread use of appropriate calcium/colecalciferol supplementation. Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcaemia. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Aged; Aged, 80 and over; Australia; Bone Density Conservation Agents; Calcium; Cholecalciferol; Cohort Studies; Denosumab; Female; Glomerular Filtration Rate; Humans; Hypocalcemia; Incidence; Male; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Severity of Illness Index; Sex Factors; Tertiary Care Centers; Vitamin D

Vitamin D (Vit D) deficiency plays a central role in the pathogenesis of chronic kidney disease (CKD) complications, both skeletal and nonskeletal. The purpose of this study was to examine whether 25(OH)D levels and supplementation with oral cholecalciferol (Vitamin D3 (Vit D3)) are associated with morbidity and mortality among patients with significant CKD.. CKD patients attending the nephrology clinic at Shaare Zedek Medical Center between July 1, 2008 and January 31, 2012, tested at least twice for 25(OH)D levels, were enrolled. Primary endpoints included death, end-stage renal disease (ESRD) requiring start of dialysis, a rise of at least 50% in serum creatinine, or composite endpoints of the above.. A total of 516 patients were studied, of whom 178, 257, and 81 patients had baseline vitamin D levels < 5 ng/mL, 15 - 30 ng/mL, and > 30 ng/mL, respectively. We found an association between baseline 25(OH)D level below 15 ng/mL and renal outcomes (start of dialysis or a rise of at least 50% in serum creatinine) in both crude and multivariate analyses (hazard ratio (HR) 3.17, 95% CI 1.12 - 8.94). Vit D3 supplementation demonstrated beneficial effects on combined renal outcomes and death in univariate analyses (p = 0.02). Moreover, an increment of 10 ng/mL in 25(OH)D levels was associated with a 25% reduction in mortality (HR 0.755 (95% CI 0.54 - 1.00), in crude but not adjusted analyses.. Significant Vit D deficiency in CKD can serve as a biological marker indicating patients in whom adverse renal outcomes can be anticipated. Moreover, Vit D3 supplementation and rise of serum 25(OH)D levels may have beneficial influence on hard renal outcomes.
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Topics: Aged; Biomarkers; Cholecalciferol; Female; Humans; Kidney Function Tests; Male; Middle Aged; Prognosis; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Survival Rate; Vitamin D; Vitamin D Deficiency; Vitamins

Mini review summarizes the results of our studies focused on elucidation of the pathophysiological mechanisms of altered calcium homeostasis in nonexcitable cells from patients with early stages of chronic kidney disease (CKD), as well as on determining the effect of vitamin D3 supplementation on these mechanisms. The basic mechanisms of calcium entry to and removal of the cell are already changed in early stages of CKD. These disturbances cause an increased the concentration of cytosolic free calcium ([Ca2+]i), which may change a number of cellular processes, and the expression of various signaling molecules. Vitamin D3 supplementation is a standard procedure of vitamin D insufficiency/ deficiency correction in these patients. The pleiotropic effects of vitamin D may be involved in the modulation of cellular calcium homeostasis. Vitamin D3 supplementation resulted in a reduction in [Ca2+]i by affecting of specific transport systems of calcium cations entry to and removal of the cell. The normalization [Ca2+]i can have a beneficial effect on intracellular signalling, and thus positively influence the functioning of cells, tissues or organs.Key words: cellular calcium homeostasis - chronic kidney disease - intracellular calcium - vitamin D.

Topics: Calcium; Cholecalciferol; Homeostasis; Humans; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins

Intracellular calcium concentration in peripheral blood mononuclear cells (PBMCs) of patients with chronic kidney disease (CKD) is significantly increased, and the regulatory mechanisms maintaining cellular calcium homeostasis are impaired. The purpose of this study was to examine the effect of vitamin D3 on predominant regulatory mechanisms of cell calcium homeostasis. The study involved 16 CKD stages 2-3 patients with vitamin D deficiency treated with cholecalciferol 7000-14000 IU/week for 6 months. The regulatory mechanisms of calcium signaling were studied in PBMCs and red blood cells. After vitamin D3 supplementation, serum concentration of 25(OH)D3 increased (P < 0.001) and [Ca(2+)]i decreased (P < 0.001). The differences in [Ca(2+)]i were inversely related to differences in 25(OH)D3 concentration (P < 0.01). Vitamin D3 supplementation decreased the calcium entry through calcium release activated calcium (CRAC) channels and purinergic P2X7 channels. The function of P2X7 receptors was changed in comparison with their baseline status, and the expression of these receptors was reduced. There was no effect of vitamin D3 on P2X7 pores and activity of plasma membrane Ca(2+)-ATPases. Vitamin D3 supplementation had a beneficial effect on [Ca(2+)]i decreasing calcium entry via CRAC and P2X7 channels and reducing P2X7 receptors expression.

Topics: Adult; Aged; Aged, 80 and over; Calcium; Calcium Signaling; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Female; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Receptors, Purinergic P2X7; Renal Insufficiency, Chronic; Vitamin D Deficiency

Topics: Aged, 80 and over; Bone Density Conservation Agents; Calcitriol; Calcium Carbonate; Cholecalciferol; Denosumab; Female; Fractures, Bone; Humans; Hypercalcemia; Hypocalcemia; Medication Errors; Renal Insufficiency, Chronic; Tetany

Vitamin D deficiency is highly prevalent in dialysis patients. Whether substitution of native vitamin D in these patients is beneficial is a matter of ongoing discussion, as is the optimal dosing schedule. The purpose of this study was to investigate the efficacy and safety of a body-weight adapted oral dosing regimen of cholecalciferol in dialysis patients.. In a prospective single-center study 56 prevalent dialysis patients with a baseline 25OHD3 level <20 ng/mL received 100 IU of cholecalciferol per kg body weight once weekly orally for 26 weeks. 25OHD3 was measured at baseline and at study end, iPTH every three months, serum calcium and phosphorous monthly. Concurrent medication including phosphate binders, calcitriol and cinacalcet and dialysate calcium concentration remained unchanged throughout the study.. Baseline 25OHD3 was 9.9 ± 4.1 ng/mL and increased to 26.1 ± 8.8 ng/mL (P = 0.01). Fourteen patients (27 %) achieved a level > 30 ng/mL and all others above 20 ng/mL. Cinacalcet therapy was positively associated with the increase in 25OHD3 (P = 0.024). The plasma iPTH level significantly decreased from median 362 pg/mL to 297 pg/mL (P = 0.01). This decline was more pronounced in patients with higher baseline iPTH levels (P < 0.01) and differed significantly dependent on concurrent calcitriol therapy. A significant iPTH decrease was observed in patients receiving calcitriol (P = 0.031). Serum calcium and phosphorous did not change significantly throughout the study period. Cholecalciferol substitution was well tolerated without adverse effects.. The dosing regimen of oral cholecalciferol supplementation with 100 IU per kg body weight per week for 26 weeks in dialysis patients with vitamin D deficiency causes a significant increase in 25OHD3 close to the supposed target level of 30 ng/mL and a significant reduction in iPTH, without affecting serum calcium or phosphorous levels.

Topics: Administration, Oral; Aged; Aged, 80 and over; Body Weight; Calcifediol; Calcimimetic Agents; Calcitriol; Calcium; Cholecalciferol; Cinacalcet; Drug Dosage Calculations; Drug Substitution; Female; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins

We aimed to evaluate the vitamin D status, the effect of cholecalciferol supplementation, and the factors associated with vitamin D restoration in nondialytic patients with chronic kidney disease (CKD).. The present study was a prospective open-label trial.. This study took place at the Seoul National University Boramae Medical Center.. Patients with nondialytic CKD (estimated glomerular filtration rate [eGFR] 10-59 mL/min per 1.73 m(2)) participated in this study.. Vitamin D status in 210 CKD patients was assessed and the patients with vitamin D deficiency (<30 ng/mL) were administered cholecalciferol (1,000 IU/day) for 6 months.. The restoration rate of vitamin D deficiency at 3 and 6 months and the response-related factors were analyzed.. The prevalence of vitamin D deficiency was 40.7% in CKD Stage 3, 61.5% in Stage 4, and 85.7% in Stage 5. The subgroup with vitamin D deficiency had a greater proportion of patients with diabetes, lower eGFR, and higher proteinuria. With the supplementation, 52 patients (76.5%) reached levels of 25-hydroxy vitamin D (25(OH)D) of 30 ng/mL or greater at 3 months, and the restoration of vitamin D was observed in 61 patients (89.7%) at 6 months. Lower levels of 25(OH)D and a higher amount of proteinuria at baseline were the factors associated with lower response to vitamin D supplementation.. Vitamin D deficiency rate was high in nondialytic CKD patients, and the proportion increased as renal function decreased. A higher amount of proteinuria was the independent risk factor of nonresponse with supplementation. Vitamin D was replenished in most patients with cholecalciferol supplementation without any significant adverse effects.

Topics: Aged; Cholecalciferol; Dietary Supplements; Female; Glomerular Filtration Rate; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

This study examined rates and determinants of vitamin D supplementation among Chronic Renal Insufficiency Cohort (CRIC) participants and determined the association between dose and 25-hydroxyvitamin D (25(OH)D) level. The 2010 Institute of Medicine Report noted a significant increase in vitamin D supplementation in the general population, but use in chronic kidney disease (CKD) is unknown.. CRIC is a multicenter prospective observational cohort study of 3,939 participants with a median baseline age of 60 and an estimated glomerular filtration rate (eGFR) of 42.1 mL/minute per 1.73 m2. Of the cohort, 54.9% was male, 42.1% were Black, and 48.4% were diabetic. Multivariable logistic generalized estimating equations were used to examine determinants of supplementation use assessed annually between 2003 and 2011. Cross-sectional linear regression models, based on a subset of 1,155 participants, assessed associations between supplement dose and 25(OH)D level, measured by high-performance liquid chromatography coupled with tandem mass spectrometry.. The proportion of participants reporting supplement use increased (P < .0001), from 10% at baseline to 44% at 7-year follow-up visits. This was largely due to initiation of products containing only ergocalciferol or cholecalciferol. The odds of supplementation were greater in older, female, non-Black, married participants with greater education and lower body mass index. Among participants taking supplementation, dose was positively associated with 25(OH)D level, adjusted for race, season, diabetes, dietary intake, eGFR, and proteinuria. Only 3.8% of non-Black and 16.5% of Black participants taking a supplement were deficient (<20 ng/mL), whereas 22.7% of non-Black and 62.4% of black participants not reporting supplement use were deficient.. Vitamin D supplementation rates rose significantly among CRIC participants over 7 years of follow-up and were associated with greater serum 25(OH)D levels. Studies of vitamin D levels on clinical outcomes in CKD and future vitamin D interventional studies should consider these changes in supplementation practices.

Topics: Age Factors; Aged; Cholecalciferol; Cohort Studies; Cross-Sectional Studies; Dietary Supplements; Ergocalciferols; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Sex Factors; Vitamin D

Topics: Aged, 80 and over; Calcium; Cholecalciferol; Diagnosis, Differential; Diphosphonates; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Osteoporosis; Renal Insufficiency, Chronic

This study investigated the effects of hypertension on regional aortic biomechanical and structural properties in three rat models of vascular calcification: the hypertensive Lewis polycystic kidney (LPK; n = 13) model of chronic kidney disease, spontaneously hypertensive rats (SHRs; n = 12), and calcification in normotensive Lewis rats induced by vitamin D3 and nicotine (VDN; n = 8). Lewis and Wistar-Kyoto rats were controls. Thoracic and abdominal aortic stiffness parameters were assessed by tensile testing. In models where aortic stiffness differences compared with controls existed in both thoracic and abdominal segments, an additional cohort was quantified by histology for thoracic and abdominal aortic elastin, collagen, and calcification. LPK and VDN animals had higher thoracic breaking strain than control animals (P < 0.01 and P < 0.05, respectively) and lower energy absorption within the tensile curve of the abdominal aorta (P < 0.05). SHRs had a lower abdominal breaking stress than Wistar-Kyoto rats. LPK and VDN rats had more elastic lamellae fractures than control rats (P < 0.001), which were associated with calcium deposition (thoracic R = 0.37, P = 0.048; abdominal: R = 0.40, P = 0.046). LPK rats had higher nuclear density than control rats (P < 0.01), which was also evident in the thoracic but not abdominal aorta of VDN rats (P < 0.01). In LPK and VDN rats, but not in control rats, media thickness and cross-sectional area were at least 1.5-fold greater in thoracic than abdominal regions. The calcification models chronic kidney disease and induced calcification in normotension caused differences in regional aortic stiffness not seen in a genetic form of hypertension. Detrimental abdominal aortic remodeling but lower stiffness in the thoracic aorta with disease indicates possible compensatory mechanisms in the proximal aorta.

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; Biomechanical Phenomena; Cholecalciferol; Collagen; Disease Models, Animal; Elastin; Female; Hemodynamics; Hypertension; Male; Oxazines; Rats; Rats, Inbred Lew; Rats, Inbred SHR; Rats, Inbred WKY; Renal Insufficiency, Chronic; Tensile Strength; Vascular Calcification; Vascular Stiffness

The optimal circulating concentration of 25(OH) vitamin D is controversial.. The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement.. Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m(2) (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14).. The study was conducted at the Veterans Affairs clinics.. Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment.. Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P = .001; 12.2 ± 9 ηg/mL, P = .0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P = .0024; 1.0 ± 0.72 ηg/mL P = .0002), and reduced serum PTH (-11 ± 21 pg/mL, P = .0292; -42 ± 68 pg/mL, P = .0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P = .01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mL P ≤ .05) without changing 24,25(OH)2D, FGF-23 or PTH levels.. Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL. In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.

Topics: 24,25-Dihydroxyvitamin D 3; Aged; Cholecalciferol; Drug Monitoring; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Kidney; Male; Middle Aged; Multivariate Analysis; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

The benefits of and thresholds for 25-hydroxyvitamin D administration in individuals with chronic kidney disease (CKD) remain uncertain. In this report, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) endeavors to provide health care providers with the latest information on a controversial area in the management of CKD, the role for nutritional vitamin D. Although knowledge of the biological mechanisms of vitamin D for bone maintenance in individuals with all stages of CKD has expanded, no consensus currently exists within the medical community regarding methods for 25-hydroxyvitamin D supplementation or optimal 25-hydroxyvitamin D levels in individuals with CKD. Within this report, existing CKD guidelines are summarized and scrutinized and ongoing clinical trials are cited as sources for future guidance on the optimal management of vitamin D in CKD.

Topics: Bone Density Conservation Agents; Cholecalciferol; Dietary Supplements; Disease Management; Disease Progression; Ergocalciferols; Glomerular Filtration Rate; Humans; Outcome Assessment, Health Care; Patient Acuity; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Risk Assessment; Vitamin D

Topics: Cholecalciferol; Female; Humans; Male; Renal Dialysis; Renal Insufficiency, Chronic

Vitamin D deficiency is common in the general population and even more prevalent in patients with chronic kidney disease (CKD). Low 25-hydroxyvitamin D [25(OH)D] levels have been associated with cardiovascular disease, though a definitive mechanistic link has not been established. Further, it is unclear if repleting vitamin D mitigates the excess risk observed in epidemiologic studies. Because vitamin D may regulate innate immunity and gut epithelial differentiation, we hypothesized that oral cholecalciferol (D3) would result in decreased blood endotoxin activity, a potential risk factor for cardiovascular disease. STUDY DESIGN, SETTING & PARTICIPANTS, INTERVENTION: We studied 12 stable outpatients with CKD stage 3 and 25(OH)D deficiency, who received D3 30,000 units weekly for 8 weeks. The primary endpoint was the change in blood endotoxin activity.. Baseline endotoxin activity correlated with 25(OH)D levels (r = -0.60, p = 0.04). Endotoxin activity decreased by 25% from baseline (p = 0.03). Despite the decrease in endotoxin activity, there was no change in intestinal permeability.. The results of this study suggest that vitamin D repletion therapy may have an effect on endotoxin activity in early CKD. Further intervention studies using vitamin D in the CKD population are required.

Topics: Aged; Biomarkers; Cholecalciferol; Cytokines; Endotoxins; Female; Humans; Inflammation; Intestinal Mucosa; Intestines; Male; Middle Aged; Permeability; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification.

Topics: Acetylcholine; Animals; Calcinosis; Cardiovascular Diseases; Cell Line; Cell Proliferation; Cell Survival; Cholecalciferol; Ergocalciferols; Myocytes, Cardiac; Rats; Renal Insufficiency, Chronic

Human marrow stromal cells (hMSCs) are targets of 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] action to promote their differentiation to osteoblasts, but they also participate in vitamin D metabolism by converting 25-dihydroxyvitamin D3 [25(OH)D3] to 1α,25(OH)2D3 by 1α-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is associated with impaired renal biosynthesis of 1α,25(OH)2D, low bone mass, and increased fracture risk. We tested whether CKD influences hMSCs' responses to vitamin D3 metabolites. The hMSCs were obtained from tissues discarded during arthroplasty for hip osteoarthrosis, including a subject who had been undergoing hemodialysis for 2+ years. There was a significant positive correlation between in vitro stimulation of osteoblastogenesis (alkaline phosphatase activity) by 1α,25(OH)2D3 and subjects' estimated glomerular filtration rate (eGFR, r=0.47, p=0.015, n=26, 56-83 years of age). Osteoblastogenesis was stimulated in hMSCs from both the hemodialysis and control subjects by 1α,25(OH)2D3 (10μM), 25(OH)D3 (100μM), or D3 (1000μM). Thus, vitamin D metabolism may play an autocrine/paracrine role in osteoblast differentiation of hMSCs. These findings suggest that in CKD patients 25(OH)D-sufficiency may play an important role in skeletal health; osteoblastic bone formation in CKD patients may not be optimal unless there is sufficient serum 25(OH)D substrate for the MSCs to synthesize and respond to local 1α,25(OH)2D. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Topics: Aged; Calcifediol; Calcitriol; Cell Differentiation; Cholecalciferol; Female; Humans; Male; Mesenchymal Stem Cells; Middle Aged; Renal Insufficiency, Chronic; Vitamin D

Hypovitaminosis D and chronic kidney disease (CKD) are highly prevalent in older adults. The factors correlating with 25-OH-vitamin D and PTH levels were analyzed in older adults with and without CKD.. We performed a cross-sectional analysis embedded within the BELFRAIL study.. A population-based prospective cohort study of the very elderly in Belgium.. 325 participants, all aged 80 or older.. Time of year and LAPAQ score were used as proxies for sunshine exposure. Vitamin D3 supplementation, gender, institutionalisation, age, level of education, and serum calcium and phosphorus level were examined as possible confounders in the analyses.. There was no correlation between the presence of CKD and low 25-OH-vitamin D levels, but there was a significant (p<0.01) correlation between CKD and high PTH levels. Among the participants with a normal eGFR, the LAPACQ score, vitamin D supplementation, season, log PTH value and eGFR were correlated with log 25-OH-vitamin D levels. Among the participants with CKD, only vitamin D supplementation, log PTH levels and serum calcium levels were correlated with log 25-OH-vitamin D levels. Gender, log 25-OH-vitamin D values, serum calcium and phosphorus levels and eGFR were correlated with log PTH values in the patients with normal eGFR. Log 25-OH-vitamin D values, serum phosphorus levels, vitamin D supplementation (p=0.07), season (p=0.10) and eGFR were correlated with log PTH values in the patients with CKD.. Exposure to sunshine and an active lifestyle were correlated with higher 25-OH-vitamin D levels in older adults without CKD. The PTH level in patients with CKD may be influenced by the season.

Topics: Aged, 80 and over; Belgium; Calcium; Cholecalciferol; Dietary Supplements; Exercise; Female; Glomerular Filtration Rate; Humans; Kidney; Life Style; Male; Parathyroid Hormone; Phosphorus; Prospective Studies; Reference Values; Renal Insufficiency, Chronic; Seasons; Sex Factors; Sunlight; Vitamin D; Vitamin D Deficiency

To investigate the effects of oral cholecalciferol on the levels of vitamin D3 and intact parathyroid hormone (iPTH) in children with chronic kidney disease (CKD).. We conducted a prospective uncontrolled observational study at the Pediatric Nephrology Clinic of King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between January and October 2011 to assess serum 25-hydroxyvitamin D3 (25[OH]D) and iPTH in children with CKD stages 2-5. Children with low vitamin D3 levels were commenced on cholecalciferol, 2000 IU/day. Their 25(OH)D3 and iPTH levels were reassessed, first after 3 months, and then after 6 months. Data analysis was performed using the Statistical Package for Social Sciences. Paired t-test was used to compare results before and after treatment.. Forty-five children (31 boys and 14 girls) were included in the study. Their mean+/-SD age was 9.6 +/- 4.6 years. There was significant improvement in 25(OH)D3 after 3 months (14.2 +/- 8.2 - 20 +/- 11.1 ng/mL) (p<0.001). However, only 5 children reached levels >/=30 ng/mL. There was no further improvement after 6 months of treatment (20.17 +/- 13.4 ng/mL) (p=0.65). There was no improvement in iPTH levels after 3 and 6 months. No changes were also observed in the levels of calcium, phosphate, alkaline phosphatase, or creatinine.. The administration of oral vitamin D3 at 2000 IU/day resulted in significant improvement of vitamin D levels in children with CKD, but normalized only in 11% of the patients. The treatment had no effect on iPTH levels.

Topics: Adolescent; Child; Child, Preschool; Cholecalciferol; Female; Humans; Male; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins