scholarly journals A novel assay to measure calcification propensity: from laboratory to humans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
M. Mar Perez ◽  
Miguel D. Ferrer ◽  
Marta Lazo-Rodriguez ◽  
Ana Zeralda Canals ◽  
Elisenda Banon-Maneus ◽  
...  
Keyword(s):  
Vitamin D ◽  
Clinical Trials ◽  
Calcium Phosphate ◽  
Rat Model ◽  
Plasma Calcium ◽  
Morbidity And Mortality ◽  
Predictive Tool ◽  
Pharmacodynamic Effects ◽  
Calcification Inhibitors ◽  
Spectrometric Measurements

Abstract Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N = 38) injected with vitamin D (days 1–3) to induce CVC were infused with saline or SNF472 (days 1–12). Inhibition of CVC was 50–65% with SNF472 3 mg/kg and ~ 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r = 0.628, P = 0.005). In patients with calciphylaxis (N = 14), infusion of SNF472 (~ 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N = 274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r = 0.401, P = 0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors.

Normal plasma calcium, phosphate, and parathyroid hormone levels during 1,25(OH)2D3 infusions in rats

1992 ◽  
Vol 262 (1) ◽  
pp. E126-E129 ◽  
Author(s):  
J. Fox ◽  
U. Kollenkirchen
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Calcium Phosphate ◽  
Cell Function ◽  
Plasma Calcium ◽  
Dihydroxyvitamin D3 ◽  
Subcutaneous Infusion ◽  
Cellular Effects ◽  
Precise Role

The changes in plasma calcium, phosphate, and parathyroid hormone (PTH) levels that accompany 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] administration to experimental animals represent major obstacles to determining the precise role that 1,25(OH)2D3 plays in cell function in vivo. These difficulties arise because calcium, phosphate, and PTH have major cellular effects independent of 1,25(OH)2D3. To circumvent this obstacle, we have developed an animal model in which plasma 1,25(OH)2D3 levels were raised from 20 +/- 3 to 96 +/- 19, 240 +/- 49, and 459 +/- 66 pg/ml in vitamin D-deficient rats without influencing plasma ionized calcium, total calcium, phosphate, or NH2-terminal immunoreactive PTH (irPTH) levels. The elevated 1,25(OH)2D3 levels were achieved by constant subcutaneous infusion of 1,25(OH)2D3 using osmotic minipumps. Progressive reduction in the calcium and phosphorus content of the diet as the 1,25(OH)2D3 infusion rate was increased prevented concomitant changes in plasma calcium, phosphate, and irPTH levels. This experimental model, in conjunction with our previously developed normocalcemic rat model of vitamin D deficiency, provides a powerful experimental tool for the investigation of 1,25(OH)2D3 effects in vivo in the absence of concomitant changes in other parameters of calcium homeostasis.

Use of pre-operative calcium and vitamin D supplementation to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy: a systematic review

2021 ◽  
pp. 1-6
Author(s):  
A S Khatiwada ◽  
A S Harris
Keyword(s):  
Systematic Review ◽  
Vitamin D ◽  
Clinical Trials ◽  
Total Thyroidectomy ◽  
Risk Reduction ◽  
Operative Treatment ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Vitamin D Supplementation ◽  
Absolute Reduction

Abstract Objective This systematic review aimed to establish the evidence behind the use of pre-operative calcium, vitamin D or both calcium and vitamin D to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy. Method This review included prospective clinical trials on adult human patients that were published in English and which studied the effects of pre-operative supplementation with calcium, vitamin D or both calcium and vitamin D on the rate of post-operative hypocalcaemia following total thyroidectomy. Results Seven out of the nine trials included reported statistically significantly reduced rates of post-operative laboratory hypocalcaemia (absolute risk reduction, 13–59 per cent) and symptomatic hypocalcaemia (absolute reduction, 11–40 per cent) following pre-operative supplementation. Conclusion Pre-operative treatment with calcium, vitamin D or both calcium and vitamin D reduces the risk of post-operative hypocalcaemia and should be considered in patients undergoing total thyroidectomy.

scholarly journals Efficacy of weekly administration of cholecalciferol on parathyroid hormone in stable kidney-transplanted patients with CKD stage 1–3

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Stefania Sella ◽  
Luciana Bonfante ◽  
Maria Fusaro ◽  
Flavia Neri ◽  
Mario Plebani ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Calcium Phosphate ◽  
Serum Calcium ◽  
Chronic Kidney Disease Stage ◽  
Serum Vitamin ◽  
Disease Stage ◽  
Weekly Administration ◽  
Ckd Stage ◽  
Stage 1

AbstractObjectivesKidney 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.MethodsIn 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.ResultsAt 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).ConclusionsWeekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.

scholarly journals Effects of the Use of Non-Calcium Phosphate Binders in the Control and Outcome of Vascular Calcifications: A Review of Clinical Trials on CKD Patients

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Piergiorgio Bolasco
Keyword(s):  
Calcium Phosphate ◽  
Mortality Rates ◽  
Morbidity And Mortality ◽  
Phosphate Binders ◽  
Vascular Calcifications ◽  
Mineral Bone Disorder ◽  
Bone Disorder ◽  
Advanced Stages ◽  
The Impact ◽  
Specific Contribution

Vascular calcifications produce a high impact on morbidity and mortality rates in patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD). Effects are manifested from the more advanced stages of CKD (stages 3-4), particularly in patients undergoing dialysis (CKD5D). In recent years, a large number of therapeutic options have been successfully used in the treatment of secondary hyperparathyroidism (SHPT), despite eliciting less marked effects on nonbone calcifications associated with CKD-MBD. In addition to the use of Vitamin D and analogues, more recently treatment with calcimimetic drugs has also been undertaken. The present paper aims to analyze comparative and efficacy studies undertaken to assess particularly the impact on morbidity and mortality rates of non-calcium phosphate binders. Moreover, the mechanism of action underlying the depositing of calcium and phosphate along blood vessel walls, irrespective of the specific contribution provided in reducing the typical phosphate levels observed in CKD largely at more advanced stages of the disease, will be investigated. The aim of this paper therefore is to evaluate which phosphate binders are characterised by the above action and the mechanisms through which these are manifested.

scholarly journals Assessment of Biochemical and Densitometric Markers of Calcium-Phosphate Metabolism in the Groups of Patients with Multiple Sclerosis Selected due to the Serum Level of Vitamin D3

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Natalia Niedziela ◽  
Krystyna Pierzchała ◽  
Jolanta Zalejska-Fiolka ◽  
Jacek T. Niedziela ◽  
Ewa Romuk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Calcium Phosphate ◽  
Serum Level ◽  
Clinical Stage ◽  
Phosphate Metabolism ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Calcium Phosphate Metabolism

Background. In addition to the widely known effect of vitamin D3 (vitD3) on the skeleton, its role in the regulation of the immune response was also confirmed. Aim. The assessment of biochemical and densitometric markers of calcium-phosphate metabolism in the groups of patients with relapsing-remitting multiple sclerosis (RRMS) selected due to the serum level of vitamin D3. Methods. The concentrations of biochemical markers and indices of lumbar spine bone densitometry (DXA) were determined in 82 patients divided into vitamin D3 deficiency (VitDd), insufficiency (VitDi), and normal vitamin D3 level (VitDn) subgroups. Results. The highest level of the parathyroid hormone (PTH) and the highest prevalence of hypophosphatemia and osteopenia were demonstrated in VitDd group compared to VitDi and VitDn. However, in VitDd, VitDi, and VitDn subgroups no significant differences were observed in the levels of alkaline phosphatase (ALP) and ionized calcium (Ca2+) and in DXA indices. A negative correlation was observed between the level of vitamin D3 and the Expanded Disability Status Scale (EDSS) in the whole MS group. The subgroups were significantly different with respect to the EDSS scores and the frequency of complaints related to walking according to the EQ-5D. Conclusions. It is necessary to assess calcium-phosphate metabolism and supplementation of vitamin D3 in RRMS patients. The higher the clinical stage of the disease assessed with the EDSS, the lower the level of vitamin D3 in blood serum. Subjectively reported complaints related to difficulties with walking were reflected in the EDSS in VitDd patients.

scholarly journals The role of vitamin D in metabolic disturbances in polycystic ovary syndrome: a systematic review

2013 ◽  
Vol 169 (6) ◽  
pp. 853-865 ◽  
Author(s):  
Y H M Krul-Poel ◽  
C Snackey ◽  
Y Louwers ◽  
P Lips ◽  
C B Lambalk ◽  
...  
Keyword(s):  
Systematic Review ◽  
Vitamin D ◽  
Clinical Trials ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Vitamin D Status ◽  
Regression Analyses ◽  
Metabolic Disturbances ◽  
Ovary Syndrome ◽  
Weighted Means

ContextMetabolic disturbances, in particular, insulin resistance (IR) and dyslipidemia, are common in women suffering from polycystic ovary syndrome (PCOS). Evidence is accumulating that vitamin D status may contribute to the development of metabolic disturbances in PCOS.ObjectiveThe aim of this study was to carry out a systematic review addressing the association between vitamin D status, vitamin D receptor polymorphisms, and/or polymorphisms related to vitamin D metabolism and metabolic disturbances in women with PCOS.Design and methodsA systematic search of electronic databases was carried out up to January 2013 for observational studies and clinical trials in women suffering from PCOS with outcome measures that were related to vitamin D status. We conducted univariate and multivariate regression analyses of the weighted means to gain insights into the association between vitamin D, BMI, and IR based on existing literature.ResultsWe found 29 eligible trials with inconsistency in their results. One well-designed randomized controlled trial has been carried out until now. Univariate regression analyses of the weighted means revealed vitamin D to be a significant and independent predictor of IR in both PCOS and control women. The significance disappeared after adjustment for BMI in PCOS women.ConclusionsCurrent evidence suggests an inverse association between vitamin D status and metabolic disturbances in PCOS. Owing to the heterogeneity of the studies, it is hard to draw a definite conclusion. The causal relationship between vitamin D status and metabolic disturbances in PCOS remains to be determined in well-designed placebo-controlled randomized clinical trials.

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