scholarly journals The Emerging Role of Nutritional Vitamin D in Secondary Hyperparathyroidism in CKD

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1890 ◽  
Author(s):  
Chien-Lin Lu ◽  
Dong-Feng Yeih ◽  
Yi-Chou Hou ◽  
Guey-Mei Jow ◽  
Zong-Yu Li ◽  
...  
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Fibroblast Growth Factor 23 ◽  
Vitamin D Binding Protein ◽  
Hydroxylase Activity ◽  
Fgf 23 ◽  
Oxyphil Cell ◽  
Pth Level ◽  
Nutritional Vitamin

In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D) synthesis; thereby increasing parathyroid hormone (PTH) production. FGF-23 acts on the parathyroid gland (PTG) to increase 1α-hydroxylase activity and results in increase intra-gland 1,25D production that attenuates PTH secretion efficiently if sufficient 25D are available. Interesting, calcimimetics can further increase PTG 1α-hydroxylase activity that emphasizes the demand for nutritional vitamin D (NVD) under high PTH status. In addition, the changes in hydroxylase enzyme activity highlight the greater parathyroid 25-hydroxyvitmain D (25D) requirement in secondary hyperparathyroidism (SHPT); the higher proportion of oxyphil cells as hyperplastic parathyroid progression; lower cytosolic vitamin D binding protein (DBP) content in the oxyphil cell; and calcitriol promote vitamin D degradation are all possible reasons supports nutritional vitamin D (NVD; e.g., Cholecalciferol) supplement is crucial in SHPT. Clinically, NVD can effectively restore serum 25D concentration and prevent the further increase in PTH level. Therefore, NVD might have the benefit of alleviating the development of SHPT in early CKD and further lowering PTH in moderate to severe SHPT in dialysis patients.

scholarly journals Inhibition of Fibroblast Growth Factor-23 (FGF-23) As a Novel Strategy to Target Bone and Hematopoietic Stem Cell Niche Defects in Beta-Thalassemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Annamaria Aprile ◽  
Laura Raggi ◽  
Mariangela Storto ◽  
Isabella Villa ◽  
Sarah Marktel ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Beta Thalassemia ◽  
Causative Role ◽  
Ineffective Erythropoiesis ◽  
Hematopoietic Stem ◽  
Bm Niche ◽  
Fgf 23

In the last decade many studies unraveled the bone marrow (BM) niche regulation and crosstalk with hematopoietic stem cells (HSC) in steady state conditions and malignancies, but HSC-niche interactions are still underexplored in hematological inherited disorders. We have recently provided the first demonstration of impaired HSC function caused by an altered BM niche in a non-malignant disease, beta-thalassemia (BT) (Aprile et al., Blood 2020). BT is a congenital hemoglobin disorder resulting in severe anemia, ineffective erythropoiesis and multi-organ secondary complications, such as bone defects. It is one of the most globally widespread monogenic diseases, which can be cured by transplantation of HSC from compatible healthy donors or autologous HSC from patients upon gene therapy. Cases of graft failure have been reported, but causes have not been deeply investigated and might include an impaired HSC function and a defective supporting activity of the BM niche, worsened by age and disease progression. We showed that the prolonged residence of HSC into an altered BM stromal niche in BT Hbbth3/+ (th3) mice negatively affects stem cell number, quiescence and self-renewal. Moreover, we demonstrated that correction of HSC-stromal niche crosstalk rescues BT HSC function by in vivo reactivation of parathyroid hormone (PTH) signaling. Consistently with the common finding of osteoporosis in BT patients, we found reduced bone deposition and low levels of PTH also in the murine model. We investigated the potential mechanisms underlying the decreased PTH and bone defect and we focused on the role of fibroblast growth factor-23 (FGF-23). FGF-23 is a systemic hormone mainly secreted by osteocytes, which acts as negative regulator of bone metabolism by inhibiting bone mineralization and PTH production by parathyroid glands. Since FGF-23 is positively modulated by the anemia-related factor erythropoietin (EPO), we hypothesized that the high EPO levels in BT, subsequent to ineffective erythropoiesis, might contribute to increase FGF-23. We measured high levels of circulating FGF-23 in th3 mice (wt vs. th3: 399.7±69.77 vs. 1975±209.3 pg/ml, p<0.01) and also in BT patients (HD vs. THAL: 94.2±3.8 vs. 125.8±9.2 RU/ml, p<0.05). To provide proof of concept data of the causative role of FGF-23 on BT bone and stromal niche defects, we inhibited FGF-23 signaling. FGF-23 inhibition by in vivo administration of FGF-23 blocking peptide rescued the bone defect in th3 mice, by increasing trabecular bone mineral density (th3 vs. th3+FGF23inh: 117.7±3.3 vs. 181.1±6.9 mg/cm3, p<0.0001). Importantly, the treatment restored the frequency of HSC to levels comparable to wild-type controls by expanding the pool of quiescent cells (th3 vs. th3+FGF23inh: 0.03±0.002 vs. 0.07±0.0% on Linneg BM cells, p<0.0001). Consistently, we found increased the expression of key molecules by bone cells, such as Jagged-1 and osteopontin, involved in the functional crosstalk between HSC and the stromal niche. Interestingly, FGF-23 inhibition had also a positive anti-apoptotic effect on the expanded BM erythroid compartment, promoting the maturation of erythroid precursors, as already shown in models of secondary anemias. Preliminary evidence in BT patients showed negative correlations between FGF-23 levels and markers of bone homeostasis (e.g. osteocalcin and vitamin D) and positive correlations with makers of ineffective erythropoiesis (e.g. reticulocytes), thus proposing FGF-23 as the molecule at the crossroads of erythropoiesis and bone metabolism in BT. In vivo studies and molecular analysis in th3 mice and patients' samples will better unravel the causative role of EPO on FGF-23 levels in BT and the negative impact of high FGF-23 on bone mineralization and BM stromal niche-HSC interactions. Our findings uncover an underexplored role of FGF-23 in bone and BM niche defects in BT, as a condition of severe anemia and chronic EPO stimulation. The inhibition of FGF-23 signaling might provide a novel strategy to ameliorate bone compartment and restore HSC-BM niche interactions in BT, with a potential translational relevance in improving HSC transplantation approaches. Disclosures Motta: Sanofi Genzyme: Honoraria. Cappellini:BMS: Honoraria; CRISPR Therapeutics, Novartis, Vifor Pharma: Membership on an entity's Board of Directors or advisory committees; Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Role of nutritional vitamin D in osteoporosis treatment

2018 ◽  
Vol 484 ◽  
pp. 179-191 ◽  
Author(s):  
Yi-Chou Hou ◽  
Chia-Chao Wu ◽  
Min-Tser Liao ◽  
Jia-Fwu Shyu ◽  
Chi-Feng Hung ◽  
...  
Keyword(s):  
Vitamin D ◽  
Osteoporosis Treatment ◽  
Nutritional Vitamin

scholarly journals Severity of Vitamin D Deficiency Predicts Mortality in Ischemic Stroke Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jarosław Wajda ◽  
Maciej Świat ◽  
Aleksander J. Owczarek ◽  
Aniceta Brzozowska ◽  
Magdalena Olszanecka-Glinianowicz ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ischemic Stroke ◽  
Secondary Hyperparathyroidism ◽  
Functional Status ◽  
Fibroblast Growth Factor 23 ◽  
Mortality Rates ◽  
Mortality Data ◽  
Risk Of Death ◽  
Increased Risk ◽  
Cox Proportional Hazard Regression

Background. Vitamin D (VD) deficiency is considered an independent risk factor for death due to cardiovascular events including ischemic stroke (IS). We assessed the hypothesis that decreased levels of 25-hydroxyvitamin D (25-OH-D) are associated with increased risk of mortality in patients with IS. Methods. Serum 25-OH-D, intact parathyroid hormone (iPTH), and intact fibroblast growth factor 23 (iFGF23) levels were assessed in serum of 240 consecutive patients admitted within the 24 hours after the onset of IS. Mortality data was obtained from the local registry office. Results. Only three subjects (1.3%) had an optimal 25-OH-D level (30-80 ng/mL), 25 (10.4%) had a mildly reduced (insufficient) level, 61 (25.4%) had moderate deficiency, and 151 (62.9%) had a severe VD deficiency. 20% subjects had secondary hyperparathyroidism. The serum 25-OH-D level was significantly lower than that in 480 matched subjects (9.9±7.1 vs. 21.0±8.7 ng/mL). Of all the patients, 79 (32.9%) died during follow-up observation (44.9 months). The mortality rates (per year) were 4.81 and 1.89 in a group with and without severe VD deficiency, respectively (incidence rate ratio: 2.52; 95% CI: 1.44–4.68). There was no effect of secondary hyperparathyroidism and iFGF23 levels on mortality rates. Age, 25−OH−D<10 ng/mL, and functional status (modified Rankin scale) were significant factors increasing the risk of death in multivariable Cox proportional hazard regression test. Conclusions. Severe VD deficiency is an emerging, strong negative predictor for survival after IS, independent of age and functional status. VD supplementation in IS survivals may be considered due to high prevalence of its deficiency. However, it is uncertain whether it will improve their survival.

P1823THE ROLE OF FGF-23 IN CKD PROGRESSION IN CHILDREN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Assiya Kanatbayeva ◽  
Harika Alpay ◽  
Aigul Balmukhanova ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Fibroblast Growth Factor 23 ◽  
Public Health Issue ◽  
Control Group ◽  
Healthy Individuals ◽  
Ckd Progression ◽  
Average Value ◽  
Significant Difference ◽  
Fgf 23

Abstract Background and Aims Chronic kidney disease (CKD) is considered a global medical and public health issue. CKD takes a special place among non-infectious diseases because of its prevalence (6-20% according to different surveys and studies) and is associated with a poor life quality, complications and high risk of mortality. In recent years, there have been new biomarkers requiring more research in this area. One of these biomarkers is Fibroblast growth factor-23 (FGF-23) which is found as a bone derived hormone and might be a predictor of progression. However, the role of FGF-23 in CKD progression in children has not been adequately studied, especially on the early stages. Nowadays, the study of FGF-23 in children and the question of the clinical importance of this marker are relevant. Therefore, the aim of our study was to establish the role of FGF-23 in CKD progression in children. Method A prospective study was conducted on 73 children with different stages of CKD and 14 healthy individuals (control group) matched by age and gender. There were approximately equal numbers of patients in study groups. An average age was 9.61±1.05 years. Exclusion criteria: active inflammatory, bone, infectious, oncological, immunological diseases, taking steroids and vitamin D supplements. Laboratory measurements included all common clinical and biochemical indicators. Serum concentration of intact FGF-23 was assessed by using the ELISA method (Biomedica Medizinprodukte GmbH, Austria). Statistical analysis was conducted in MS Excel 2016 and SPSS 18.0. Results The normal range of FGF-23 for this kit was 0.1-1.5 pmol/l. The average value of FGF-23 in the control group was 0.69±0.12 pmol/l. Further studies in the groups with different stages of CKD revealed that FGF-23 concentration gradually rose in parallel with stages of CKD, and it reached the maximum on the last stage. It should be noticed that the level of FGF-23 concentration on the first stage of CKD was normal (0.73±0.14 pmol/l) and the comparison with healthy individuals revealed no significant differences. What is remarkable, despite the fact that the average value of the second stage patients was normal (1.36±0.2 pmol/l), there was a statistically significant difference with the control group (p=0.008). The levels of FGF-23 on the next stages were 2.52±0.52 pmol/l, 5.42±1.61 pmol/l, and 12.16±1.55 pmol/l, respectively. The differences were considerable and proved by statistical analysis (p&lt;0.01). Conclusion Our study showed that there is an upward trend of FGF-23 as CKD progresses from early to advanced stages. The results on the second and third stages indicate that FGF-23 should be considered as one of early biomarkers of CKD progression in children. Thus, there is a need for more studies in this area.

scholarly journals Role of vitamin D-binding protein in isocyanate-induced occupational asthma

2012 ◽  
Vol 44 (5) ◽  
pp. 319 ◽  
Author(s):  
Sung-Ho Kim ◽  
Gil-Soon Choi ◽  
Young-Hee Nam ◽  
Joo-Hee Kim ◽  
Gyu-Young Hur ◽  
...  
Keyword(s):  
Vitamin D ◽  
Occupational Asthma ◽  
Binding Protein ◽  
Vitamin D Binding Protein

scholarly journals Role of the vitamin D receptor in FGF23 action on phosphate metabolism

2005 ◽  
Vol 390 (1) ◽  
pp. 325-331 ◽  
Author(s):  
Yoshio Inoue ◽  
Hiroko Segawa ◽  
Ichiro Kaneko ◽  
Setsuko Yamanaka ◽  
Kenichiro Kusano ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Fibroblast Growth Factor 23 ◽  
Mrna Levels ◽  
Dna Encoding ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Naked Dna ◽  
25 Hydroxyvitamin D

FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(−/−) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(−/−) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1α-hydroxylase mRNA levels in VDR(−/−) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(−/−) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1α-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR.

scholarly journals Vitamin D Metabolism Is Significantly Impaired in COVID-19 Inpatients

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A281-A282
Author(s):  
Alexandra Povaliaeva ◽  
Liudmila Ya Rozhinskaya ◽  
Ekaterina A Pigarova ◽  
Larisa K Dzeranova ◽  
Nino N Katamadze ◽  
...  
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Deficiency ◽  
Serum Calcium ◽  
Vitamin D Supplementation ◽  
Vitamin D Metabolites ◽  
Lung Involvement ◽  
Hydroxylase Activity ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

Abstract Objective: to assess the state of vitamin D metabolism in patients hospitalized with COVID-19 infection. Materials and methods: We examined 49 patients, which were hospitalized for inpatient treatment of COVID-19 infection from May to June 2020. Study group included 24 men (49%) and 25 women (51%), median age 58 years [48; 70], BMI 26.4 kg/m2 [24.3; 30.5]. All patients were diagnosed with pneumonia due to SARS-CoV-2 with median percent of lung involvement equal to 29% [14; 37], 22 patients (45%) required oxygen support upon admission. Median SpO2 was equal to 95% (92; 97), median NEWS score was equal to 3 [2; 6]. Participants were tested for vitamin D metabolites (25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3 and D3) by UPLC-MS/MS, free 25(OH)D and vitamin D-binding protein by ELISA, as well as PTH by electrochemiluminescence immunoassay and routine biochemical parameters of blood serum (calcium, phosphorus, albumin) at the time of admission. Results: patients had in general very low 25()D3 levels - median 10.9 ng/mL [6.9; 15.6], corresponding to a pronounced vitamin D deficiency in half of the patients. Levels of 24,25(OH)2D3 were also low – 0.5 ng/mL [0.2; 0.9], and resulting vitamin D metabolite ratios (25(OH)D3/24,25(OH)2D3) were high-normal or elevated in most patients – 24.1 [19.0; 39.2], indicating decreased activity of 24-hydroxylase. Levels of 1,25(OH)2D3, on the contrary, were high-normal or elevated - 57 pg/mL [46; 79], which, in accordance with 25(OH)D3/1,25(OH)2D3 ratio (219 [134; 266]) suggests an increase in 1α-hydroxylase activity. Median level of 3-epi-25(OH)D3 was 0.7 ng/mL [0.4; 1.0] and D3 metabolite was detectable only in 6 patients. Median DBP level was 432 mg/L [382; 498], median free 25(OH)D was 5.6 pg/mL [3.3; 6.7], median calculated free 25(OH)D was 2.0 pg/mL [1.4; 3.3]. Most patients had albumin-adjusted serum calcium level in the lower half of reference range (median 2.24 mmol/L [2.14; 2.34]). Seven patients had secondary hyperparathyroidism and one patient had primary hyperparathyroidism, the rest of the patients had PTH levels within the normal range.25(OH)D3 levels showed significant negative correlation with percent of lung involvement (r = -0.36, p&lt;0.05) and positive correlation with SpO2 (r = 0.4, p&lt;0.05). 1,25(OH)2D3 levels correlated positively with 25(OH)D3 levels (r = 0.38, p&lt;0.05) and did not correlate significantly with PTH levels (p&gt;0.05). Conclusion: Our data suggests that hospitalized patients with COVID-19 infection have significant impairment of vitamin D metabolism, in particular, an increase in 1α-hydroxylase activity, which cannot be fully explained by pre-existing conditions such as vitamin D deficiency and secondary hyperparathyroidism. The observed profound vitamin D deficiency and association of vitamin D levels with markers of disease severity indicate the importance of vitamin D supplementation in these patients.

scholarly journals Role of Fibroblast Growth Factor- 23 in Coronary Artery Diseases and its Association with Apolipoprotein A1

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Fadhil Jawad Al-Tu'ma ◽  
Anaam Hato Kadhim ◽  
Anaam Hato Kadhim ◽  
Saif Sami Al-Mudhaffar
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Apolipoprotein A1 ◽  
Control Group ◽  
Significant Difference ◽  
Artery Disease ◽  
Fgf 23

Coronary artery disease (CAD) is a clinical manifestation resulting from a narrowing of epicardial coronary arteries that supply blood and oxygen to the heart. Coronary artery disease is mostcommonlydue to atherosclerotic occlusion of the coronary arteries.Fibroblast growth factor 23 (FGF23) is a circulating peptide hormone secreted by bone cells,regulating phosphate and vitamin D metabolism. Several recent observational studies reported an independent association of circulating FGF23 with several cardiovascular disease (CVD) risk factors including left ventricular hypertrophy and vascular dysfunction,CVD progression and incident clinical CVD eventsand mortality.Apolipoprotein A1 (ApoA1) is the primary protein associated with high-density lipoprotein (HDL) particles,and plays a central role in reverse cholesterol transport. HDL cholesterol (HDL-C) and ApoA1 concentrations are inverlassely related to the risk for coronary artery disease. To find the role of fibroblast growth factor-23 in coronary artery disease and its associationwith Apolipoprotein-A1.This ccross –sectionalstudyincluded 42 elective patients attending the cardiology unit and the results of those patients were compared with 40 healthy control group. Blood samples were obtained for measurements of (FGF-23,troponin I,Apo-A1,total creatine kinase activity,urea,creatinine and lipid profile).The obtained results showed that there was a significant difference in serum FGF-23 in coronary artery disease (367.52 ± 128.52 pg/ml) as compared with the control (165.41 ± 53.65 pg/ml) (p< 0.05). There was a significant differences in Apo-A1 in coronary artery disease (2.03±0.90 mg/ml) as compared with the control (1.49 ± 0.25 mg/ml) (P = 0.014).There was a significant difference in age between CAD (58.66±8.85) and control group (51.125 ± 11.71) (P<0.005).There was a significant difference in TG where control (99.50 ± 21.59) differ from CAD (142.05 ± 66.24) (P = 0.006).According to the results that were shown in the tables, we can be conclude that higher levels of FGF23 and Apo-A1 may be associated with complications and mortality of CAD beside its associating with atherosclerosis in the Iraqi patients.

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