Coupling between phosphate and calcium homeostasis: a mathematical model

2017 ◽  
Vol 313 (6) ◽  
pp. F1181-F1199 ◽  
Author(s):  
David Granjon ◽  
Olivier Bonny ◽  
Aurélie Edwards
Keyword(s):  
Mathematical Model ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Production Rate ◽  
Fibroblast Growth Factor 23 ◽  
Feedback Loops ◽  
Fibroblast Growth ◽  
Small Perturbations ◽  
Intracellular Pool ◽  
Negative Feedback Loops

We developed a mathematical model of calcium (Ca) and phosphate (PO4) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO4balance. The model represents the exchanges of Ca and PO4between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO4-fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D3, fibroblast growth factor 23, and Ca2+-sensing receptors. Our results suggest that the Ca and PO4homeostatic systems are robust enough to handle small perturbations in the production rate of either PTH or vitamin D3. The model predicts that large perturbations in PTH or vitamin D3synthesis have a greater impact on the plasma concentration of Ca2+([Ca2+]p) than on that of PO4([PO4]p); due to negative feedback loops, [PO4]pdoes not consistently increase when the production rate of PTH or vitamin D3is decreased. Our results also suggest that, following a large PO4infusion, the rapidly exchangeable pool in bone acts as a fast, transient storage PO4compartment (on the order of minutes), whereas the intracellular pool is able to store greater amounts of PO4over several hours. Moreover, a large PO4infusion rapidly lowers [Ca2+]powing to the formation of CaPO4complexes. A large Ca infusion, however, has a small impact on [PO4]p, since a significant fraction of Ca binds to albumin. This mathematical model is the first to include all major regulatory factors of Ca and PO4homeostasis.

scholarly journals Vitamin D and the Immune System from the Nephrologist's Viewpoint

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Cheng-Lin Lang ◽  
Min-Hui Wang ◽  
Chih-Kang Chiang ◽  
Kuo-Cheng Lu
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Immune System ◽  
Kidney Diseases ◽  
Fibroblast Growth Factor 23 ◽  
Clinical Use ◽  
Fibroblast Growth ◽  
Immunomodulatory Effects ◽  
The Relationship

Vitamin D and its analogues are widely used as treatments by clinical nephrologists, especially when treating chronic kidney disease (CKD) patients with secondary hyperparathyroidism. As CKD progresses, the ability to compensate for elevations in parathyroid hormone (PTH) and fibroblast growth factor-23 and for decreases in 1,25(OH)2D3 becomes inadequate, which results in hyperphosphatemia, abnormal bone disorders, and extra-skeletal calcification. In addition to its calciotropic effect on the regulation of calcium, phosphate, and parathyroid hormone, vitamin D has many other noncalciotropic effects, including controlling cell differentiation/proliferation and having immunomodulatory effects. There are several immune dysregulations that can be noted when renal function declines. Physicians need to know well both the classical and nonclassical functions of vitamin D. This review is an analysis from the nephrologist's viewpoint and focuses on the relationship between the vitamin D and the immune system, together with vitamin's clinical use to treat kidney diseases.

scholarly journals 25-vitamin D, 1,25-vitamin D, parathyroid hormone, fibroblast growth factor-23 and cognitive function in men with advanced CKD: a veteran population

2014 ◽  
Vol 82 (2014) (11) ◽  
pp. 296-303 ◽  
Author(s):  
Anna J. Jovanovich ◽  
Michel Chonchol ◽  
Christopher B. Brady ◽  
James D. Kaufman ◽  
Jessica Kendrick ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Cognitive Function ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth

scholarly journals FGF23 as a calciotropic hormone

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1472 ◽  
Author(s):  
María E. Rodríguez-Ortiz ◽  
Mariano Rodríguez
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Calcium Homeostasis ◽  
Bone Cells ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Calcium Deficiency ◽  
Fibroblast Growth

Maintaining mineral metabolism requires several organs and hormones. Fibroblast growth factor 23 (FGF23) is a phosphatonin produced by bone cells that reduces renal production of calcitriol – 1,25(OH)2D3 – and induces phosphaturia. The consequences of a reduction in 1,25(OH)2D3 involve changes in calcium homeostasis. There are several factors that regulate FGF23: phosphorus, vitamin D, and parathyroid hormone (PTH). More recently, several studies have demonstrated that calcium also modulates FGF23 production. In a situation of calcium deficiency, the presence of 1,25(OH)2D3 is necessary to optimize intestinal absorption of calcium, and FGF23 is decreased to avoid a reduction in 1,25(OH)2D3 levels.

scholarly journals The impact of vitamin D status on the relative increase in fibroblast growth factor 23 and parathyroid hormone in chronic kidney disease

2014 ◽  
Vol 86 (2) ◽  
pp. 407-413 ◽  
Author(s):  
Maarten W. Taal ◽  
Victoria Thurston ◽  
Natasha J. McIntyre ◽  
Richard J. Fluck ◽  
Christopher W. McIntyre
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Relative Increase ◽  
Fibroblast Growth ◽  
Vitamin D Status ◽  
The Impact

scholarly journals Fibroblast growth factor-23 regulates parathyroid hormone and 1α-hydroxylase expression in cultured bovine parathyroid cells

2007 ◽  
Vol 195 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Tijana Krajisnik ◽  
Peyman Björklund ◽  
Richard Marsell ◽  
Östen Ljunggren ◽  
Göran Åkerström ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Mrna Level ◽  
Serum Levels ◽  
Negative Regulator ◽  
Fibroblast Growth

Fibroblast growth factor-23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate (Pi) as well as 1,25-dihydroxyvitamin D3. Recent studies also suggest a correlation between serum levels of FGF23 and parathyroid hormone (PTH) in patients with chronic kidney disease. It is, however, unknown whether FGF23 directly modulates PTH expression, or whether the correlation is secondary to abnormalities in Pi and vitamin D metabolism. The objective of the current study was therefore to elucidate possible direct effects of FGF23 on bovine parathyroid cells in vitro. Treatment of parathyroid cells with a stabilized form of recombinant FGF23 (FGF23(R176Q)) induced a rise in early response gene-1 mRNA transcripts, a marker of FGF23 signaling. FGF23(R176Q) potently and dose-dependently decreased the PTH mRNA level within 12 h. In agreement, FGF23(R176Q) also decreased PTH secretion into conditioned media. In contrast, FGF23(R176Q) dose-dependently increased 1α-hydroxylase expression within 3 h. FGF23 (R176Q) did not affect cell viability nor induce apoptosis, whereas a small but significant increase in cell proliferation was found. We conclude that FGF23 is a negative regulator of PTH mRNA expression and secretion in vitro. Our data suggest that FGF23 may be a physiologically relevant regulator of PTH. This defines a novel function of FGF23 in addition to the previously established roles in controlling vitamin D and Pi metabolism.

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