A model of calcium homeostasis in the rat

Granjon, David; Bonny, Olivier; Edwards, Aurélie

doi:10.1152/ajprenal.00230.2016

Cited by 15 publications

(14 citation statements)

References 95 publications

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“…Calcium concentration is predicted to be extremely high at the tip of the renal papilla, especially around vasa recta [60,61]. Considering (i) that phosphate concentration is certainly significant, although reabsorbed partly in the proximal tubule, and (ii) that papillary pH should stand within physiological range (7.4), calcium phosphate supersaturation should be extremely high at the tip of the papilla.…”

Section: Randall's Plaque and Calcification Inhibitorsmentioning

confidence: 99%

Pseudoxanthoma Elasticum, Kidney Stones and Pyrophosphate: From a Rare Disease to Urolithiasis and Vascular Calcifications

Letavernier

Bouderlique

Martin

et al. 2019

IJMS

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Pseudoxanthoma elasticum is a rare disease mainly due to ABCC6 gene mutations and characterized by ectopic biomineralization and fragmentation of elastic fibers resulting in skin, cardiovascular and retinal calcifications. It has been recently described that pyrophosphate (a calcification inhibitor) deficiency could be the main cause of ectopic calcifications in this disease and in other genetic disorders associated to mutations of ENPP1 or CD73. Patients affected by Pseudoxanthoma Elasticum seem also prone to develop kidney stones originating from papillary calcifications named Randall’s plaque, and to a lesser extent may be affected by nephrocalcinosis. In this narrative review, we summarize some recent discoveries relative to the pathophysiology of this mendelian disease responsible for both cardiovascular and renal papillary calcifications, and we discuss the potential implications of pyrophosphate deficiency as a promoter of vascular calcifications in kidney stone formers and in patients affected by chronic kidney disease.

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Section: Randall's Plaque and Calcification Inhibitorsmentioning

confidence: 99%

Pseudoxanthoma Elasticum, Kidney Stones and Pyrophosphate: From a Rare Disease to Urolithiasis and Vascular Calcifications

Letavernier

Bouderlique

Martin

et al. 2019

IJMS

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“…Using the experimental approach previously described [32], we measured the amount of bone PO 4 in C57BL/6 male and female mice (weighing ∼20g) and extrapolated our results to rats.…”

Section: Resultsmentioning

confidence: 99%

“…In plasma, about 50% of Ca is bound to proteins, albumin being the dominant ligand (46-55%) [7,88]. We previously assumed that the fraction (κ b ) of Ca bound to proteins such as albumin remains constant [32]. In the present model, we explicitly take into account the dynamic binding of Ca 2+ to albumin.…”

Section: Ca Homeostasismentioning

confidence: 99%

“…Given the coupling between the homeostasis of calcium and that of phosphate, the values of several calcium-related parameters described in our previous model [32] had to be adjusted.…”

Section: Conservation Equation For Plasma Calciummentioning

confidence: 99%

“…The homeostatic regulation of PO 4 is tightly coupled to that of Ca. In the present study, we expanded the calcium homeostasis model that we previously built [32] to include phosphate and to examine the impact of hormonal dysfunctions on PO 4 and Ca balance.…”

Section: Introductionmentioning

confidence: 99%

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Coupling between phosphate and calcium homeostasis: a mathematical model

Granjon

Bonny

Edwards

2017

American Journal of Physiology-Renal Physiology

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

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