Renal phosphate transporters

Lederer, Eleanor

doi:10.1097/mnh.0000000000000053

Cited by 30 publications

(33 citation statements)

References 25 publications

(20 reference statements)

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“…In humans, mutations in Npt2c lead to hereditary hypophosphataemic rickets with hypercalciuria (HHRH) compared with mutations in Npt2a, which are characterised by the development of nephrocalcinosis and increased osteoporotic risk. These findings support the importance of the Npt2c cotransporter in human phosphate balance [28,32,33].…”

Section: Renal Handling Of Phosphatesupporting

confidence: 82%

Calcium, Phosphate and Magnesium Disorders

Heron¹

2019

Fluid and Electrolyte Disorders

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Calcium, phosphate and magnesium are essential for human function and life. Each electrolyte is readily found in the human diet, and homeostasis is tightly regulated by the intestine, kidney and bone as well as other critical hormones, receptors and transporters. Disturbance to this balance can result in symptomatic disease and life-threatening manifestations. Calcium and phosphate are particularly co-dependent with disruption to the balance of one often influencing the other. It is important that clinicians have a thorough understanding of the mechanisms underplaying the homeostasis of each electrolyte as they have implications for prevention and management of disease. This chapter aims to outline the importance of calcium, phosphate and magnesium; the regulation of each electrolyte and the consequences of imbalance.

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Section: Renal Handling Of Phosphatesupporting

confidence: 82%

Calcium, Phosphate and Magnesium Disorders

Heron¹

2019

Fluid and Electrolyte Disorders

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“…SLC20A2 protein lines the apical (ventricular lumen) side of the ependymal cells (illustrated in red in Figure A), and thus was exquisitely poised to participate in ventricular phosphate re‐uptake from the ventricles to the interstitium. Analogous to the role of type II transporters in controlling urinary phosphate levels, SLC20A2 appears to be a major determinant of CSF phosphate levels .…”

Section: Resultsmentioning

confidence: 99%

SLC20A2 Deficiency in Mice Leads to Elevated Phosphate Levels in Cerbrospinal Fluid and Glymphatic Pathway‐Associated Arteriolar Calcification, and Recapitulates Human Idiopathic Basal Ganglia Calcification

et al. 2016

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Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification.

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“…Unlike other minerals such as calcium, magnesium, potassium, sodium, or chloride, the endocrine regulation of phosphate reabsorption in the kidney takes place in the proximal renal tubule, and involves the regulation of the luminal membrane abundance of phosphatetransporting molecules in the epithelium [22]. Parathyroid hormone (PTH), the principal phosphaturic hormone, downregulates membrane expression of the key sodium-phosphate cotransporter, NaPi-2a, by a signaling cascade leading to phosphorylation of Na + /H + exchange regulatory cofactor (NHERF)-1 as a final step.…”

Section: Proximal Tubular Phosphate Re-uptakementioning

confidence: 99%

FGF23-Klotho signaling axis in the kidney

Erben

Andrukhova

2017

Bone

132

110

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Fibroblast growth factor-23 (FGF23) is a bone-derived hormone protecting against the potentially deleterious effects of hyperphosphatemia by suppression of phosphate reabsorption and of active vitamin D hormone synthesis in the kidney. The kidney is one of the main target organs of FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23-Klotho signaling in the kidney. During recent years, it has become clear that FGF23 acts independently on proximal and distal tubular epithelium. In proximal renal tubules, FGF23 suppresses phosphate reabsorption by a Klotho dependent activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and of serum/glucocorticoid-regulated kinase-1 (SGK1), leading to phosphorylation of the scaffolding protein Na/H exchange regulatory cofactor (NHERF)-1 and subsequent internalization and degradation of sodium-phosphate cotransporters. In distal renal tubules, FGF23 augments calcium and sodium reabsorption by increasing the apical membrane expression of the epithelial calcium channel TRPV5 and of the sodium-chloride cotransporter NCC through a Klotho dependent activation of with-no-lysine kinase-4 (WNK4). In proximal and distal renal tubules, FGF receptor-1 is probably the dominant FGF receptor mediating the effects of FGF23 by forming a complex with membrane-bound Klotho in the basolateral membrane. The newly described sodium- and calcium-conserving functions of FGF23 may have major implications for the pathophysiology of diseases characterized by chronically increased circulating FGF23 concentrations such as chronic kidney disease.

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Renal phosphate transporters

Abstract: http://links.lww.com/CONH/A10.

Cited by 30 publications

References 25 publications

Calcium, Phosphate and Magnesium Disorders

Calcium, Phosphate and Magnesium Disorders

SLC20A2 Deficiency in Mice Leads to Elevated Phosphate Levels in Cerbrospinal Fluid and Glymphatic Pathway‐Associated Arteriolar Calcification, and Recapitulates Human Idiopathic Basal Ganglia Calcification

FGF23-Klotho signaling axis in the kidney

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