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Abstract
Calcium (Ca2+) and phosphate (Pi) are essential to many vital physiological processes. Consequently the maintenance of Ca2+ and Pi homeostasis is essential to a healthy existence. This occurs through the concerted action of intestinal, renal, and skeletal regulatory mechanisms. Ca2+ and Pi handling by these organs is under tight hormonal control. Disturbances in their homeostasis have been linked to pathophysiological disorders including chronic renal insufficiency, kidney stone formation, and bone abnormalities. Importantly, the kidneys fine‐tune the amount of Ca2+ and Pi retained in the body by altering their (re)absorption from the glomerular filtrate. The ion transport proteins involved in this process have been studied extensively. Recently, new key players have been identified in the regulation of the Ca2+ and Pi balance. Novel regulatory mechanisms and their implications were introduced for the antiaging hormone klotho and fibroblast growth factor member 23 (FGF23). Importantly, transgenic mouse models, exhibiting disturbances in Ca2+ and Pi balance, have been of great value in the elucidation of klotho and FGF23 functioning. This review highlights the current knowledge and ongoing research into Ca2+ and Pi homeostasis, emphasizing findings from several relevant knockout mouse models.
Acknowledgements
This work was financially supported in part by grants from the Dutch Kidney Foundation (C03.6017 and C06.2170), the Netherlands Organization for Scientific Research (Zon‐Mw 016.006.001, NWO‐ALW 814.02.001, NWO‐CW 700.55.302), and the Dutch Stomach‐Intestine‐Liver foundation (MWO 03‐19). J. Hoenderop and R. T. Alexander are supported by an EURYI and a CIHR Clinician‐Scientist award, respectively. We thank the members of our laboratory for valuable discussion and advice.