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Physiology of the Developing Kidney: Disorders and Therapy of Calcium and Phosphorous Homeostasis

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Pediatric Nephrology

Abstract

The regulation of calcium and phosphate homeostasis involves several different hormones that act on the kidney, intestine, and bone. The most important calcium-regulating peptide hormone is parathyroid hormone (PTH). Its production and secretion by the parathyroid glands increases in response to a decrease in the extracellular calcium concentration. PTH increases (1) the 1α-hydroxylase activity in the proximal renal tubules to promote production of the biologically active 1,25-dihydroxyvitamin D (1,25(OH)2D) from its precursor 25-hydroxyvitamin D, thereby enhancing intestinal absorption of calcium (and phosphorus); (2) it stimulates bone resorption, thus releasing calcium and (phosphorus); (3) it enhances calcium reabsorption in the distal renal tubules; and (4) it promotes urinary phosphate excretion. These phosphaturic actions of PTH occur within minutes by reducing the expression of two sodium-dependent phosphate cotransporters, NPT2a and NPT2c, in the proximal convoluted tubules. The long-term regulation of phosphate homeostasis involves fibroblast growth factor 23 (FGF23), a more recently discovered hormone made by osteocytes and probably osteoblasts. Like PTH, FGF23 reduces the expression of NPT2a and NPT2c, but the time courses for the effects of both hormones are very different [1–3]. Furthermore, in contrast to the stimulatory actions of PTH on 1α-hydroxylase, FGF23 reduces the expression of this enzyme in the proximal renal tubules, and it enhances 24-hydroxylase, leading to two different mechanisms to a reduction in serum 1, 25(OH)2D levels [4–8].

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Sharma, A., Thakker, R.V., Jüppner, H. (2014). Physiology of the Developing Kidney: Disorders and Therapy of Calcium and Phosphorous Homeostasis. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N., Emma, F., Goldstein, S. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27843-3_10-1

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