Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity

Abstract

Phosphate homeostasis is coordinated and regulated by complex cross-organ talk through delicate hormonal networks. Parathyroid hormone (PTH), secreted in response to low serum calcium, has an important role in maintaining phosphate homeostasis by influencing renal synthesis of 1,25-dihydroxyvitamin D, thereby increasing intestinal phosphate absorption. Moreover, PTH can increase phosphate efflux from bone and contribute to renal phosphate homeostasis through phosphaturic effects. In addition, PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), which is able to inhibit renal tubular phosphate reabsorption, thereby increasing urinary phosphate excretion. FGF23 can also fine-tune vitamin D homeostasis by suppressing renal expression of 1-alpha hydroxylase (1a(OH)ase). This review briefly discusses how FGF23, by forming a bone-kidney axis, regulates phosphate homeostasis, and how its dysregulation can lead to phosphate toxicity that induces widespread tissue injury. We also provide evidence to explain how phosphate toxicity related to dietary phosphorus overload may facilitate incidence of noncommunicable diseases including kidney disease, cardiovascular disease, cancers and skeletal disorders.

The biochemistry of saliva throughout pregnancy

“…38 These inverted proportional calcium/phosphate saliva concentrations may be justified by phosphate homeostasis, where the secretion of parathyroid hormone in response to low serum calcium can increase phosphate efflux from bone, kidney and gastrointestinal tract. 40 Pregnancy does not seem to alter salivary chloride levels and in this respect our results are concordant with a previous report by Guidozzi et al 22 This result is in agreement with the fact that plasma chloride levels are not altered during pregnancy. 1 Regarding salivary potassium levels, we found that pregnant women did not differ from non-pregnant women, whereas results from Guidozzi and colleagues 22 showed lower salivary potassium levels in saliva of women in the third trimester of pregnancy.…”

Vitamin D: Classic and Novel Actions

“…Under low serum calcium conditions, or low levels of vitamin D, PTH secreted by the parathyroid glands stimulates the synthesis of the 1α-hydroxylase, resulting in the increase of 1,25(OH) 2 D activation [11]. PTH also inhibits 24-hydroxylase [12], and can induce osteoclast and osteocytes synthesis of the FGF-23, which acts by reducing the expression of renal sodium-phosphate transporters [13]. FGF-23 can also adjust vitamin D homeostasis by suppressing renal expression of 1α-hydroxylase and inducing 24-hydroxylase, thus reducing serum calcitriol levels and subsequently serum calcium under hyperphosphatemia conditions [14].…”

Vitamin D, phosphate, and vasculotoxicity

“…should be a therapeutic priority in CKD patients to minimize the risk of developing vascular mineralization and associated complications (Brown and Razzaque 2015). Table 1 Partial list of known inducers and inhibitors of vascular calcification.…”