Phosphate—a poison for humans?

Abstract

Maintenance of phosphate balance is essential for life, and mammals have developed a sophisticated system to regulate phosphate homeostasis over the course of evolution. However, due to the dependence of phosphate elimination on the kidney, humans with decreased kidney function are likely to be in a positive phosphate balance. Phosphate excess has been well recognized as a critical factor in the pathogenesis of mineral and bone disorders associated with chronic kidney disease, but recent investigations have also uncovered toxic effects of phosphate on the cardiovascular system and the aging process. Compelling evidence also suggests that increased fibroblastic growth factor 23 and parathyroid hormone levels in response to a positive phosphate balance contribute to adverse clinical outcomes. These insights support the current practice of managing serum phosphate in patients with advanced chronic kidney disease, although definitive evidence of these effects is lacking. Given the potential toxicity of excess phosphate, the general population may also be viewed as a target for phosphate management. However, the widespread implementation of dietary phosphate intervention in the general population may not be warranted due to the limited impact of increased phosphate intake on mineral metabolism and clinical outcomes. Nonetheless, the increasing incidence of kidney disease or injury in our aging society emphasizes the potential importance of this issue. Further work is needed to more completely characterize phosphate toxicity and to establish the optimal therapeutic strategy for managing phosphate in patients with chronic kidney disease and in the general population.

The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis

“…Thus, P i homeostasis is essential to life, but the mechanisms by which this occurs in humans and other metazoans are largely unknown (1,2). Most of the previous work in this field of research has focused on yeast models (3)(4)(5).…”

“…The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 1 Supported by Swiss National Science Foundation Grant PP00P2_157607. 2 Partially supported by National Center for Advancing Translational Sciences, National Institutes of Health Grant UL1TR001111.…”

The future of dialysis treatment: wearable artificial kidneys (WAKs)

“…In addition, a rise in the phosphate levels of some patients was noted. This is of importance because hyperphosphatemia is a marker of poor prognosis in ESRD patients [12]. Regardless, patients reported overall higher levels of treatment satisfaction and no major adverse events were reported.…”

Health implications of inorganic phosphate additives in food products: a systematic review

“…19 Given the increasing incidence of chronic diseases associated with phosphate additives, a study concludes that lack of adequate intervention and strict regulation may increase the burden of associated chronic diseases. 20 Evidence suggests that serum phosphate levels may not represent accurate amount of phosphate uptake by individuals, hence the difficulty in assessing actual amount of phosphate intake and increased susceptibility to hyperphosphatemia. 21 This report gives credence to the importance of advancing strategies to minimise the use of phosphate additives.…”