Molecular Mechanisms of Adverse Health Effects Associated With Excess Phosphorus Intake

Jaime Uribarri, Mona S. Calvo

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Excess phosphorus intake has always been a concern in patients with chronic kidney disease because of their impaired ability to excrete phosphorus loads and the known association between excess phosphorus and health complications, including cardiovascular disease, in this population. More recently, large epidemiological studies suggest that mild elevations of serum phosphate still within the normal range are associated with cardiovascular disease risk in healthy populations without evidence of kidney disease. In healthy adults with functional kidneys, phosphorus balance is achieved when serum concentrations are maintained in a very narrow range, which requires a sustained balance between urinary loss and net phosphorus absorption from the gastrointestinal tract. This balance is carried out through a complex organ network, the bone-kidney-intestine network, which operates through complex, ordered endocrine negative feedback loops involving parathyroid hormone, fibroblast growth factor-23, Klotho, and vitamin D and several tissue-specific cellular phosphate transporters. Disruption of this ordered endocrine regulation has been shown to result in the type of tissue damage associated with some chronic disease risks. Excess phosphorus consumption, well beyond the level of required nutrient intake, is a key suspect in the possible disruption of the endocrine regulation of phosphorus balance and may be associated with chronic disease risk in adults with normal renal function. The increased cumulative use of phosphorus ingredients in food processing in modern society together with our increasing knowledge about new endocrine pathways that may connect phosphorus intake and pathology raises the issue of the potential toxicity of an essential mineral such as phosphorus when taken in excess. This chapter summarizes what is currently known about phosphate homeostasis, the mechanisms involved in its regulation, and related pathologies in patients with chronic kidney disease as well as in the general population.

Original languageEnglish
Title of host publicationMolecular, Genetic, and Nutritional Aspects of Major and Trace Minerals
PublisherElsevier Inc.
Pages429-436
Number of pages8
ISBN (Electronic)9780128023761
ISBN (Print)9780128021682
DOIs
StatePublished - 2017

Keywords

  • Bone loss
  • Calcium-to-phosphate intake ratio
  • Cancer
  • Cardiovascular disease (CVD)
  • Chronic kidney disease (CKD)
  • Dietary phosphorus intake
  • Fibroblast growth factor-23 (FGF23)
  • Klotho
  • Parathyroid hormone (PTH)
  • Phosphate food additives
  • Phosphorus homeostasis
  • Sodium phosphate cotransporters (NaPi-IIb and others)

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