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Review
. 2011 Feb;120(3):91-7.
doi: 10.1042/CS20100377.

Phosphate toxicity: new insights into an old problem

M Shawkat Razzaque  1
Affiliations
Review

Phosphate toxicity: new insights into an old problem

M Shawkat Razzaque. Clin Sci (Lond). 2011 Feb.

Abstract

Phosphorus is an essential nutrient required for critical biological reactions that maintain the normal homoeostatic control of the cell. This element is an important component of different cellular structures, including nucleic acids and cell membranes. Adequate phosphorus balance is vital for maintaining basic cellular functions, ranging from energy metabolism to cell signalling. In addition, many intracellular pathways utilize phosphate ions for important cellular reactions; therefore, homoeostatic control of phosphate is one of the most delicate biological regulations. Impaired phosphorus balance can affect the functionality of almost every human system, including musculoskeletal and cardiovascular systems, ultimately leading to an increase in morbidity and mortality of the affected patients. Human and experimental studies have found that delicate balance among circulating factors, like vitamin D, PTH (parathyroid hormone) and FGF23 (fibroblast growth factor 23), are essential for regulation of physiological phosphate balance. Dysregulation of these factors, either alone or in combination, can induce phosphorus imbalance. Recent studies have shown that suppression of the FGF23-klotho system can lead to hyperphosphataemia with extensive tissue damage caused by phosphate toxicity. The cause and consequences of phosphate toxicity will be briefly summarized in the present review.

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Figures

Figure 1
Figure 1. Simplified diagram showing muti-organ interactions in regulation of phosphate homoeostasis
FGF23 produced in the bone cells can suppress renal NaPi-2a and NaPi-2c co-transporter activities to increase the urinary excretion of phosphate. Likewise, FGF23 can also suppress renal expression of 1α(OH)ase to reduce production of 1,25(OH)2D (1,25-dihydroxyvitamin D), which can suppress intestinal NaPi-2b activities to reduce phosphate absorption, resulting in decreased serum phosphate levels [6].
Figure 2
Figure 2. Partial list of pathological events related to phosphate toxicity as documented in both human and animal studies
Summarized from [40,66,67,72,78,79].
See this image and copyright information in PMC

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