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Figure 1. Pi homeostasis. GI: Gastrointestinal; Pi: Phosphorus.
(Figure omitted. See article PDF.)
Figure 2. The pathophysiology of disorders of phosphate homeostasis. ADHR: Autosomal dominant hypophosphatemic rickets; ARHR: Autosomal recessive hypophosphatemia rickets; MEPE: Matrix extracellular phospoglycoprotein; Pi: Phosphorus; TC: Tumoral calcinosis; TIO: Tumor-induced osteomalacia; XLH: X-linked hypophosphatemic rickets/osteomalacia.
(Figure omitted. See article PDF.)
Phosphorus (Pi) homeostasis is controlled by numerous endocrine factors that exert effects on the intestine, kidney and bone to maintain physiological balance. Apart from parathyroid hormone (PTH) and the vitamin D endocrine system, a number of phosphaturic peptides, known as 'phosphatonins', which are involved in the pathogenesis of hypo- and hyperphosphatemic disorders, have been identified. All these factors, FGF-23, FGF-7, secreted frizzled-related protein (sFRP)-4, and matrix extracellular phosphoglycoprotein (MEPE) inhibit Na/Pi transporters in renal epithelial cells, increasing renal Pi excretion. Conversely, only FGF-23 and sFRP-4 inhibit 25-hydroxyvitamin D 1α-hydroxylase activity, reducing 1α,25(OH) 2 D3 synthesis and, thus, intestinal Pi absorption. This review describes the role of the phosphatonins in Pi homeostasis in normal and pathologic conditions.
Biological role of Pi
Phosphorus represents the sixth most abundant chemical element in the human body and is an important component of bone mineralization, fundamental for the formation of the hydroxyapatite crystal in cortical and trabecular bone. In addition, Pi plays an important role in nucleic acid synthesis, energy metabolism, membrane function, cell signaling and regulation of biochemical processes via phosphorylation/dephosphorylation [1]. Finally, Pi is also present in carbohydrates, membrane phospholipids and phosphoproteins, and is required for optimal cell growth [1].
As a result of these functions, chronic Pi deprivation causes several biological alterations, such as bone demineralization with unmineralized osteoid typical of osteomalacia in adults and rickets in developing animals and humans. Moreover, acute Pi deficiency can cause cardiac dysfunction, myopathy, alteration of platelets and neutrophil functions and red blood cell fragility [2].
On the other hand, hyperphosphatemia is a universal complication of chronic kidney diseases (CKDs) with a consequent reduction of circulating calcium levels and secondary hyperparathyroidism, the recognized basis of uremic osteodystrophy. When elevated serum phosphate is accompanied by circulating Ca, excess vascular calcifications occur with consequent increased arterial stiffness and left ventricular hypertrophy.
Pi homeostasis in humans
The normal plasma Pi concentration in an adult body is 15-20 mol (2.5-4.5...