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Phosphatonins – Basic Science and Clinical Aspects

Rajiv Kumar

Mayo Clinic and Foundation, Rochester, Minnesota, USA
MAY 11th - Symposium 1 - HALL A4/5 08:00 - 09:30

A variety factors regulate the efficiency of phosphate absorption in the intestine and phosphate reabsorption in kidney. 
Apart from the well-known regulators of phosphate homeostasis, namely, parathyroid hormone and the vitamin D-endocrine system, a number of peptides collectively known as the “phosphatonins” have been recently identified as a result of the study of various diseases associated with hypophosphatemia. 
PTH regulates phosphate in the kidney by decreasing proximal tubular phosphate reabsorption, and it indirectly influences phosphate homeostasis by regulating the synthesis of 1, 25-dihydroxyvitamin D, which, in turn, increases the efficiency of phosphate absorption in the intestine.  The phosphatonins --  fibroblast growth factor 23 (FGF-23), secreted frizzled related protein 4 (sFRP-4), fibroblast growth factor 7(FGF-7) and matrix extracellular phosphoglycoprotein (MEPE) have been shown to play a role in the pathogenesis of various hypophosphatemic and hyperphosphatemic disorders such as oncogenic osteomalacia, X-link hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemia and tumoral calcinosis. 
A co-receptor for FGF23, namely, klotho, also appears to modulate renal phosphate reabsorption.  The inactivating mutations of the klotho gene are associated with tumoral calcinosis, and recently, a translocation of the klotho gene has been associated with hypophosphatemia and hyperparathyroidism.  Whether the phosphatonins are true hormones, in the sense that they are regulated by the intake of dietary phosphorus and the needs of the organism for higher or lower amounts of phosphorus, remains to be firmly established in humans. 
Most data shows that the short-term regulation of renal phosphate excretion is not mediated by the phosphatonins.  New information demonstrates that the intestine “senses” luminal concentrations of phosphate and regulates the excretion of phosphate in the kidney by elaborating novel factors that alter renal phosphate reabsorption.