Pediatr Nephrol (2008) 23:1203–1210 DOI 10.1007/s00467-008-0751-z REVIEW Regulation of phosphate homeostasis by the phosphatonins and other novel mediators Aisha Shaikh & Theresa Berndt & Rajiv Kumar Received: 11 October 2007 / Revised: 29 November 2007 / Accepted: 3 December 2007 / Published online: 21 February 2008 # IPNA 2008 Abstract A variety of factors regulate the efficiency of phosphate absorption in the intestine and phosphate reabsorption in kidney. Apart from the well-known regu- lators of phosphate homeostasis, namely parathyroid hor- mone (PTH) and the vitamin D–endocrine system, a number of peptides collectively known as the “phosphato- nins” have been recently identified as a result of the study of various diseases associated with hypophosphatemia. These factors, fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein 4 (sFRP-4), fibroblast growth factor 7 (FGF-7) and matrix extracellular phospho- glycoprotein (MEPE), have been shown to play a role in the pathogenesis of various hypophosphatemic and hyperphos- phatemic disorders, such as oncogenic osteomalacia, X- linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophos- phatemia and tumoral calcinosis. Whether these factors 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. Additionally, new informa- A. Shaikh : T. Berndt : R. Kumar (*) Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905, USA e-mail: rkumar@mayo.edu T. Berndt Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, Rochester, MN, USA R. Kumar Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN, USA tion 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. Keywords Phosphate . Vitamin D . Phosphatonins . PTH . Fibroblast growth factors Phosphorus homeostasis Phosphorus distribution: Phosphorus plays a critical role in many biological processes, including energy metabolism, cellular signaling through the phosphorylation of proteins and other substances, nucleic acid metabolism, membrane integrity, and bone mineralization. In the male human adult, total body phosphorus is between 15 mol and 20 mol (12.0 g/kg), the majority of which (80–90%) is present in bone in the form of hydroxyapatite [1, 2]. The remainder is present in soft tissues, extracellular fluid and erythrocytes. Soft tissue phosphorus is between 0.1% and 0.3% wet weight tissue (∼59 mmol/kg wet weight muscle). In plasma or serum, phosphorus exists as inorganic phosphate, lipid phosphorus and phosphoric ester phosphorus (concentra- tions, in millimoles, of each being 0.71–1.36, 2.23–3.13 and 0.86–1.45, respectively). Clearly, the plasma compart- ment contains only a small fraction of total body phospho- rus, and changes in concentrations of inorganic phosphate do not necessarily reflect total body stores of phosphorus. Phosphorus homeostasis and its regulation: The amounts of phosphorus moving across various epithelial tissues and organs are depicted in Fig. 1 [3]. Phosphorus is absorbed in the small intestine, predominantly in the jejunum, by both transcellular and paracellular processes (Fig. 1), the former process being mediated by sodium–phosphate type IIb