Review

Pediatric Nephrology

, Volume 21, Issue 8, pp 1067-1074

First online:

Role of prostaglandins in the pathogenesis of X-linked hypophosphatemia

  • Michel BaumAffiliated withDepartment of Pediatrics, University of Texas Southwestern Medical Center at Dallas Email author 
  • , Ashu SyalAffiliated withDepartment of Pediatrics, University of Texas Southwestern Medical Center at Dallas
  • , Raymond QuigleyAffiliated withDepartment of Pediatrics, University of Texas Southwestern Medical Center at Dallas
  • , Mouin SeikalyAffiliated withDepartment of Pediatrics, University of Texas Southwestern Medical Center at Dallas

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Abstract

X-linked hypophosphatemia is an X-linked dominant disorder resulting from a mutation in the PHEX gene. PHEX stands for phosphate-regulating gene with endopeptidase activity, which is located on the X chromosome. Patients with X-linked hypophosphatemia have hypophosphatemia due to renal phosphate wasting and low or inappropriately normal levels of 1,25-dihydroxyvitamin D. The renal phosphate wasting is not intrinsic to the kidney but likely due to an increase in serum levels of fibroblast growth factor-23 (FGF-23), and perhaps other phosphate-wasting peptides previously known as phosphatonins. Patients with X-linked hypophosphatemia have short stature, rickets, bone pain and dental abscesses. Current therapy is oral phosphate and vitamin D which effectively treats the rickets and bone pain but does not adequately improve short stature. In this review, we describe recent observations using Hyp mice; mice with the same mutation as patients with X-linked hypophosphatemia. We have recently found that Hyp mice have abnormal renal prostaglandin production, which may be an important factor in the pathogenesis of this disorder. Administration of FGF-23 in vivo results in phosphaturia and an increase in prostaglandin excretion, and FGF-23 increases proximal tubule prostaglandin production in vitro. In Hyp mice, indomethacin improves the phosphate transport defect in vitro and in vivo. Whether indomethacin has the same effect in patients with X-linked hypophosphatemia is unknown.

Keywords

Hyp mouse FGF-23, PGE2