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Published ahead of print on February 6, 2008
Clinical Journal of the American Society of Nephrology
© 2008 American Society of Nephrology
doi: 10.2215/CJN.04981107
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Received November 14, 2007
Accepted on January 7, 2008

ORIGINAL ARTICLES

Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets

Uri S. Alon *1, Rachel Levy-Olomucki *, Wayne V. Moore {dagger}, Jason Stubbs {ddagger}, Shiguang Liu {ddagger}, and L. Darryl Quarles {ddagger}

*Pediatric Nephrology, Bone and Mineral Disorders Clinic and {dagger}Pediatric Endocrinology, Children’s Mercy Hospital, University of Missouri, Kansas City, Missouri; and {ddagger}the Kidney Institute, University of Kansas Medical Center, Kansas University Medical Center, Kansas City, Kansas


1 To whom correspondence should be addressed. E-mail: ualon{at}cmh.edu.


  Abstract

Background and Objectives: The treatment for X-linked hypophosphatemia (XLH) with phosphate and calcitriol can be complicated by secondary hyperparathyroidism and nephrocalcinosis. Furthermore, vitamin D and phosphate stimulate FGF23 production, the pathogenic factor causing XLH. We investigated in XLH patients: 1) whether treatment with the calcimimetic agent, cinacalcet, will block the rise in parathyroid hormone (PTH) caused by phosphate administration; and 2) whether treatment with oral phosphate and calcitriol increases FGF23 levels.

Design, Setting, Participants, and Measurements: Eight subjects with XLH were given a single oral dose of phosphate, followed the next day by combined treatment with phosphate and cinacalcet. Serum measurements of ionized calcium (Ca), phosphate, creatinine, intact PTH, 1,25(OH)2D, FGF23, and tubular threshold for phosphate/glomerular filtration rate (TP/GFR) were assessed in response to short-term treatment with phosphate and cinacalcet and compared with long-term administration of phosphate and calcitriol.

Results: Oral phosphate load increased serum phosphate, decreased ionized calcium, and increased PTH. Twenty-four hours later, FGF23 significantly increased and 1,25(OH)2D decreased. The concomitant administration of phosphate and cinacalcet resulted in further decrease in serum Ca2+ but suppression of PTH and greater increase in serum phosphate and TP/GFR. Chronic treatment with phosphate and calcitriol resulted in a smaller increment in serum phosphate and high serum FGF23.

Conclusions: Traditional therapy of XLH with phosphate and calcitriol elevates FGF23 and has the potential to stimulate PTH. Short-term treatment with cinacalcet suppresses PTH, leading to increase in TP/GFR and serum phosphate. Thus, long-term clinical studies are needed to investigate whether cinacalcet may be a useful adjuvant in the treatment of XLH, allowing the use of lower doses of phosphate and calcitriol.




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