Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status.
BACKGROUND
Circulating fibroblast growth factor (FGF)-23 is variably elevated in individuals with X-linked hypophosphatemia (XLH), and klotho has recently been shown to effect renal phosphate handling, yet limited data are available on circulating FGF23 and klotho in XLH.


OBJECTIVE
The objective of the study was to characterize circulating FGF23 and klotho in XLH.


METHODS
Children and adults with XLH withheld medication for 14 d. Fasting serum FGF23, PTH, klotho, phosphate, and 1,25 dihydroxyvitamin D were obtained. Treated adults were also sampled, and circadian sampling was performed in selected individuals.


METHODS
The study was conducted at a hospital research unit at an academic medical center.


METHODS
Participants included 23 individuals with XLH and eight controls.


METHODS
There were no interventions.


METHODS
Serum klotho and FGF23 were measured.


RESULTS
FGF23 was greater in XLH than in controls and greater in treated XLH subjects compared with XLH subjects not receiving medical therapy. Children had higher klotho levels than adults, but values in XLH were similar to controls. A strong positive correlation between FGF23 and PTH was found in XLH subjects, whereas there was no relationship between these variables in controls. Circulating klotho, but not FGF23, has a diurnal pattern.


CONCLUSIONS
Serum klotho declines with age and demonstrates circadian variation but is normal in XLH. Serum FGF23 is similar in children and adults, is elevated in XLH, further increases with therapy, and demonstrates no diurnal variation. The direct relationship between FGF23 and PTH in subjects with XLH suggests that FGF23 regulation of PTH secretion is aberrant in this disorder.
Carpenter
Thomas O
TO
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA. thomas.carpenter@yale.edu
Insogna
Karl L
KL
Zhang
Jane H
JH
Ellis
Bruce
B
Nieman
Sherril
S
Simpson
Christine
C
Olear
Elizabeth
E
Gundberg
Caren M
CM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002117:Calcitriol / Q000627:therapeutic use; D002648:Child; D002940:Circadian Rhythm / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D053098:Familial Hypophosphatemic Rickets / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D040181:Genetic Diseases, X-Linked; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood / Q000627:therapeutic use; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D050071:Bone Density Conservation Agents; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol