FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study.
BACKGROUND
Parenteral iron administration has been associated with hypophosphatemia. Fibroblast growth factor 23 (FGF23) has a physiological role in phosphate homeostasis via suppression of 25-hydroxyvitamin D [25(OH)D] activation and promotion of phosphaturia. We recently reported a case of iron-induced hypophosphatemic osteomalacia associated with marked FGF23 elevation.


OBJECTIVE
Our objective was to prospectively investigate the effect of parenteral iron polymaltose on phosphate homeostasis and to determine whether any observed change was related to alterations in circulating FGF23.


METHODS
Eight medical outpatients prescribed iv iron polymaltose were recruited. Plasma phosphate, 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], PTH, FGF23, and urinary tubular reabsorption of phosphate were measured prior to iron administration and then weekly for a minimum of 3 wk.


RESULTS
Plasma phosphate fell from 3.4 +/- 0.6 mg/dl at baseline to 1.8 +/- 0.6 mg/dl at wk 1 (P < 0.0001) associated with a fall in percentage tubular reabsorption of phosphate (90 +/- 4.8 to 68 +/- 13; P < 0.001) and 1,25(OH)(2)D (54 +/- 25 to 9 +/- 8 pg/ml; P < 0.001). These indices remained significantly suppressed at wk 2 and 3. 25(OH)D levels were unchanged. FGF23 increased significantly from 43.5 pg/ml at baseline to 177 pg/ml at wk 1 (P < 0.001) with levels correlating with both serum phosphate (R = -0.74; P <0.05) and 1,25(OH)(2)D (R = -0.71; P < 0.05).


CONCLUSIONS
Parenteral iron suppresses renal tubular phosphate reabsorption and 1alpha-hydroxylation of vitamin D resulting in hypophosphatemia. Our data suggest that this is mediated by an increase in FGF23.
Schouten
Belinda J
BJ
Department of Endocrinology, Christchurch Hospital, Christchurch, New Zealand. Belinda.Robb@cdhb.govt.nz
Hunt
Penelope J
PJ
Livesey
John H
JH
Frampton
Chris M
CM
Soule
Steven G
SG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D017674:Hypophosphatemia / Q000097:blood / Q000139:chemically induced*; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D055815:Young Adult
C000717427:FGF23 protein, human; D005290:Ferric Compounds; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D007501:Iron; C013276:teferrol