title: Intravenous phosphate loading increases fibroblast growth factor 23 in uremic rats.
abstract: Oral phosphate loading and calcitriol stimulate Fibroblast growth factor 23 (FGF23) secretion, but the mechanisms underlying the stimulation of FGF23 remain to be studied. We compared the effect of intravenous phosphate loading with that of oral loading on FGF23 levels in normal and 5/6 nephrectomized uremic rats. Uremic rats (Nx) and sham-operated rats were fed a normal phosphate diet for 2 weeks and then divided into 3 groups: 1) with the same phosphate diet (NP), 2) with a high phosphate diet (HP), and 3) NP rats with intravenous phosphate infusion using a microinfusion pump (IV). Blood and urine were obtained 1 day (early phase) and 7 days (late phase) after the interventions. In the early and late phases, serum phosphate levels and fractional excretion of phosphate (FEP) were comparable in the HP and IV groups in both Sham and Nx rats. Serum phosphate levels in the HP and IV groups were equally and significantly higher than those in the NP group only in the late phase in Nx rats. In the early phase, FGF23 levels were comparable in the NP, HP, and IV groups, but were significantly higher in the HP and IV groups compared to the NP group in the late phase in Nx rats. 1α-hydroxylase and sodium dependent phosphate co-transporter 2a expression levels in the kidney in Nx rats were equally and significantly decreased in the HP and IV groups compared with the NP group, while 24-hydroxylase expression was equally and significantly increased. These results show that chronic intravenous phosphate loading increases bioactive FGF23, indicating that an alternative pathway for FGF23 regulation, in addition to the dietary route, may be present. This pathway is clearer under conditions produced by a kidney injury in which phosphate is easily overloaded.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Arai-Nunota
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Mizobuchi
authors.affiliation: Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Yamazaki-Nakazawa
authors.affiliation: Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kumata
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kondo
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Hosaka
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Koiwa
authors.affiliation: Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kinugasa
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D000818:Animals; D005346:Fibroblast Growth Factors / Q000097:blood*; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D008297:Male; D009392:Nephrectomy; D010710:Phosphates / Q000008:administration & dosage* / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism; D014511:Uremia / Q000097:blood*; D065668:Vitamin D3 24-Hydroxylase / Q000378:metabolism
chemical_list: C505605:Fgf23 protein, rat; D010710:Phosphates; C493556:Slc34a1 protein, rat; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D005346:Fibroblast Growth Factors; D065668:Vitamin D3 24-Hydroxylase