Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women.
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It is proposed that intravenous iron lowers cF GF23 in humans by reducing fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.Abstract:
Fibroblast growth factor 23 (FGF23) is an osteocyte-derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild-type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system. We tested the association of iron deficiency anemia with C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 55 women with a history of heavy uterine bleeding, and assessed the longitudinal biochemical response over 35 days to equivalent doses of randomly-assigned, intravenous elemental iron in the form of ferric carboxymaltose (FCM) or iron dextran. Iron deficiency was associated with markedly elevated cFGF23 (807.8 ± 123.9 relative units [RU]/mL) but normal iFGF23 (28.5 ± 1.1 pg/mL) levels at baseline. Within 24 hours of iron administration, cFGF23 levels fell by approximately 80% in both groups. In contrast, iFGF23 transiently increased in the FCM group alone, and was followed by a transient, asymptomatic reduction in serum phosphate <2.0 mg/dL in 10 women in the FCM group compared to none in the iron dextran group. Reduced serum phosphate was accompanied by increased urinary fractional excretion of phosphate, decreased calcitriol levels, and increased parathyroid hormone levels. These findings suggest that iron deficiency increases cFGF23 levels, and that certain iron preparations temporarily increase iFGF23 levels. We propose that intravenous iron lowers cFGF23 in humans by reducing fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.read more
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References
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Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.
Orlando M. Gutiérrez,Michael Mannstadt,Tamara Isakova,Jose Alejandro Rauh-Hain,Hector Tamez,Anand Shah,Kelsey Smith,Hang Lee,Ravi Thadhani,Harald Jüppner,Myles Wolf,Myles Wolf +11 more
TL;DR: Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment, and a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease is investigated.
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Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia
Takashi Shimada,Satoru Mizutani,Takanori Muto,Takashi Yoneya,Rieko Hino,Shu Takeda,Yasuhiro Takeuchi,Toshiro Fujita,Seiji Fukumoto,Takeyoshi Yamashita +9 more
TL;DR: It is concluded that overproduction of F GF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF 23.
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Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers.
TL;DR: Circulating FGF-23 was significantly elevated in patients with CKD and its concentration correlated with renal creatinine clearance, and in healthy volunteers, F GF-23 levels did not change after phosphate deprivation or phosphate loading.
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