Lack of FGF23 Response to Acute Changes in Serum Calcium and PTH in Humans

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2014 Jul 26

PMID 25062462

Citations 9

Authors

Katherine Wesseling-Perry

Hejing Wang

Robert Elashoff

Barbara Gales

Harald Juppner

Isidro B Salusky

Affiliations

Soon will be listed here.

Abstract

Context: 1,25-Dihydroxyvitamin D (1,25D) administration and long-term increases in phosphate, PTH, and calcium concentrations are associated with increases in circulating fibroblast growth factor 23 (FGF23); however, whether or not acute changes in serum calcium modulate short-term FGF23 release is unknown.

Objective/design: To assess the direct effect of acute changes in calcium and PTH on circulating FGF23 levels.

Setting: A university clinical and translational research center.

Patients/participants: Twelve healthy volunteers and 10 dialysis patients.

Interventions: Calcium gluconate and sodium citrate were infused for 120 minutes on 2 consecutive days.

Main Outcome Measures: Serum levels of ionized calcium, phosphorus, PTH, 1,25D, and plasma C-terminal FGF23 levels were obtained at 0, 13, 30, 60, 90, and 120 minutes during the infusions.

Results: During the calcium infusion, serum calcium concentrations increased from 1.33 ± 0.01 to 1.57 ± 0.04 mmol/L (P < .05 from baseline) and from 1.20 ± 0.05 to 1.50 ± 0.03 mmol/L (P < .05 from baseline) in healthy subjects and in dialysis patients, respectively, whereas serum calcium values decreased from 1.33 ± 0.01 to 1.03 ± 0.02 mmol/L (P < .05 from baseline) and from 1.26 ± 0.04 to 1.07 ± 0.03 mmol/L (P < .05 from baseline) in the two groups, respectively during the sodium citrate infusion. PTH levels decreased from 35 (29, 57) to 8 (2,10) pg/mL (healthy subjects) (P < .05 from baseline) and from 292 (109, 423) to 44 (28, 86) pg/mL (dialysis patients) (P < .05 from baseline) during the calcium infusion and rose from 31 (25, 56) to 122 (95, 157) pg/mL and from 281 (117, 607) to 468 (169, 928) pg/mL (P < .05 from baseline) during sodium citrate infusion. Serum 1,25D levels and plasma FGF23 values remained unchanged during both infusions in both groups.

Conclusions: Short-term changes in calcium and PTH levels do not affect FGF23 concentrations in either healthy volunteers or dialysis patients.

Citing Articles

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Shedding Light on the Complex Regulation of FGF23.

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FGF23 Is Not Associated With Age-Related Changes in Phosphate, but Enhances Renal Calcium Reabsorption in Girls.

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Dietary factors and fibroblast growth factor-23 levels in young adults with African ancestry.

Kosk D, Kramer H, Luke A, Camacho P, Bovet P, Rhule J J Bone Miner Metab. 2016; 35(6):666-674.

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References

Naveh-Many T, Bell O, Silver J, Kilav R . Cis and trans acting factors in the regulation of parathyroid hormone (PTH) mRNA stability by calcium and phosphate. FEBS Lett. 2002; 529(1):60-4. DOI: 10.1016/s0014-5793(02)03259-3. View

Moallem E, Kilav R, Silver J, Naveh-Many T . RNA-Protein binding and post-transcriptional regulation of parathyroid hormone gene expression by calcium and phosphate. J Biol Chem. 1998; 273(9):5253-9. DOI: 10.1074/jbc.273.9.5253. View

Kifor O, Moore Jr F, Wang P, Goldstein M, Vassilev P, KIFOR I . Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab. 1996; 81(4):1598-606. DOI: 10.1210/jcem.81.4.8636374. View

Ramirez J, Goodman W, Gornbein J, Menezes C, Moulton L, Segre G . Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism. J Clin Endocrinol Metab. 1993; 76(6):1489-94. DOI: 10.1210/jcem.76.6.8501155. View

Rodriguez-Ortiz M, Lopez I, Munoz-Castaneda J, Martinez-Moreno J, Ramirez A, Pineda C . Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol. 2012; 23(7):1190-7. PMC: 3380648. DOI: 10.1681/ASN.2011101006. View

Shimada T, Yamazaki Y, Takahashi M, Hasegawa H, Urakawa I, Oshima T . Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol Renal Physiol. 2005; 289(5):F1088-95. DOI: 10.1152/ajprenal.00474.2004. View

Slatopolsky E, Finch J, CLAY P, Martin D, Sicard G, Singer G . A novel mechanism for skeletal resistance in uremia. Kidney Int. 2000; 58(2):753-61. DOI: 10.1046/j.1523-1755.2000.00222.x. View

Takahashi H, Komaba H, Takahashi Y, Sawada K, Tatsumi R, Kanai G . Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism. J Clin Endocrinol Metab. 2014; 99(4):E652-8. DOI: 10.1210/jc.2013-4050. View

Wetmore J, Santos P, Mahnken J, Krebill R, Menard R, Gutta H . Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD. J Clin Endocrinol Metab. 2010; 96(1):E57-64. PMC: 3038477. DOI: 10.1210/jc.2010-1277. View

10.

Wesseling-Perry K, Harkins G, Wang H, Elashoff R, Gales B, Horwitz M . The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84). J Clin Endocrinol Metab. 2010; 95(6):2772-80. PMC: 2902063. DOI: 10.1210/jc.2009-1909. View

11.

Sanchez C, Goodman W, Ramirez J, Gales B, Belin T, Segre G . Calcium-regulated parathyroid hormone secretion in adynamic renal osteodystrophy. Kidney Int. 1995; 48(3):838-43. DOI: 10.1038/ki.1995.359. View

12.

Burnett-Bowie S, Henao M, Dere M, Lee H, Leder B . Effects of hPTH(1-34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men. J Bone Miner Res. 2009; 24(10):1681-5. PMC: 2743281. DOI: 10.1359/jbmr.090406. View

13.

Antoniucci D, Yamashita T, Portale A . Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab. 2006; 91(8):3144-9. DOI: 10.1210/jc.2006-0021. View

14.

Lavi-Moshayoff V, Wasserman G, Meir T, Silver J, Naveh-Many T . PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010; 299(4):F882-9. DOI: 10.1152/ajprenal.00360.2010. View

15.

Cancela A, Oliveira R, Graciolli F, Dos Reis L, Barreto F, Barreto D . Fibroblast growth factor 23 in hemodialysis patients: effects of phosphate binder, calcitriol and calcium concentration in the dialysate. Nephron Clin Pract. 2010; 117(1):c74-82. DOI: 10.1159/000319650. View

16.

Lim K, Lu T, Molostvov G, Lee C, Lam F, Zehnder D . Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation. 2012; 125(18):2243-55. DOI: 10.1161/CIRCULATIONAHA.111.053405. View

17.

Imanishi Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A . FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int. 2004; 65(5):1943-6. DOI: 10.1111/j.1523-1755.2004.00604.x. View

18.

David V, Dai B, Martin A, Huang J, Han X, Quarles L . Calcium regulates FGF-23 expression in bone. Endocrinology. 2013; 154(12):4469-82. PMC: 3836077. DOI: 10.1210/en.2013-1627. View

19.

Perwad F, Azam N, Zhang M, Yamashita T, Tenenhouse H, Portale A . Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology. 2005; 146(12):5358-64. DOI: 10.1210/en.2005-0777. View

20.

Gutierrez O, Smith K, Barchi-Chung A, Patel N, Isakova T, Wolf M . (1-34) Parathyroid hormone infusion acutely lowers fibroblast growth factor 23 concentrations in adult volunteers. Clin J Am Soc Nephrol. 2012; 7(1):139-45. PMC: 3265347. DOI: 10.2215/CJN.06240611. View