New Aspects of the Kidney in the Regulation of Fibroblast Growth Factor 23 (FGF23) and Mineral Homeostasis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Nov 25

PMID 33233840

Citations 27

Authors

Maria L Mace

Klaus Olgaard

Ewa Lewin

Affiliations

Soon will be listed here.

Abstract

The bone-derived hormone fibroblast growth factor 23 (FGF23) acts in concert with parathyroid hormone (PTH) and the active vitamin D metabolite calcitriol in the regulation of calcium (Ca) and phosphate (P) homeostasis. More factors are being identified to regulate FGF23 levels and the endocrine loops between the three hormones. The present review summarizes the complex regulation of FGF23 and the disturbed FGF23/Klotho system in chronic kidney disease (CKD). In addition to the reduced ability of the injured kidney to regulate plasma levels of FGF23, several CKD-related factors have been shown to stimulate FGF23 production. The high circulating FGF23 levels have detrimental effects on erythropoiesis, the cardio-vascular system and the immune system, all contributing to the disturbed system biology in CKD. Moreover, new factors secreted by the injured kidney and the uremic calcified vasculature play a role in the mineral and bone disorder in CKD and create a vicious pathological crosstalk.

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References

De Mare A, DHaese P, Verhulst A . The Role of Sclerostin in Bone and Ectopic Calcification. Int J Mol Sci. 2020; 21(9). PMC: 7246472. DOI: 10.3390/ijms21093199. View

Wesseling-Perry K, Pereira R, Tsai E, Ettenger R, Juppner H, Salusky I . FGF23 and mineral metabolism in the early post-renal transplantation period. Pediatr Nephrol. 2013; 28(11):2207-15. PMC: 3796035. DOI: 10.1007/s00467-013-2547-z. View

Christov M, Waikar S, Pereira R, Havasi A, Leaf D, Goltzman D . Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int. 2013; 84(4):776-85. PMC: 3766419. DOI: 10.1038/ki.2013.150. View

Perwad F, Zhang M, Tenenhouse H, Portale A . Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Renal Physiol. 2007; 293(5):F1577-83. DOI: 10.1152/ajprenal.00463.2006. View

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

Musgrove J, Wolf M . Regulation and Effects of FGF23 in Chronic Kidney Disease. Annu Rev Physiol. 2019; 82:365-390. DOI: 10.1146/annurev-physiol-021119-034650. View

Wang W, Lewin E, Olgaard K . Role of calcitonin in the rapid minute-to-minute regulation of plasma Ca2+ homeostasis in the rat. Eur J Clin Invest. 2002; 32(9):674-81. DOI: 10.1046/j.1365-2362.2002.01054.x. View

Zuber A, Centeno G, Pradervand S, Nikolaeva S, Maquelin L, Cardinaux L . Molecular clock is involved in predictive circadian adjustment of renal function. Proc Natl Acad Sci U S A. 2009; 106(38):16523-8. PMC: 2752602. DOI: 10.1073/pnas.0904890106. View

Galitzer H, Ben-Dov I, Silver J, Naveh-Many T . Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. Kidney Int. 2009; 77(3):211-8. DOI: 10.1038/ki.2009.464. View

10.

Sato T, Tominaga Y, Ueki T, Goto N, Matsuoka S, Katayama A . Total parathyroidectomy reduces elevated circulating fibroblast growth factor 23 in advanced secondary hyperparathyroidism. Am J Kidney Dis. 2004; 44(3):481-7. View

11.

Shimada T, Urakawa I, Isakova T, Yamazaki Y, Epstein M, Wesseling-Perry K . Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active. J Clin Endocrinol Metab. 2009; 95(2):578-85. PMC: 2840849. DOI: 10.1210/jc.2009-1603. View

12.

Kumata C, Mizobuchi M, Ogata H, Koiwa F, Nakazawa A, Kondo F . Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism. Am J Nephrol. 2010; 31(3):230-8. DOI: 10.1159/000274483. View

13.

Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register T . CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol. 2014; 25(8):1760-73. PMC: 4116062. DOI: 10.1681/ASN.2013080818. View

14.

Wohrle S, Bonny O, Beluch N, Gaulis S, Stamm C, Scheibler M . FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone. J Bone Miner Res. 2011; 26(10):2486-97. DOI: 10.1002/jbmr.478. View

15.

Wolf M . Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol. 2010; 21(9):1427-35. DOI: 10.1681/ASN.2009121293. View

16.

Sze L, Bernays R, Zwimpfer C, Wiesli P, Brandle M, Schmid C . Excessively high soluble Klotho in patients with acromegaly. J Intern Med. 2012; 272(1):93-7. DOI: 10.1111/j.1365-2796.2012.02542.x. View

17.

Mace M, Gravesen E, Hofman-Bang J, Olgaard K, Lewin E . Key role of the kidney in the regulation of fibroblast growth factor 23. Kidney Int. 2015; 88(6):1304-1313. DOI: 10.1038/ki.2015.231. View

18.

Finch J, Lee D, Liapis H, Ritter C, Zhang S, Suarez E . Phosphate restriction significantly reduces mortality in uremic rats with established vascular calcification. Kidney Int. 2013; 84(6):1145-53. PMC: 6589836. DOI: 10.1038/ki.2013.213. View

19.

Nordholm A, Egstrand S, Gravesen E, Mace M, Morevati M, Olgaard K . Circadian rhythm of activin A and related parameters of mineral metabolism in normal and uremic rats. Pflugers Arch. 2019; 471(8):1079-1094. PMC: 6614158. DOI: 10.1007/s00424-019-02291-2. View

20.

Olauson H, Lindberg K, Amin R, Sato T, Jia T, Goetz R . Parathyroid-specific deletion of Klotho unravels a novel calcineurin-dependent FGF23 signaling pathway that regulates PTH secretion. PLoS Genet. 2013; 9(12):e1003975. PMC: 3861040. DOI: 10.1371/journal.pgen.1003975. View