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Erschienen in: Calcified Tissue International 3/2017

09.11.2016 | Review

Novel Faces of Fibroblast Growth Factor 23 (FGF23): Iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury

verfasst von: Mehmet Kanbay, Marc Vervloet, Mario Cozzolino, Dimitrie Siriopol, Adrian Covic, David Goldsmith, Yalcin Solak

Erschienen in: Calcified Tissue International | Ausgabe 3/2017

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Abstract

FGF23 is a hormone that appears as the core regulator of phosphate metabolism. Great deal of data has accumulated to demonstrate increased FGF23 secretion from the bone to compensate for even subtle increases in serum phosphorus long before intact PTH. However, recent evidence points to the fact that actions and interactions of FGF23 are not limited solely to phosphate metabolism. FGF23 may be implicated in iron metabolism and erythropoiesis, inflammation, insulin resistance, proteinuria, acute kidney injury and left ventricular hypertrophy. In this review, we will summarize latest experimental and clinical data examining impact of FGF23 on aforementioned pathophysiologic pathways/disorders.
Literatur
1.
Zurück zum Zitat Okada M, Imamura K, Iida M, Fuchigami T, Omae T (1983) Hypophosphatemia induced by intravenous administration of saccharated iron oxide. Klin Wochenschr 61(2):99–102CrossRefPubMed Okada M, Imamura K, Iida M, Fuchigami T, Omae T (1983) Hypophosphatemia induced by intravenous administration of saccharated iron oxide. Klin Wochenschr 61(2):99–102CrossRefPubMed
2.
Zurück zum Zitat Sato K, Nohtomi K, Demura H, Takeuchi A, Kobayashi T, Kazama J et al (1997) Saccharated ferric oxide (SFO)-induced osteomalacia: in vitro inhibition by SFO of bone formation and 1,25-dihydroxy-vitamin D production in renal tubules. Bone 21(1):57–64CrossRefPubMed Sato K, Nohtomi K, Demura H, Takeuchi A, Kobayashi T, Kazama J et al (1997) Saccharated ferric oxide (SFO)-induced osteomalacia: in vitro inhibition by SFO of bone formation and 1,25-dihydroxy-vitamin D production in renal tubules. Bone 21(1):57–64CrossRefPubMed
3.
Zurück zum Zitat Schouten BJ, Doogue MP, Soule SG, Hunt PJ (2009) Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem 46(Pt 2):167–169CrossRefPubMed Schouten BJ, Doogue MP, Soule SG, Hunt PJ (2009) Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem 46(Pt 2):167–169CrossRefPubMed
4.
Zurück zum Zitat Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG (2009) FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 94(7):2332–2337CrossRefPubMed Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG (2009) FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 94(7):2332–2337CrossRefPubMed
5.
Zurück zum Zitat Hryszko T, Rydzewska-Rosolowska A, Brzosko S, Koc-Zorawska E, Mysliwiec M (2012) Low molecular weight iron dextran increases fibroblast growth factor-23 concentration, together with parathyroid hormone decrease in hemodialyzed patients. Ther Apher Dial 16(2):146–151CrossRefPubMed Hryszko T, Rydzewska-Rosolowska A, Brzosko S, Koc-Zorawska E, Mysliwiec M (2012) Low molecular weight iron dextran increases fibroblast growth factor-23 concentration, together with parathyroid hormone decrease in hemodialyzed patients. Ther Apher Dial 16(2):146–151CrossRefPubMed
6.
Zurück zum Zitat Block GA, Fishbane S, Rodriguez M, Smits G, Shemesh S, Pergola PE et al (2015) A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD stages 3–5. Am J Kidney Dis 65(5):728–736CrossRefPubMed Block GA, Fishbane S, Rodriguez M, Smits G, Shemesh S, Pergola PE et al (2015) A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD stages 3–5. Am J Kidney Dis 65(5):728–736CrossRefPubMed
7.
Zurück zum Zitat Iguchi A, Kazama JJ, Yamamoto S, Yoshita K, Watanabe Y, Iino N et al (2015) Administration of ferric citrate hydrate decreases circulating FGF23 levels independently of serum phosphate levels in hemodialysis patients with iron deficiency. Nephron 131(3):161–166PubMed Iguchi A, Kazama JJ, Yamamoto S, Yoshita K, Watanabe Y, Iino N et al (2015) Administration of ferric citrate hydrate decreases circulating FGF23 levels independently of serum phosphate levels in hemodialysis patients with iron deficiency. Nephron 131(3):161–166PubMed
8.
Zurück zum Zitat Prats M, Font R, Garcia C, Cabre C, Jariod M, Vea AM (2013) Effect of ferric carboxymaltose on serum phosphate and C-terminal FGF23 levels in non-dialysis chronic kidney disease patients: post hoc analysis of a prospective study. BMC Nephrol 14:167CrossRefPubMedPubMedCentral Prats M, Font R, Garcia C, Cabre C, Jariod M, Vea AM (2013) Effect of ferric carboxymaltose on serum phosphate and C-terminal FGF23 levels in non-dialysis chronic kidney disease patients: post hoc analysis of a prospective study. BMC Nephrol 14:167CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Yamashita K, Mizuiri S, Nishizawa Y, Kenichiro S, Doi S, Masaki T (2016) Oral iron supplementation with sodium ferrous citrate reduces the serum intact and C-terminal FGF23 levels of maintenance hemodialysis patients. Nephrology (Carlton). doi:10.1111/nep.12909 Yamashita K, Mizuiri S, Nishizawa Y, Kenichiro S, Doi S, Masaki T (2016) Oral iron supplementation with sodium ferrous citrate reduces the serum intact and C-terminal FGF23 levels of maintenance hemodialysis patients. Nephrology (Carlton). doi:10.​1111/​nep.​12909
10.
Zurück zum Zitat Imel EA, Liu Z, McQueen AK, Acton D, Acton A, Padgett LR et al (2016) Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women. Bone 86:98–105CrossRefPubMed Imel EA, Liu Z, McQueen AK, Acton D, Acton A, Padgett LR et al (2016) Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women. Bone 86:98–105CrossRefPubMed
11.
Zurück zum Zitat Wolf M, Koch TA, Bregman DB (2013) Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res 28(8):1793–1803CrossRefPubMed Wolf M, Koch TA, Bregman DB (2013) Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res 28(8):1793–1803CrossRefPubMed
12.
Zurück zum Zitat Bozentowicz-Wikarek M, Kocelak P, Owczarek A, Olszanecka-Glinianowicz M, Mossakowska M, Skalska A et al (2015) Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population? Clin Biochem 48(6):431–436CrossRefPubMed Bozentowicz-Wikarek M, Kocelak P, Owczarek A, Olszanecka-Glinianowicz M, Mossakowska M, Skalska A et al (2015) Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population? Clin Biochem 48(6):431–436CrossRefPubMed
13.
Zurück zum Zitat van Breda F, Emans ME, van der Putten K, Braam B, van Ittersum FJ, Kraaijenhagen RJ et al (2015) Relation between red cell distribution width and fibroblast growth factor 23 cleaving in patients with chronic kidney disease and heart failure. PLoS ONE 10(6):e0128994CrossRefPubMedPubMedCentral van Breda F, Emans ME, van der Putten K, Braam B, van Ittersum FJ, Kraaijenhagen RJ et al (2015) Relation between red cell distribution width and fibroblast growth factor 23 cleaving in patients with chronic kidney disease and heart failure. PLoS ONE 10(6):e0128994CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Farrow EG, Yu X, Summers LJ, Davis SI, Fleet JC, Allen MR et al (2011) Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci USA 108(46):E1146–E1155CrossRefPubMedPubMedCentral Farrow EG, Yu X, Summers LJ, Davis SI, Fleet JC, Allen MR et al (2011) Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci USA 108(46):E1146–E1155CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Pereira RC, Juppner H, Gales B, Salusky IB, Wesseling-Perry K (2015) Osteocytic protein expression response to doxercalciferol therapy in pediatric dialysis patients. PLoS ONE 10(3):e0120856CrossRefPubMedPubMedCentral Pereira RC, Juppner H, Gales B, Salusky IB, Wesseling-Perry K (2015) Osteocytic protein expression response to doxercalciferol therapy in pediatric dialysis patients. PLoS ONE 10(3):e0120856CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Coe LM, Madathil SV, Casu C, Lanske B, Rivella S, Sitara D (2014) FGF-23 is a negative regulator of prenatal and postnatal erythropoiesis. J Biol Chem 289(14):9795–9810CrossRefPubMedPubMedCentral Coe LM, Madathil SV, Casu C, Lanske B, Rivella S, Sitara D (2014) FGF-23 is a negative regulator of prenatal and postnatal erythropoiesis. J Biol Chem 289(14):9795–9810CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Saito K, Ishizaka N, Mitani H, Ohno M, Nagai R (2003) Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat. FEBS Lett 551(1–3):58–62CrossRefPubMed Saito K, Ishizaka N, Mitani H, Ohno M, Nagai R (2003) Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat. FEBS Lett 551(1–3):58–62CrossRefPubMed
18.
Zurück zum Zitat Braithwaite V, Prentice AM, Doherty C, Prentice A (2012) FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study. Int J Pediatr Endocrinol 2012(1):27CrossRefPubMedPubMedCentral Braithwaite V, Prentice AM, Doherty C, Prentice A (2012) FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study. Int J Pediatr Endocrinol 2012(1):27CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat David V, Martin A, Isakova T, Spaulding C, Qi L, Ramirez V et al (2015) Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 89(1):135–146. doi:10.1038/ki.2015.290 CrossRef David V, Martin A, Isakova T, Spaulding C, Qi L, Ramirez V et al (2015) Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 89(1):135–146. doi:10.​1038/​ki.​2015.​290 CrossRef
20.
Zurück zum Zitat Clinkenbeard EL, Farrow EG, Summers LJ, Cass TA, Roberts JL, Bayt CA et al (2014) Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice. J Bone Miner Res 29(2):361–369CrossRefPubMedPubMedCentral Clinkenbeard EL, Farrow EG, Summers LJ, Cass TA, Roberts JL, Bayt CA et al (2014) Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice. J Bone Miner Res 29(2):361–369CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Sato H, James Kazama J, Murasawa A, Otani H, Abe A, Ito S et al (2016) Serum fibroblast growth factor 23 (FGF23) in patients with rheumatoid arthritis. Intern Med 55(2):121–126CrossRefPubMed Sato H, James Kazama J, Murasawa A, Otani H, Abe A, Ito S et al (2016) Serum fibroblast growth factor 23 (FGF23) in patients with rheumatoid arthritis. Intern Med 55(2):121–126CrossRefPubMed
22.
Zurück zum Zitat Pathak JL, Bakker AD, Luyten FP, Verschueren P, Lems WF, Klein-Nulend J et al (2016) Systemic inflammation affects human osteocyte-specific protein and cytokine expression. Calcif Tissue Int 98:596–608CrossRefPubMed Pathak JL, Bakker AD, Luyten FP, Verschueren P, Lems WF, Klein-Nulend J et al (2016) Systemic inflammation affects human osteocyte-specific protein and cytokine expression. Calcif Tissue Int 98:596–608CrossRefPubMed
23.
Zurück zum Zitat Holecki M, Chudek J, Owczarek A, Olszanecka-Glinianowicz M, Bozentowicz-Wikarek M, Dulawa J et al (2015) Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly. Clin Endocrinol 82(6):900–909CrossRef Holecki M, Chudek J, Owczarek A, Olszanecka-Glinianowicz M, Bozentowicz-Wikarek M, Dulawa J et al (2015) Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly. Clin Endocrinol 82(6):900–909CrossRef
24.
Zurück zum Zitat Hanks LJ, Casazza K, Judd SE, Jenny NS, Gutierrez OM (2015) Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults. PLoS ONE 10(3):e0122885CrossRefPubMedPubMedCentral Hanks LJ, Casazza K, Judd SE, Jenny NS, Gutierrez OM (2015) Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults. PLoS ONE 10(3):e0122885CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Feldman HI, Appel LJ, Chertow GM, Cifelli D, Cizman B, Daugirdas J et al (2003) The chronic renal insufficiency cohort (CRIC) study: design and methods. J Am Soc Nephrol 14(7 Suppl 2):S148–S153CrossRefPubMed Feldman HI, Appel LJ, Chertow GM, Cifelli D, Cizman B, Daugirdas J et al (2003) The chronic renal insufficiency cohort (CRIC) study: design and methods. J Am Soc Nephrol 14(7 Suppl 2):S148–S153CrossRefPubMed
26.
Zurück zum Zitat Munoz Mendoza J, Isakova T, Ricardo AC, Xie H, Navaneethan SD, Anderson AH et al (2012) Fibroblast growth factor 23 and Inflammation in CKD. Clin J Am Soc Nephrol 7(7):1155–1162CrossRefPubMedPubMedCentral Munoz Mendoza J, Isakova T, Ricardo AC, Xie H, Navaneethan SD, Anderson AH et al (2012) Fibroblast growth factor 23 and Inflammation in CKD. Clin J Am Soc Nephrol 7(7):1155–1162CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Han X, Li L, Yang J, King G, Xiao Z, Quarles LD (2016) Counter-regulatory paracrine actions of FGF-23 and 1,25(OH)2 D in macrophages. FEBS Lett 590(1):53–67CrossRefPubMedPubMedCentral Han X, Li L, Yang J, King G, Xiao Z, Quarles LD (2016) Counter-regulatory paracrine actions of FGF-23 and 1,25(OH)2 D in macrophages. FEBS Lett 590(1):53–67CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Rossaint J, Oehmichen J, Van Aken H, Reuter S, Pavenstadt HJ, Meersch M et al (2016) FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J Clin Invest 126(3):962–974CrossRefPubMedPubMedCentral Rossaint J, Oehmichen J, Van Aken H, Reuter S, Pavenstadt HJ, Meersch M et al (2016) FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J Clin Invest 126(3):962–974CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat de Seigneux S, Courbebaisse M, Rutkowski JM, Wilhelm-Bals A, Metzger M, Khodo SN et al (2015) Proteinuria increases plasma phosphate by altering its tubular handling. J Am Soc Nephrol 26(7):1608–1618CrossRefPubMed de Seigneux S, Courbebaisse M, Rutkowski JM, Wilhelm-Bals A, Metzger M, Khodo SN et al (2015) Proteinuria increases plasma phosphate by altering its tubular handling. J Am Soc Nephrol 26(7):1608–1618CrossRefPubMed
30.
Zurück zum Zitat Zanchi C, Locatelli M, Benigni A, Corna D, Tomasoni S, Rottoli D et al (2013) Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor. PLoS ONE 8(8):e70775CrossRefPubMedPubMedCentral Zanchi C, Locatelli M, Benigni A, Corna D, Tomasoni S, Rottoli D et al (2013) Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor. PLoS ONE 8(8):e70775CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Aizawa T, Ishizaka N, Taguchi J, Nagai R, Mori I, Tang SS et al (2000) Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats: possible role in renoprotection. Hypertension 35(3):800–806CrossRefPubMed Aizawa T, Ishizaka N, Taguchi J, Nagai R, Mori I, Tang SS et al (2000) Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats: possible role in renoprotection. Hypertension 35(3):800–806CrossRefPubMed
32.
Zurück zum Zitat Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T et al (2002) In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 39(4):838–843CrossRefPubMed Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T et al (2002) In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 39(4):838–843CrossRefPubMed
33.
Zurück zum Zitat Titan SM, Zatz R, Graciolli FG, dos Reis LM, Barros RT, Jorgetti V et al (2011) FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 6(2):241–247CrossRefPubMedPubMedCentral Titan SM, Zatz R, Graciolli FG, dos Reis LM, Barros RT, Jorgetti V et al (2011) FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 6(2):241–247CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Yilmaz MI, Sonmez A, Saglam M, Yaman H, Kilic S, Demirkaya E et al (2010) FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int 78(7):679–685CrossRefPubMed Yilmaz MI, Sonmez A, Saglam M, Yaman H, Kilic S, Demirkaya E et al (2010) FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int 78(7):679–685CrossRefPubMed
35.
Zurück zum Zitat Vervloet MG, van Zuilen AD, Heijboer AC, ter Wee PM, Bots ML, Blankestijn PJ et al (2012) Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease: an analysis of the MASTERPLAN cohort. BMC Nephrol 13:20CrossRefPubMedPubMedCentral Vervloet MG, van Zuilen AD, Heijboer AC, ter Wee PM, Bots ML, Blankestijn PJ et al (2012) Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease: an analysis of the MASTERPLAN cohort. BMC Nephrol 13:20CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Yilmaz MI, Sonmez A, Saglam M, Kurt YG, Unal HU, Karaman M et al (2014) Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy. Am J Nephrol 40(3):208–214CrossRefPubMed Yilmaz MI, Sonmez A, Saglam M, Kurt YG, Unal HU, Karaman M et al (2014) Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy. Am J Nephrol 40(3):208–214CrossRefPubMed
37.
Zurück zum Zitat Zoccali C, Ruggenenti P, Perna A, Leonardis D, Tripepi R, Tripepi G et al (2011) Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition. J Am Soc Nephrol 22(10):1923–1930CrossRefPubMedPubMedCentral Zoccali C, Ruggenenti P, Perna A, Leonardis D, Tripepi R, Tripepi G et al (2011) Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition. J Am Soc Nephrol 22(10):1923–1930CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Humalda JK, Lambers Heerspink HJ, Kwakernaak AJ, Slagman MC, Waanders F, Vervloet MG et al (2015) Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade. Am J Kidney Dis 65(2):259–266CrossRefPubMed Humalda JK, Lambers Heerspink HJ, Kwakernaak AJ, Slagman MC, Waanders F, Vervloet MG et al (2015) Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade. Am J Kidney Dis 65(2):259–266CrossRefPubMed
39.
Zurück zum Zitat Sonneveld R, Hoenderop JG, Stavenuiter AW, Ferrantelli E, Baltissen MP, Dijkman HB et al (2016) 1,25-vitamin D3 deficiency induces albuminuria. Am J Pathol 186(4):794–804CrossRefPubMed Sonneveld R, Hoenderop JG, Stavenuiter AW, Ferrantelli E, Baltissen MP, Dijkman HB et al (2016) 1,25-vitamin D3 deficiency induces albuminuria. Am J Pathol 186(4):794–804CrossRefPubMed
40.
Zurück zum Zitat Perez-Gomez MV, Ortiz-Arduan A, Lorenzo-Sellares V (2013) Vitamin D and proteinuria: a critical review of molecular bases and clinical experience. Nefrologia 33(5):716–726PubMed Perez-Gomez MV, Ortiz-Arduan A, Lorenzo-Sellares V (2013) Vitamin D and proteinuria: a critical review of molecular bases and clinical experience. Nefrologia 33(5):716–726PubMed
41.
Zurück zum Zitat de Borst MH, Hajhosseiny R, Tamez H, Wenger J, Thadhani R, Goldsmith DJ (2013) Active vitamin D treatment for reduction of residual proteinuria: a systematic review. J Am Soc Nephrol 24(11):1863–1871CrossRefPubMedPubMedCentral de Borst MH, Hajhosseiny R, Tamez H, Wenger J, Thadhani R, Goldsmith DJ (2013) Active vitamin D treatment for reduction of residual proteinuria: a systematic review. J Am Soc Nephrol 24(11):1863–1871CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Zhang M, Hsu R, Hsu CY, Kordesch K, Nicasio E, Cortez A et al (2011) FGF-23 and PTH levels in patients with acute kidney injury: a cross-sectional case series study. Ann Intensive Care 1(1):21CrossRefPubMedPubMedCentral Zhang M, Hsu R, Hsu CY, Kordesch K, Nicasio E, Cortez A et al (2011) FGF-23 and PTH levels in patients with acute kidney injury: a cross-sectional case series study. Ann Intensive Care 1(1):21CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Leaf DE, Wolf M, Waikar SS, Chase H, Christov M, Cremers S et al (2012) FGF-23 levels in patients with AKI and risk of adverse outcomes. Clin J Am Soc Nephrol 7(8):1217–1223CrossRefPubMedPubMedCentral Leaf DE, Wolf M, Waikar SS, Chase H, Christov M, Cremers S et al (2012) FGF-23 levels in patients with AKI and risk of adverse outcomes. Clin J Am Soc Nephrol 7(8):1217–1223CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Christov M, Waikar SS, Pereira RC, Havasi A, Leaf DE, Goltzman D et al (2013) Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int 84(4):776–785CrossRefPubMedPubMedCentral Christov M, Waikar SS, Pereira RC, Havasi A, Leaf DE, Goltzman D et al (2013) Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int 84(4):776–785CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Ali FN, Hassinger A, Price H, Langman CB (2013) Preoperative plasma FGF23 levels predict acute kidney injury in children: results of a pilot study. Pediatr Nephrol 28(6):959–962CrossRefPubMed Ali FN, Hassinger A, Price H, Langman CB (2013) Preoperative plasma FGF23 levels predict acute kidney injury in children: results of a pilot study. Pediatr Nephrol 28(6):959–962CrossRefPubMed
46.
Zurück zum Zitat Leaf DE, Christov M, Juppner H, Siew E, Ikizler TA, Bian A et al (2016) Fibroblast growth factor 23 levels are elevated and associated with severe acute kidney injury and death following cardiac surgery. Kidney Int 89(4):939–948CrossRefPubMed Leaf DE, Christov M, Juppner H, Siew E, Ikizler TA, Bian A et al (2016) Fibroblast growth factor 23 levels are elevated and associated with severe acute kidney injury and death following cardiac surgery. Kidney Int 89(4):939–948CrossRefPubMed
47.
Zurück zum Zitat Rodriguez-Ortiz ME, Lopez I, Munoz-Castaneda JR, Martinez-Moreno JM, Ramirez AP, Pineda C et al (2012) Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol 23(7):1190–1197CrossRefPubMedPubMedCentral Rodriguez-Ortiz ME, Lopez I, Munoz-Castaneda JR, Martinez-Moreno JM, Ramirez AP, Pineda C et al (2012) Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol 23(7):1190–1197CrossRefPubMedPubMedCentral
48.
Zurück zum Zitat Murer H, Hernando N, Forster I, Biber J (2000) Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 80(4):1373–1409PubMed Murer H, Hernando N, Forster I, Biber J (2000) Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 80(4):1373–1409PubMed
49.
Zurück zum Zitat Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA (2003) Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens 16(11 Pt 1):973–978CrossRefPubMed Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA (2003) Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens 16(11 Pt 1):973–978CrossRefPubMed
50.
Zurück zum Zitat Garland JS, Holden RM, Ross R, Adams MA, Nolan RL, Hopman WM et al (2014) Insulin resistance is associated with fibroblast growth factor-23 in stage 3–5 chronic kidney disease patients. J Diabetes Complications 28(1):61–65CrossRefPubMed Garland JS, Holden RM, Ross R, Adams MA, Nolan RL, Hopman WM et al (2014) Insulin resistance is associated with fibroblast growth factor-23 in stage 3–5 chronic kidney disease patients. J Diabetes Complications 28(1):61–65CrossRefPubMed
51.
Zurück zum Zitat Wojcik M, Dolezal-Oltarzewska K, Janus D, Drozdz D, Sztefko K, Starzyk JB (2012) FGF23 contributes to insulin sensitivity in obese adolescents—preliminary results. Clin Endocrinol 77(4):537–540CrossRef Wojcik M, Dolezal-Oltarzewska K, Janus D, Drozdz D, Sztefko K, Starzyk JB (2012) FGF23 contributes to insulin sensitivity in obese adolescents—preliminary results. Clin Endocrinol 77(4):537–540CrossRef
52.
Zurück zum Zitat Adema AY, van Ittersum FJ, Hoenderop JG, de Borst MH, Nanayakkara PW, Ter Wee PM et al (2016) Reduction of oxidative stress in chronic kidney disease does not increase circulating α-klotho concentrations. PLoS ONE 11(1):e0144121CrossRefPubMedPubMedCentral Adema AY, van Ittersum FJ, Hoenderop JG, de Borst MH, Nanayakkara PW, Ter Wee PM et al (2016) Reduction of oxidative stress in chronic kidney disease does not increase circulating α-klotho concentrations. PLoS ONE 11(1):e0144121CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Hesse M, Frohlich LF, Zeitz U, Lanske B, Erben RG (2007) Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in FGF-23 deficient mice. Matrix Biol 26(2):75–84CrossRefPubMed Hesse M, Frohlich LF, Zeitz U, Lanske B, Erben RG (2007) Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in FGF-23 deficient mice. Matrix Biol 26(2):75–84CrossRefPubMed
54.
Zurück zum Zitat Di Lullo L, Gorini A, Russo D, Santoboni A, Ronco C (2015) Left ventricular hypertrophy in chronic kidney disease patients: from pathophysiology to treatment. Cardiorenal Med 5(4):254–266CrossRefPubMedPubMedCentral Di Lullo L, Gorini A, Russo D, Santoboni A, Ronco C (2015) Left ventricular hypertrophy in chronic kidney disease patients: from pathophysiology to treatment. Cardiorenal Med 5(4):254–266CrossRefPubMedPubMedCentral
55.
Zurück zum Zitat Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T et al (2011) FGF23 induces left ventricular hypertrophy. J Clin Invest 121(11):4393–4408CrossRefPubMedPubMedCentral Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T et al (2011) FGF23 induces left ventricular hypertrophy. J Clin Invest 121(11):4393–4408CrossRefPubMedPubMedCentral
56.
Zurück zum Zitat Touchberry CD, Green TM, Tchikrizov V, Mannix JE, Mao TF, Carney BW et al (2013) FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy. Am J Physiol Endocrinol Metab 304(8):E863–E873CrossRefPubMedPubMedCentral Touchberry CD, Green TM, Tchikrizov V, Mannix JE, Mao TF, Carney BW et al (2013) FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy. Am J Physiol Endocrinol Metab 304(8):E863–E873CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat Kagiyama S, Eguchi S, Frank GD, Inagami T, Zhang YC, Phillips MI (2002) Angiotensin II-induced cardiac hypertrophy and hypertension are attenuated by epidermal growth factor receptor antisense. Circulation 106(8):909–912CrossRefPubMed Kagiyama S, Eguchi S, Frank GD, Inagami T, Zhang YC, Phillips MI (2002) Angiotensin II-induced cardiac hypertrophy and hypertension are attenuated by epidermal growth factor receptor antisense. Circulation 106(8):909–912CrossRefPubMed
58.
Zurück zum Zitat Grabner A, Amaral AP, Schramm K, Singh S, Sloan A, Yanucil C et al (2015) Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy. Cell Metab 22(6):1020–1032CrossRefPubMedPubMedCentral Grabner A, Amaral AP, Schramm K, Singh S, Sloan A, Yanucil C et al (2015) Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy. Cell Metab 22(6):1020–1032CrossRefPubMedPubMedCentral
59.
Zurück zum Zitat Leifheit-Nestler M, Grosse Siemer R, Flasbart K, Richter B, Kirchhoff F, Ziegler WH et al (2016) Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. Nephrol Dial Transplant 31(7):1088–1099CrossRefPubMed Leifheit-Nestler M, Grosse Siemer R, Flasbart K, Richter B, Kirchhoff F, Ziegler WH et al (2016) Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. Nephrol Dial Transplant 31(7):1088–1099CrossRefPubMed
60.
Zurück zum Zitat Di Marco GS, Reuter S, Kentrup D, Grabner A, Amaral AP, Fobker M et al (2014) Treatment of established left ventricular hypertrophy with fibroblast growth factor receptor blockade in an animal model of CKD. Nephrol Dial Transplant 29(11):2028–2035CrossRefPubMedPubMedCentral Di Marco GS, Reuter S, Kentrup D, Grabner A, Amaral AP, Fobker M et al (2014) Treatment of established left ventricular hypertrophy with fibroblast growth factor receptor blockade in an animal model of CKD. Nephrol Dial Transplant 29(11):2028–2035CrossRefPubMedPubMedCentral
61.
Zurück zum Zitat Imel EA, Peacock M, Pitukcheewanont P, Heller HJ, Ward LM, Shulman D et al (2006) Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia. J Clin Endocrinol Metab 91(6):2055–2061CrossRefPubMed Imel EA, Peacock M, Pitukcheewanont P, Heller HJ, Ward LM, Shulman D et al (2006) Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia. J Clin Endocrinol Metab 91(6):2055–2061CrossRefPubMed
62.
Zurück zum Zitat Jovanovich A, Ix JH, Gottdiener J, McFann K, Katz R, Kestenbaum B et al (2013) Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults. Atherosclerosis 231(1):114–119CrossRefPubMed Jovanovich A, Ix JH, Gottdiener J, McFann K, Katz R, Kestenbaum B et al (2013) Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults. Atherosclerosis 231(1):114–119CrossRefPubMed
63.
Zurück zum Zitat Mirza MA, Larsson A, Melhus H, Lind L, Larsson TE (2009) Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 207(2):546–551CrossRefPubMed Mirza MA, Larsson A, Melhus H, Lind L, Larsson TE (2009) Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 207(2):546–551CrossRefPubMed
64.
Zurück zum Zitat Hsu HJ, Wu MS (2009) Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci 337(2):116–122CrossRefPubMed Hsu HJ, Wu MS (2009) Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci 337(2):116–122CrossRefPubMed
65.
Zurück zum Zitat Smith K, deFilippi C, Isakova T, Gutierrez OM, Laliberte K, Seliger S et al (2013) Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD. Am J Kidney Dis 61(1):67–73CrossRefPubMed Smith K, deFilippi C, Isakova T, Gutierrez OM, Laliberte K, Seliger S et al (2013) Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD. Am J Kidney Dis 61(1):67–73CrossRefPubMed
66.
Zurück zum Zitat Xie J, Yoon J, An SW, Kuro-o M, Huang CL (2015) Soluble klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J Am Soc Nephrol JASN 26(5):1150–1160CrossRefPubMed Xie J, Yoon J, An SW, Kuro-o M, Huang CL (2015) Soluble klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J Am Soc Nephrol JASN 26(5):1150–1160CrossRefPubMed
Metadaten
Titel
Novel Faces of Fibroblast Growth Factor 23 (FGF23): Iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury
verfasst von
Mehmet Kanbay
Marc Vervloet
Mario Cozzolino
Dimitrie Siriopol
Adrian Covic
David Goldsmith
Yalcin Solak
Publikationsdatum
09.11.2016
Verlag
Springer US
Erschienen in
Calcified Tissue International / Ausgabe 3/2017
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-016-0206-7

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