FGF23 and Phosphate–Cardiovascular Toxins in CKD
Abstract
:1. Introduction
2. FGF23 and its Functions in Phosphate Homeostasis
3. The Role of FGF23 and Phosphate Balance in CKD Progression
3.1. Early Stages of CKD
3.2. End-Stage Kidney Disease
4. The Role of FGF23 and Phosphate in CKD-Associated Cardiovascular Diseases
4.1. Hypertension
4.2. Vascular Calcification
4.3. Inflammation-Mediated Vascular Calcification
4.4. Left Ventricular Hypertrophy
5. Therapeutic Approaches to Inhibit FGF23- and Phosphate-Mediated Cardiovascular Disease
5.1. Restriction of Dietary Phosphate Uptake
5.2. Phosphate Binder
5.3. Nicotinamide
5.4. Magnesium
5.5. Other Approaches
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Thompson, S.; James, M.; Wiebe, N.; Hemmelgarn, B.; Manns, B.; Klarenbach, S.; Tonelli, M. Cause of Death in Patients with Reduced Kidney Function. JASN 2015, 26, 2504–2511. [Google Scholar] [CrossRef] [PubMed]
- Jimbo, R.; Shimosawa, T. Cardiovascular Risk Factors and Chronic Kidney Disease—FGF23: A Key Molecule in the Cardiovascular Disease. Int. J. Hypertens. 2014, 2014, 381082. [Google Scholar] [CrossRef] [PubMed]
- Isakova, T.; Wahl, P.; Vargas, G.S.; Gutiérrez, O.M.; Scialla, J.; Xie, H.; Appleby, D.; Nessel, L.; Bellovich, K.; Chen, J.; et al. Fibroblast Growth Factor 23 is Elevated before Parathyroid Hormone and Phosphate in Chronic Kidney Disease. Kidney Int. 2011, 79, 1370–1378. [Google Scholar] [CrossRef] [PubMed]
- Palmer, S.C.; Hayen, A.; Macaskill, P.; Pellegrini, F.; Craig, J.C.; Elder, G.J.; Strippoli, G.F.M. Serum Levels of Phosphorus, Parathyroid Hormone, and Calcium and Risks of Death and Cardiovascular Disease in Individuals with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. JAMA 2011, 305, 1119–1127. [Google Scholar] [CrossRef] [PubMed]
- Ritter, C.S.; Slatopolsky, E. Phosphate Toxicity in CKD: The Killer among Us. CJASN 2016, 11, 1088–1100. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodelo-Haad, C.; Santamaria, R.; Muñoz-Castañeda, J.R.; Pendón-Ruiz de Mier, M.V.; Martin-Malo, A.; Rodriguez, M. FGF23, Biomarker Or Target? Toxins 2019, 11, 175. [Google Scholar] [CrossRef]
- Shalhoub, V.; Shatzen, E.M.; Ward, S.C.; Davis, J.; Stevens, J.; Bi, V.; Renshaw, L.; Hawkins, N.; Wang, W.; Chen, C.; et al. FGF23 Neutralization Improves Chronic Kidney Disease–associated Hyperparathyroidism Yet Increases Mortality. J. Clin. Investig. 2012, 122, 2543–2553. [Google Scholar] [CrossRef]
- Clinkenbeard, E.L.; Noonan, M.L.; Thomas, J.C.; Ni, P.; Hum, J.M.; Aref, M.; Swallow, E.A.; Moe, S.M.; Allen, M.R.; White, K.E. Increased FGF23 Protects Against Detrimental Cardio-Renal Consequences during Elevated Blood Phosphate in CKD. Jci Insight 2019, 4, 123817. [Google Scholar] [CrossRef]
- Ben-Dov, I.Z.; Galitzer, H.; Lavi-Moshayoff, V.; Goetz, R.; Kuro-o, M.; Mohammadi, M.; Sirkis, R.; Naveh-Many, T.; Silver, J. The Parathyroid is a Target Organ for FGF23 in Rats. J. Clin. Investig. 2007, 117, 4003–4008. [Google Scholar] [CrossRef]
- Saji, F.; Shigematsu, T.; Sakaguchi, T.; Ohya, M.; Orita, H.; Maeda, Y.; Ooura, M.; Mima, T.; Negi, S. Fibroblast Growth Factor 23 Production in Bone is Directly Regulated by 1α, 25-Dihydroxyvitamin D., but Not PTH. Am. J. Physiol.-Ren. Physiol. 2010, 299, F1212–F1217. [Google Scholar] [CrossRef]
- Perwad, F.; Azam, N.; Zhang, M.Y.; Yamashita, T.; Tenenhouse, H.S.; Portale, A.A. Dietary and Serum Phosphorus Regulate Fibroblast Growth Factor 23 Expression and 1,25-Dihydroxyvitamin D Metabolism in Mice. Endocrinology 2005, 146, 5358–5364. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nguyen-Yamamoto, L.; Karaplis, A.C.; St–Arnaud, R.; Goltzman, D. Fibroblast Growth Factor 23 Regulation by Systemic and Local Osteoblast-Synthesized 1,25-Dihydroxyvitamin D. J. Am. Soc. Nephrol. 2017, 28, 586–597. [Google Scholar] [CrossRef] [PubMed]
- Chande, S.; Bergwitz, C. Role of Phosphate Sensing in Bone and Mineral Metabolism. Nat. Rev. Endocrinol. 2018, 1, 637–655. [Google Scholar] [CrossRef] [PubMed]
- Tagliabracci, V.S.; Engel, J.L.; Wiley, S.E.; Xiao, J.; Gonzalez, D.J.; Appaiah, H.N.; Koller, A.; Nizet, V.; White, K.E.; Dixon, J.E. Dynamic Regulation of FGF23 by Fam20C Phosphorylation, GalNAc-T3 Glycosylation, and Furin Proteolysis. Proc. Natl. Acad. Sci. USA 2014, 111, 5520–5525. [Google Scholar] [CrossRef] [PubMed]
- Urakawa, I.; Yamazaki, Y.; Shimada, T.; Iijima, K.; Hasegawa, H.; Okawa, K.; Fujita, T.; Fukumoto, S.; Yamashita, T. Klotho Converts Canonical FGF Receptor into a Specific Receptor for FGF23. Nature 2006, 444, 770. [Google Scholar] [CrossRef]
- Shimada, T.; Hasegawa, H.; Yamazaki, Y.; Muto, T.; Hino, R.; Takeuchi, Y.; Fujita, T.; Nakahara, K.; Fukumoto, S.; Yamashita, T. FGF-23 is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis. J. Bone Miner. Res. 2004, 19, 429–435. [Google Scholar] [CrossRef]
- Marks, J.; Srai, S.K.; Biber, J.; Murer, H.; Unwin, R.J.; Debnam, E.S. Intestinal Phosphate Absorption and the Effect of Vitamin D: A Comparison of Rats with Mice. Exp. Physiol. 2006, 91, 531–537. [Google Scholar] [CrossRef]
- Komaba, H.; Fukagawa, M. FGF23–parathyroid Interaction: Implications in Chronic Kidney Disease. Kidney Int. 2010, 77, 292–298. [Google Scholar] [CrossRef]
- Pereira, R.C.; Jűppner, H.; Azucena-Serrano, C.E.; Yadin, O.; Salusky, I.B.; Wesseling-Perry, K. Patterns of FGF-23, DMP1, and MEPE Expression in Patients with Chronic Kidney Disease. Bone 2009, 45, 1161–1168. [Google Scholar] [CrossRef]
- Santamaría, R.; Díaz-Tocados, J.M.; de Mier, M.V.P.R.; Robles, A.; Salmerón-Rodríguez, M.D.; Ruiz, E.; Vergara, N.; Aguilera-Tejero, E.; Raya, A.; Ortega, R.; et al. Increased Phosphaturia Accelerates the Decline in Renal Function: A Search for Mechanisms. Sci. Rep. 2018, 8, 13701. [Google Scholar] [CrossRef]
- Antoniucci, D.M.; Yamashita, T.; Portale, A.A. Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men. J. Clin. Endocrinol. Metab. 2006, 91, 3144–3149. [Google Scholar] [CrossRef] [PubMed]
- Tsai, W.; Wu, H.; Peng, Y.; Hsu, S.; Chiu, Y.; Chen, H.; Yang, J.; Ko, M.; Pai, M.; Tu, Y. Effects of Lower Versus Higher Phosphate Diets on Fibroblast Growth Factor-23 Levels in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Nephrol. Dial. Transplant. 2018, 33, 1977–1983. [Google Scholar] [CrossRef] [PubMed]
- Gutierrez, O.; Isakova, T.; Rhee, E.; Shah, A.; Holmes, J.; Collerone, G.; Jüppner, H.; Wolf, M. Fibroblast Growth Factor-23 Mitigates Hyperphosphatemia but Accentuates Calcitriol Deficiency in Chronic Kidney Disease. J. Am. Soc. Nephrol. 2005, 16, 2205–2215. [Google Scholar] [CrossRef] [PubMed]
- Hasegawa, H.; Nagano, N.; Urakawa, I.; Yamazaki, Y.; Iijima, K.; Fujita, T.; Yamashita, T.; Fukumoto, S.; Shimada, T. Direct Evidence for a Causative Role of FGF23 in the Abnormal Renal Phosphate Handling and Vitamin D Metabolism in Rats with Early-Stage Chronic Kidney Disease. Kidney Int. 2010, 78, 975–980. [Google Scholar] [CrossRef]
- Komaba, H.; Fukagawa, M. The Role of FGF23 in CKD—With or without Klotho. Nat. Rev. Nephrol. 2012, 8, 484. [Google Scholar] [CrossRef]
- Hu, M.C.; Kuro-o, M.; Moe, O.W. Klotho and chronic kidney disease. Contrib. Nephrol. 2013, 180, 47–63. [Google Scholar] [CrossRef]
- Kuro-o, M. No Title. Klotho in chronic kidney disease—What’s new? Nephrol. Dial. Transplant. 2009, 24, 1705–1708. [Google Scholar] [CrossRef]
- Koh, N.; Fujimori, T.; Nishiguchi, S.; Tamori, A.; Shiomi, S.; Nakatani, T.; Sugimura, K.; Kishimoto, T.; Kinoshita, S.; Kuroki, T. Severely Reduced Production of Klotho in Human Chronic Renal Failure Kidney. Biochem. Biophys. Res. Commun. 2001, 280, 1015–1020. [Google Scholar] [CrossRef]
- Jean, G.; Terrat, J.; Vanel, T.; Hurot, J.; Lorriaux, C.; Mayor, B.; Chazot, C. High Levels of Serum Fibroblast Growth Factor (FGF)-23 are Associated with Increased Mortality in Long Haemodialysis Patients. Nephrol. Dial. Transplant. 2009, 24, 2792–2796. [Google Scholar] [CrossRef]
- Gutiérrez, O.M.; Mannstadt, M.; Isakova, T.; Rauh-Hain, J.A.; Tamez, H.; Shah, A.; Smith, K.; Lee, H.; Thadhani, R.; Jüppner, H. Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis. N. Engl. J. Med. 2008, 359, 584–592. [Google Scholar] [CrossRef] [Green Version]
- Isakova, T.; Xie, H.; Yang, W.; Xie, D.; Anderson, A.H.; Scialla, J.; Wahl, P.; Gutiérrez, O.M.; Steigerwalt, S.; He, J. Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients with Chronic Kidney Disease. JAMA 2011, 305, 2432–2439. [Google Scholar] [CrossRef] [PubMed]
- 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.-Ren. Physiol. 2010, 299, F882–F889. [Google Scholar] [CrossRef] [PubMed]
- López, I.; Rodríguez-Ortiz, M.E.; Almadén, Y.; Guerrero, F.; De Oca, A.M.; Pineda, C.; Shalhoub, V.; Rodríguez, M.; Aguilera-Tejero, E. Direct and Indirect Effects of Parathyroid Hormone on Circulating Levels of Fibroblast Growth Factor 23 in Vivo. Kidney Int. 2011, 80, 475–482. [Google Scholar] [CrossRef] [PubMed]
- Nishi, H.; Nii-Kono, T.; Nakanishi, S.; Yamazaki, Y.; Yamashita, T.; Fukumoto, S.; Ikeda, K.; Fujimori, A.; Fukagawa, M. Intravenous Calcitriol Therapy Increases Serum Concentrations of Fibroblast Growth Factor-23 in Dialysis Patients with Secondary Hyperparathyroidism. Nephron Clin. Pract. 2005, 101, c94–c99. [Google Scholar] [CrossRef] [PubMed]
- Charoenngam, N.; Rujirachun, P.; Holick, M.F.; Ungprasert, P. Oral Vitamin D 3 Supplementation Increases Serum Fibroblast Growth Factor 23 Concentration in Vitamin D-Deficient Patients: A Systematic Review and Meta-Analysis. Osteoporos. Int. 2019, 30, 2183–2193. [Google Scholar] [CrossRef] [PubMed]
- Komaba, H.; Goto, S.; Fujii, H.; Hamada, Y.; Kobayashi, A.; Shibuya, K.; Tominaga, Y.; Otsuki, N.; Nibu, K.; Nakagawa, K. Depressed Expression of Klotho and FGF Receptor 1 in Hyperplastic Parathyroid Glands from Uremic Patients. Kidney Int. 2010, 77, 232–238. [Google Scholar] [CrossRef]
- Canalejo, R.; Canalejo, A.; Martinez-Moreno, J.M.; Rodriguez-Ortiz, M.E.; Estepa, J.C.; Mendoza, F.J.; Munoz-Castaneda, J.R.; Shalhoub, V.; Almaden, Y.; Rodriguez, M. FGF23 Fails to Inhibit Uremic Parathyroid Glands. J. Am. Soc. Nephrol. 2010, 21, 1125–1135. [Google Scholar] [CrossRef] [Green Version]
- Galitzer, H.; Ben-Dov, I.Z.; Silver, J.; Naveh-Many, T. Parathyroid Cell Resistance to Fibroblast Growth Factor 23 in Secondary Hyperparathyroidism of Chronic Kidney Disease. Kidney Int. 2010, 77, 211–218. [Google Scholar] [CrossRef]
- Kendrick, J.; Cheung, A.K.; Kaufman, J.S.; Greene, T.; Roberts, W.L.; Smits, G.; Chonchol, M.; HOST Investigators. FGF-23 Associates with Death, Cardiovascular Events, and Initiation of Chronic Dialysis. J. Am. Soc. Nephrol. 2011, 22, 1913–1922. [Google Scholar] [CrossRef]
- Kestenbaum, B.; Sampson, J.N.; Rudser, K.D.; Patterson, D.J.; Seliger, S.L.; Young, B.; Sherrard, D.J.; Andress, D.L. Serum Phosphate Levels and Mortality Risk among People with Chronic Kidney Disease. J. Am. Soc. Nephrol. 2005, 16, 520–528. [Google Scholar] [CrossRef]
- Menon, V.; Greene, T.; Pereira, A.A.; Wang, X.; Beck, G.J.; Kusek, J.W.; Collins, A.J.; Levey, A.S.; Sarnak, M.J. Relationship of Phosphorus and Calcium-Phosphorus Product with Mortality in CKD. Am. J. Kidney Dis. 2005, 46, 455–463. [Google Scholar] [CrossRef] [PubMed]
- Voormolen, N.; Noordzij, M.; Grootendorst, D.C.; Beetz, I.; Sijpkens, Y.W.; Van Manen, J.G.; Boeschoten, E.W.; Huisman, R.M.; Krediet, R.T.; Dekker, F.W. High Plasma Phosphate as a Risk Factor for Decline in Renal Function and Mortality in Pre-Dialysis Patients. Nephrol. Dial. Transplant. 2007, 22, 2909–2916. [Google Scholar] [CrossRef] [PubMed]
- Eddington, H.; Hoefield, R.; Sinha, S.; Chrysochou, C.; Lane, B.; Foley, R.N.; Hegarty, J.; New, J.; O’Donoghue, D.J.; Middleton, R.J. Serum Phosphate and Mortality in Patients with Chronic Kidney Disease. Clin. J. Am. Soc. Nephrol. 2010, 5, 2251–2257. [Google Scholar] [CrossRef] [Green Version]
- Rao, M.V.; Qiu, Y.; Wang, C.; Bakris, G. Hypertension and CKD: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES), 1999–2004. Am. J. Kidney Dis. 2008, 51, S30–S37. [Google Scholar] [CrossRef] [PubMed]
- Fyfe-Johnson, A.; Alonso, A.; Selvin, E.; Bower, J.; Pankow, J.; Agarwal, S.; Lutsey, P. Serum Fibroblast Growth Factor-23 and Incident Hypertension: The Atherosclerosis Risk in Communities Study. J. Hypertens. 2016, 34, 1266–1272. [Google Scholar] [CrossRef] [PubMed]
- Akhabue, E.; Montag, S.; Reis, J.; Pool, L.; Mehta, R.; Yancy, C.; Zhao, L.; Wolf, M.; Gutierrez, O.; Carnethon, M.; et al. FGF23 (Fibroblast Growth Factor-23) and Incident Hypertension in Young and Middle-Aged Adults: The CARDIA Study. Hypertension 2018, 72, 70–76. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Shi, L.; Liu, Y.; Zhang, H.; Liu, Y.; Huang, X.; Hou, D.; Zhang, M. Plasma Fibroblast Growth Factor 23 is Elevated in Pediatric Primary Hypertension. Front. Pediatrics 2019, 7, 135. [Google Scholar] [CrossRef]
- Mendes, M.; Resende, L.; Teixeira, A.; Correia, J.; Silva, G. Blood Pressure and Phosphate Level in Diabetic and Non-Diabetic Kidney Disease: Results of the Cross-Sectional “Low Clearance Consultation” Study. Porto Biomed. J. 2017, 2, 301–305. [Google Scholar] [CrossRef]
- Mohammad, J.; Scanni, R.; Bestmann, L.; Hulter, H.N.; Krapf, R. A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects. J. Am. Soc. Nephrol. Jasn 2018, 29, 2089–2098. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.C.; Kong, J.; Wei, M.; Chen, Z.F.; Liu, S.Q.; Cao, L.P. 1,25-Dihydroxyvitamin D(3) is a Negative Endocrine Regulator of the Renin-Angiotensin System. J. Clin. Investig. 2002, 110, 229. [Google Scholar] [CrossRef]
- de Borst, M.H.; Vervloet, M.G.; ter Wee, P.M.; Navis, G. Cross Talk between the Renin-Angiotensin-Aldosterone System and Vitamin D-FGF-23-Klotho in Chronic Kidney Disease. J. Am. Soc. Nephrol. 2011, 22, 1603–1609. [Google Scholar] [CrossRef] [PubMed]
- Crackower, M.A.; Sarao, R.; Oudit, G.Y.; Yagil, C.; Kozieradzki, I.; Scanga, S.E.; Oliveira-dos-Santos, A.J.; da Costa, J.; Zhang, L.; Pei, Y. Angiotensin-Converting Enzyme 2 is an Essential Regulator of Heart Function. Nature 2002, 417, 822. [Google Scholar] [CrossRef] [PubMed]
- Dai, B.; David, V.; Martin, A.; Huang, J.; Li, H.; Jiao, Y.; Gu, W.; Quarles, L.D. A Comparative Transcriptome Analysis Identifying FGF23 Regulated Genes in the Kidney of a Mouse CKD Model. PLoS ONE 2012, 7, e44161. [Google Scholar] [CrossRef] [PubMed]
- Andrukhova, O.; Slavic, S.; Smorodchenko, A.; Zeitz, U.; Shalhoub, V.; Lanske, B.; Pohl, E.E.; Erben, R.G. FGF23 Regulates Renal Sodium Handling and Blood Pressure. Embo Mol. Med. 2014, 6, 744–759. [Google Scholar] [CrossRef]
- Patel, R.K.; Jeemon, P.; Stevens, K.K.; Mccallum, L.; Hastie, C.E.; Schneider, A.; Jardine, A.G.; Mark, P.B.; Padmanabhan, S. Association between Serum Phosphate and Calcium, Long-Term Blood Pressure, and Mortality in Treated Hypertensive Adults. J. Hypertens. 2015, 33, 2046–2053. [Google Scholar] [CrossRef]
- Bozic, M.; Panizo, S.; Sevilla, M.; Riera, M.; Soler, M.; Pascual, J.; Lopez, I.; Freixenet, M.; Fernandez, E.; Valdivielso, J. High Phosphate Diet Increases Arterial Blood Pressure Via a Parathyroid Hormone Mediated Increase of Renin. J. Hypertens. 2014, 32, 1822–1832. [Google Scholar] [CrossRef]
- Suzuki, Y.; Mitsushima, S.; Kato, A.; Yamaguchi, T.; Ichihara, S. High-Phosphorus/Zinc-Free Diet Aggravates Hypertension and Cardiac Dysfunction in a Rat Model of the Metabolic Syndrome. Cardiovasc. Pathol. 2014, 23, 43–49. [Google Scholar] [CrossRef]
- Mizuno, M.; Mitchell, J.H.; Crawford, S.; Huang, C.; Maalouf, N.; Hu, M.; Moe, O.W.; Smith, S.A.; Vongpatanasin, W. High Dietary Phosphate Intake Induces Hypertension and Augments Exercise Pressor Reflex Function in Rats. American journal of physiology. Regul. Integr. Comp. Physiol. 2016, 311, R39–R48. [Google Scholar] [CrossRef]
- Delaney, E.P.; Greaney, J.L.; Edwards, D.G.; Rose, W.C.; Fadel, P.J.; Farquhar, W.B. Exaggerated Sympathetic and Pressor Responses to Handgrip Exercise in Older Hypertensive Humans: Role of the Muscle Metaboreflex. Am. J. Physiol.-Heart Circ. Physiol. 2010, 299, H1318–H1327. [Google Scholar] [CrossRef]
- Vongpatanasin, W.; Wang, Z.; Arbique, D.; Arbique, G.; Adams-Huet, B.; Mitchell, J.H.; Victor, R.G.; Thomas, G.D. Functional Sympatholysis is Impaired in Hypertensive Humans. J. Physiol. (Lond.) 2011, 589, 1209–1220. [Google Scholar] [CrossRef]
- Goodman, W.G.; Goldin, J.; Kuizon, B.D.; Yoon, C.; Gales, B.; Sider, D.; Wang, Y.; Chung, J.; Emerick, A.; Greaser, L. Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who are Undergoing Dialysis. N. Engl. J. Med. 2000, 342, 1478–1483. [Google Scholar] [CrossRef] [PubMed]
- Blacher, J.; Guerin, A.P.; Pannier, B.; Marchais, S.J.; London, G.M. Arterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease. Hypertension 2001, 38, 938–942. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Russo, D.; Corrao, S.; Battaglia, Y.; Andreucci, M.; Caiazza, A.; Carlomagno, A.; Lamberti, M.; Pezone, N.; Pota, A.; Russo, L. Progression of Coronary Artery Calcification and Cardiac Events in Patients with Chronic Renal Disease Not Receiving Dialysis. Kidney Int. 2011, 80, 112–118. [Google Scholar] [CrossRef] [PubMed]
- Nasrallah, M.M.; El-Shehaby, A.R.; Salem, M.M.; Osman, N.A.; El Sheikh, E.; Sharaf El Din, U.A. Fibroblast Growth Factor-23 (FGF-23) is Independently Correlated to Aortic Calcification in Haemodialysis Patients. Nephrol. Dial. Transplant. 2010, 25, 2679–2685. [Google Scholar] [CrossRef]
- Desjardins, L.; Liabeuf, S.; Renard, C.; Lenglet, A.; Lemke, H.D.; Choukroun, G.; Drueke, T.B.; Massy, Z.A.; European Uremic Toxin (EUTox) Work Group. FGF23 is Independently Associated with Vascular Calcification but Not Bone Mineral Density in Patients at various CKD Stages. Osteoporos Int. 2012, 23, 2017–2025. [Google Scholar]
- Scialla, J.J.; Lau, W.L.; Reilly, M.P.; Isakova, T.; Yang, H.; Crouthamel, M.H.; Chavkin, N.W.; Rahman, M.; Wahl, P.; Amaral, A.P. Fibroblast Growth Factor 23 is Not Associated with and does Not Induce Arterial Calcification. Kidney Int. 2013, 83, 1159–1168. [Google Scholar] [CrossRef]
- Lindberg, K.; Olauson, H.; Amin, R.; Ponnusamy, A.; Goetz, R.; Taylor, R.F.; Mohammadi, M.; Canfield, A.; Kublickiene, K.; Larsson, T.E. Arterial Klotho Expression and FGF23 Effects on Vascular Calcification and Function. PLoS ONE 2013, 8, e60658. [Google Scholar] [CrossRef]
- Lim, K.; Lu, T.; Molostvov, G.; Lee, C.; Lam, F.T.; Zehnder, D.; Hsiao, L. Vascular Klotho Deficiency Potentiates the Development of Human Artery Calcification and Mediates Resistance to Fibroblast Growth Factor 23. Circulation 2012, 125, 2243–2255. [Google Scholar] [CrossRef] [Green Version]
- Zhu, D.; Mackenzie, N.C.; Millan, J.L.; Farquharson, C.; MacRae, V.E. A Protective Role for FGF-23 in Local Defence against Disrupted Arterial Wall Integrity? Mol. Cell. Endocrinol. 2013, 372, 1–11. [Google Scholar] [CrossRef]
- Jimbo, R.; Kawakami-Mori, F.; Mu, S.; Hirohama, D.; Majtan, B.; Shimizu, Y.; Yatomi, Y.; Fukumoto, S.; Fujita, T.; Shimosawa, T. Fibroblast Growth Factor 23 Accelerates Phosphate-Induced Vascular Calcification in the Absence of Klotho Deficiency. Kidney Int. 2014, 85, 1103–1111. [Google Scholar] [CrossRef]
- Chen, Y.; Huang, C.; Duan, Z.; Xu, C.; Chen, Y. Klotho/FGF23 Axis Mediates High Phosphate-induced Vascular Calcification in Vascular Smooth Muscle Cells Via Wnt7b/Β-catenin Pathway. Kaohsiung J. Med. Sci. 2019, 35, 393–400. [Google Scholar] [CrossRef] [PubMed]
- Shigematsu, T.; Kono, T.; Satoh, K.; Yokoyama, K.; Yoshida, T.; Hosoya, T.; Shirai, K. Phosphate Overload Accelerates Vascular Calcium Deposition in End-stage Renal Disease Patients. Nephrol. Dial. Transplant. 2003, 18, iii86–iii89. [Google Scholar] [CrossRef] [PubMed]
- Adeney, K.L.; Siscovick, D.S.; Ix, J.H.; Seliger, S.L.; Shlipak, M.G.; Jenny, N.S.; Kestenbaum, B.R. Association of Serum Phosphate with Vascular and Valvular Calcification in Moderate CKD. J. Am. Soc. Nephrol. 2009, 20, 381–387. [Google Scholar] [CrossRef] [PubMed]
- El-Abbadi, M.M.; Pai, A.S.; Leaf, E.M.; Yang, H.; Bartley, B.A.; Quan, K.K.; Ingalls, C.M.; Liao, H.W.; Giachelli, C.M. Phosphate Feeding Induces Arterial Medial Calcification in Uremic Mice: Role of Serum Phosphorus, Fibroblast Growth Factor-23, and Osteopontin. Kidney Int. 2009, 75, 1297–1307. [Google Scholar] [CrossRef] [PubMed]
- Lau, W.L.; Linnes, M.; Chu, E.Y.; Foster, B.L.; Bartley, B.A.; Somerman, M.J.; Giachelli, C.M. High Phosphate Feeding Promotes Mineral and Bone Abnormalities in Mice with Chronic Kidney Disease. Nephrol. Dial. Transplant. 2012, 28, 62–69. [Google Scholar] [CrossRef] [PubMed]
- Shroff, R.C.; McNair, R.; Skepper, J.N.; Figg, N.; Schurgers, L.J.; Deanfield, J.; Rees, L.; Shanahan, C.M. Chronic Mineral Dysregulation Promotes Vascular Smooth Muscle Cell Adaptation and Extracellular Matrix Calcification. J. Am. Soc. Nephrol. 2010, 21, 103–112. [Google Scholar] [CrossRef]
- Collins, J.F.; Bai, L.; Ghishan, F.K. The SLC20 Family of Proteins: Dual Functions as Sodium-Phosphate Cotransporters and Viral Receptors. Pflügers Arch. 2004, 447, 647–652. [Google Scholar] [CrossRef]
- Li, X.; Yang, H.; Giachelli, C.M. Role of the Sodium-Dependent Phosphate Cotransporter, Pit-1, in Vascular Smooth Muscle Cell Calcification. Circ. Res. 2006, 98, 905–912. [Google Scholar] [CrossRef] [Green Version]
- Chavkin, N.W.; Chia, J.J.; Crouthamel, M.H.; Giachelli, C.M. Phosphate Uptake-Independent Signaling Functions of the Type III Sodium-Dependent Phosphate Transporter, PiT-1, in Vascular Smooth Muscle Cells. Exp. Cell Res. 2015, 333, 39–48. [Google Scholar] [CrossRef]
- Yamada, S.; Leaf, E.M.; Chia, J.J.; Cox, T.C.; Speer, M.Y.; Giachelli, C.M. PiT-2, a Type III Sodium-Dependent Phosphate Transporter, Protects Against Vascular Calcification in Mice with Chronic Kidney Disease Fed a High-Phosphate Diet. Kidney Int. 2018, 94, 716–727. [Google Scholar] [CrossRef]
- Reynolds, J.L.; Joannides, A.J.; Skepper, J.N.; McNair, R.; Schurgers, L.J.; Proudfoot, D.; Jahnen-Dechent, W.; Weissberg, P.L.; Shanahan, C.M. Human Vascular Smooth Muscle Cells Undergo Vesicle-Mediated Calcification in Response to Changes in Extracellular Calcium and Phosphate Concentrations: A Potential Mechanism for Accelerated Vascular Calcification in ESRD. J. Am. Soc. Nephrol. 2004, 15, 2857–2867. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Speer, M.Y.; Li, X.; Hiremath, P.G.; Giachelli, C.M. Runx2/Cbfa1, but Not Loss of Myocardin, is Required for Smooth Muscle Cell Lineage Reprogramming Toward Osteochondrogenesis. J. Cell. Biochem. 2010, 110, 935–947. [Google Scholar] [CrossRef] [PubMed]
- Chen, N.X.; O’Neill, K.D.; Duan, D.; Moe, S.M. Phosphorus and Uremic Serum Up-Regulate Osteopontin Expression in Vascular Smooth Muscle Cells. Kidney Int. 2002, 62, 1724–1731. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Yang, H.; Giachelli, C.M. BMP-2 Promotes Phosphate Uptake, Phenotypic Modulation, and Calcification of Human Vascular Smooth Muscle Cells. Atherosclerosis 2008, 199, 271–277. [Google Scholar] [CrossRef]
- Steitz, S.A.; Speer, M.Y.; Curinga, G.; Yang, H.; Haynes, P.; Aebersold, R.; Schinke, T.; Karsenty, G.; Giachelli, C.M. Smooth Muscle Cell Phenotypic Transition Associated with Calcification: Upregulation of Cbfa1 and Downregulation of Smooth Muscle Lineage Markers. Circ. Res. 2001, 89, 1147–1154. [Google Scholar] [CrossRef]
- Shanahan, C.M.; Crouthamel, M.H.; Kapustin, A.; Giachelli, C.M. Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate. Circ. Res. 2011, 109, 697–711. [Google Scholar] [CrossRef] [Green Version]
- Boström, K.I.; Rajamannan, N.M.; Towler, D.A. The Regulation of Valvular and Vascular Sclerosis by Osteogenic Morphogens. Circ. Res. 2011, 109, 564–577. [Google Scholar] [CrossRef]
- Cheng, L.; Zhang, L.; Yang, J.; Hao, L. Activation of Peroxisome Proliferator-Activated Receptor Γ Inhibits Vascular Calcification by Upregulating Klotho. Exp. Ther. Med. 2017, 13, 467–474. [Google Scholar] [CrossRef]
- Liu, C.; Liu, Y.; Liu, L.; Zhang, J.; Zhang, Y.; Zhang, B.; Zhang, Z.; Bi, X.; Nie, L.; Xiong, J.; et al. High Phosphate-Induced Downregulation of PPARγ Contributes to CKD-Associated Vascular Calcification. J. Mol. Cell. Cardiol. 2018, 114, 264–275. [Google Scholar] [CrossRef]
- Mihai, S.; Codrici, E.; Popescu, I.D.; Enciu, A.; Albulescu, L.; Necula, L.G.; Mambet, C.; Anton, G.; Tanase, C. Inflammation-Related Mechanisms in Chronic Kidney Disease Prediction, Progression, and Outcome. J. Immunol. Res. 2018, 2018, 2180373. [Google Scholar] [CrossRef]
- Hénaut, L.; Massy, Z.A. New Insights into the Key Role of Interleukin 6 in Vascular Calcification of Chronic Kidney Disease. Nephrol. Dial. Transplant. 2018, 33, 543–548. [Google Scholar] [CrossRef]
- Mendoza, J.M.; Isakova, T.; Ricardo, A.C.; Xie, H.; Navaneethan, S.D.; Anderson, A.H.; Bazzano, L.A.; Xie, D.; Kretzler, M.; Nessel, L. Fibroblast Growth Factor 23 and Inflammation in CKD. Clin. J. Am. Soc. Nephrol. 2012, 7, 1155–1162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hanks, L.J.; Casazza, K.; Judd, S.E.; Jenny, N.S.; Gutiérrez, O.M. Associations of Fibroblast Growth Factor-23 with Markers of Inflammation, Insulin Resistance and Obesity in Adults. PLoS ONE 2015, 10, e0122885. [Google Scholar] [CrossRef]
- Wallquist, C.; Mansouri, L.; Norrbäck, M.; Hylander, B.; Jacobson, S.H.; Larsson, T.E.; Lundahl, J. Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease. Nephron 2018, 138, 287–295. [Google Scholar] [CrossRef] [Green Version]
- David, V.; Martin, A.; Isakova, T.; Spaulding, C.; Qi, L.; Ramirez, V.; Zumbrennen-Bullough, K.B.; Sun, C.C.; Lin, H.Y.; Babitt, J.L. Inflammation and Functional Iron Deficiency Regulate Fibroblast Growth Factor 23 Production. Kidney Int. 2016, 89, 135–146. [Google Scholar] [CrossRef] [PubMed]
- Durlacher-Betzer, K.; Hassan, A.; Levi, R.; Axelrod, J.; Silver, J.; Naveh-Many, T. Interleukin-6 Contributes to the Increase in Fibroblast Growth Factor 23 Expression in Acute and Chronic Kidney Disease. Kidney Int. 2018, 94, 315–325. [Google Scholar] [CrossRef] [PubMed]
- Egli-Spichtig, D.; Silva, P.H.I.; Glaudemans, B.; Gehring, N.; Bettoni, C.; Zhang, M.; Arroyo, E.P.; Schönenberger, D.; Rajski, M.; Hoogewijis, D. Tumor Necrosis Factor Stimulates Fibroblast Growth Factor 23 Levels in Chronic Kidney Disease and Non-Renal Inflammation. Kidney Int. 2019, 96, 890–905. [Google Scholar] [CrossRef] [PubMed]
- Han, X.; Li, L.; Yang, J.; King, G.; Xiao, Z.; Quarles, L.D. Counter-regulatory Paracrine Actions of FGF-23 and 1,25 (OH) 2D in Macrophages. Febs Lett. 2016, 590, 53–67. [Google Scholar] [CrossRef]
- Singh, S.; Grabner, A.; Yanucil, C.; Schramm, K.; Czaya, B.; Krick, S.; Czaja, M.J.; Bartz, R.; Abraham, R.; Di Marco, G.S. Fibroblast Growth Factor 23 Directly Targets Hepatocytes to Promote Inflammation in Chronic Kidney Disease. Kidney Int. 2016, 90, 985–996. [Google Scholar] [CrossRef]
- Aghagolzadeh, P.; Bachtler, M.; Bijarnia, R.; Jackson, C.; Smith, E.R.; Odermatt, A.; Radpour, R.; Pasch, A. Calcification of Vascular Smooth Muscle Cells is Induced by Secondary Calciprotein Particles and Enhanced by Tumor Necrosis Factor-A. Atherosclerosis 2016, 251, 404–414. [Google Scholar] [CrossRef]
- Pazár, B.; Ea, H.; Narayan, S.; Kolly, L.; Bagnoud, N.; Chobaz, V.; Roger, T.; Lioté, F.; So, A.; Busso, N. Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome in Vitro. J. Immunol. 2011, 186, 2495–2502. [Google Scholar] [CrossRef] [PubMed]
- Tintut, Y.; Patel, J.; Parhami, F.; Demer, L.L. Tumor Necrosis Factor-A Promotes in Vitro Calcification of Vascular Cells Via the cAMP Pathway. Circulation 2000, 102, 2636–2642. [Google Scholar] [CrossRef] [PubMed]
- Awan, Z.; Denis, M.; Roubtsova, A.; Essalmani, R.; Marcinkiewicz, J.; Awan, A.; Gram, H.; Seidah, N.G.; Genest, J. Reducing Vascular Calcification by Anti-IL-1β Monoclonal Antibody in a Mouse Model of Familial Hypercholesterolemia. Angiology 2016, 67, 157–167. [Google Scholar] [CrossRef] [PubMed]
- Ceneri, N.; Zhao, L.; Young, B.D.; Healy, A.; Coskun, S.; Vasavada, H.; Yarovinsky, T.O.; Ike, K.; Pardi, R.; Qin, L. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production. Arterioscler. Thromb. Vasc. Biol. 2017, 37, 328–340. [Google Scholar] [CrossRef] [PubMed]
- Bhatnagar, S.; Panguluri, S.K.; Gupta, S.K.; Dahiya, S.; Lundy, R.F.; Kumar, A. Tumor Necrosis Factor-A Regulates Distinct Molecular Pathways and Gene Networks in Cultured Skeletal Muscle Cells. PLoS ONE 2010, 5, e13262. [Google Scholar] [CrossRef]
- Azpiazu, D.; Gonzalo, S.; Villa-Bellosta, R. Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target. Curr. Cardiol. Rev. 2019, 15, 91–95. [Google Scholar] [CrossRef]
- Zickler, D.; Luecht, C.; Willy, K.; Chen, L.; Witowski, J.; Girndt, M.; Fiedler, R.; Storr, M.; Kamhieh-Milz, J.; Schoon, J. Tumour Necrosis Factor-Alpha in Uraemic Serum Promotes Osteoblastic Transition and Calcification of Vascular Smooth Muscle Cells Via Extracellular Signal-Regulated Kinases and Activator Protein 1/C-FOS-Mediated Induction of Interleukin 6 Expression. Nephrol. Dial. Transplant. 2017, 33, 574–585. [Google Scholar] [CrossRef]
- Agharazii, M.; St-Louis, R.; Gautier-Bastien, A.; Ung, R.; Mokas, S.; Larivière, R.; Richard, D.E. Inflammatory Cytokines and Reactive Oxygen Species as Mediators of Chronic Kidney Disease-Related Vascular Calcification. Am. J. Hypertens. 2014, 28, 746–755. [Google Scholar] [CrossRef] [Green Version]
- Reynolds, J.L.; Skepper, J.N.; McNair, R.; Kasama, T.; Gupta, K.; Weissberg, P.L.; Jahnen-Dechent, W.; Shanahan, C.M. Multifunctional Roles for Serum Protein Fetuin-a in Inhibition of Human Vascular Smooth Muscle Cell Calcification. J. Am. Soc. Nephrol. 2005, 16, 2920–2930. [Google Scholar] [CrossRef] [PubMed]
- Levin, A.; Thompson, C.R.; Ethier, J.; Carlisle, E.J.; Tobe, S.; Mendelssohn, D.; Burgess, E.; Jindal, K.; Barrett, B.; Singer, J. Left Ventricular Mass Index Increase in Early Renal Disease: Impact of Decline in Hemoglobin. Am. J. Kidney Dis. 1999, 34, 125–134. [Google Scholar] [CrossRef]
- Foley, R.N.; Parfrey, P.S.; Harnett, J.D.; Kent, G.M.; Martin, C.J.; Murray, D.C.; Barre, P.E. Clinical and Echocardiographic Disease in Patients Starting End-Stage Renal Disease Therapy. Kidney Int. 1995, 47, 186–192. [Google Scholar] [CrossRef] [PubMed]
- Paoletti, E.; Bellino, D.; Cassottana, P.; Rolla, D.; Cannella, G. Left Ventricular Hypertrophy in Nondiabetic Predialysis CKD. Am. J. Kidney Dis. 2005, 46, 320–327. [Google Scholar] [CrossRef] [PubMed]
- Hsu, H.J.; Wu, M. Fibroblast Growth Factor 23: A Possible Cause of Left Ventricular Hypertrophy in Hemodialysis Patients. Am. J. Med. Sci. 2009, 337, 116–122. [Google Scholar] [CrossRef] [PubMed]
- Mirza, M.A.; Larsson, A.; Melhus, H.; Lind, L.; Larsson, T.E. Serum Intact FGF23 Associate with Left Ventricular Mass, Hypertrophy and Geometry in an Elderly Population. Atherosclerosis 2009, 207, 546–551. [Google Scholar] [CrossRef]
- Kirkpantur, A.; Balci, M.; Gurbuz, O.A.; Afsar, B.; Canbakan, B.; Akdemir, R.; Ayli, M.D. Serum Fibroblast Growth Factor-23 (FGF-23) Levels are Independently Associated with Left Ventricular Mass and Myocardial Performance Index in Maintenance Haemodialysis Patients. Nephrol. Dial. Transplant. 2011, 26, 1346–1354. [Google Scholar] [CrossRef]
- Negishi, K.; Kobayashi, M.; Ochiai, I.; Yamazaki, Y.; Hasegawa, H.; Yamashita, T.; Shimizu, T.; Kasama, S.; Kurabayashi, M. Association between Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Maintenance Hemodialysis Patients. Circ. J. 2010, 74, 2734–2740. [Google Scholar] [CrossRef]
- Seeherunvong, W.; Abitbol, C.; Chandar, J.; Rusconi, P.; Zilleruelo, G.; Freundlich, M. Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Children on Dialysis. Pediatr. Nephrol. 2012, 27, 2129–2136. [Google Scholar] [CrossRef]
- Mitsnefes, M.M.; Betoko, A.; Schneider, M.F.; Salusky, I.B.; Wolf, M.S.; Jüppner, H.; Warady, B.A.; Furth, S.L.; Portale, A.A. FGF23 and Left Ventricular Hypertrophy in Children with CKD. Clin. J. Am. Soc. Nephrol. Cjasn 2018, 13, 45–52. [Google Scholar] [CrossRef]
- Leifheit-Nestler, M.; große Siemer, R.; Flasbart, K.; Richter, B.; Kirchhoff, F.; Ziegler, W.H.; Klintschar, M.; Becker, J.U.; Erbersdobler, A.; Aufricht, C. Induction of Cardiac FGF23/FGFR4 Expression is Associated with Left Ventricular Hypertrophy in Patients with Chronic Kidney Disease. Nephrol. Dial. Transplant. 2015, 31, 1088–1099. [Google Scholar] [CrossRef]
- Faul, C.; Amaral, A.P.; Oskouei, B.; Hu, M.; Sloan, A.; Isakova, T.; Gutiérrez, O.M.; Aguillon-Prada, R.; Lincoln, J.; Hare, J.M.; et al. FGF23 Induces Left Ventricular Hypertrophy. J. Clin. Investig. 2011, 121, 4393–4408. [Google Scholar] [CrossRef]
- Grabner, A.; Amaral, A.P.; Schramm, K.; Singh, S.; Sloan, A.; Yanucil, C.; Li, J.; Shehadeh, L.A.; Hare, J.M.; David, V. Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab. 2015, 22, 1020–1032. [Google Scholar] [CrossRef] [Green Version]
- Di Marco, G.S.; Reuter, S.; Kentrup, D.; Grabner, A.; Amaral, A.P.; Fobker, M.; Stypmann, J.; Pavenstädt, H.; Wolf, M.; Faul, C. Treatment of Established Left Ventricular Hypertrophy with Fibroblast Growth Factor Receptor Blockade in an Animal Model of CKD. Nephrol. Dial. Transplant. 2014, 29, 2028–2035. [Google Scholar] [CrossRef]
- Molkentin, J.D. Calcineurin–NFAT Signaling Regulates the Cardiac Hypertrophic Response in Coordination with the MAPKs. Cardiovasc. Res. 2004, 63, 467–475. [Google Scholar] [CrossRef]
- Takashi, Y.; Kinoshita, Y.; Hori, M.; Ito, N.; Taguchi, M.; Fukumoto, S. Patients with FGF23-Related Hypophosphatemic Rickets/Osteomalacia do Not Present with Left Ventricular Hypertrophy. Endocr. Res. 2017, 42, 132–137. [Google Scholar] [CrossRef]
- Leifheit-Nestler, M.; Richter, B.; Basaran, M.; Nespor, J.; Vogt, I.; Alesutan, I.; Voelkl, J.; Lang, F.; Heineke, J.; Krick, S. Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23. Front. Endocrinol. 2018, 9, 333. [Google Scholar] [CrossRef]
- Pastor-Arroyo, E.; Gehring, N.; Krudewig, C.; Costantino, S.; Bettoni, C.; Knöpfel, T.; Sabrautzki, S.; Lorenz-Depiereux, B.; Pastor, J.; Strom, T.M. The Elevation of Circulating Fibroblast Growth Factor 23 without Kidney Disease does Not Increase Cardiovascular Disease Risk. Kidney Int. 2018, 94, 49–59. [Google Scholar] [CrossRef]
- Faul, C. FGF23 Effects on the Heart—Levels, Time, Source, And context Matter. Kidney Int. 2018, 94, 7–11. [Google Scholar] [CrossRef]
- Foley, R.N.; Collins, A.J.; Herzog, C.A.; Ishani, A.; Kalra, P.A. Serum Phosphate and Left Ventricular Hypertrophy in Young Adults: The Coronary Artery Risk Development in Young Adults Study. Kidney Blood Press. Res. 2009, 32, 37–44. [Google Scholar] [CrossRef]
- Saab, G.; Whooley, M.A.; Schiller, N.B.; Ix, J.H. Association of Serum Phosphorus with Left Ventricular Mass in Men and Women with Stable Cardiovascular Disease: Data from the Heart and Soul Study. Am. J. Kidney Dis. 2010, 56, 496–505. [Google Scholar] [CrossRef]
- Chue, C.D.; Edwards, N.C.; Moody, W.E.; Steeds, R.P.; Townend, J.N.; Ferro, C.J. Serum Phosphate is Associated with Left Ventricular Mass in Patients with Chronic Kidney Disease: A Cardiac Magnetic Resonance Study. Heart 2012, 98, 219–224. [Google Scholar] [CrossRef]
- Yamamoto, K.T.; Robinson-Cohen, C.; De Oliveira, M.C.; Kostina, A.; Nettleton, J.A.; Ix, J.H.; Nguyen, H.; Eng, J.; Lima, J.A.; Siscovick, D.S. Dietary Phosphorus is Associated with Greater Left Ventricular Mass. Kidney Int. 2013, 83, 707–714. [Google Scholar] [CrossRef]
- Zou, J.; Yu, Y.; Wu, P.; Lin, F.; Yao, Y.; Xie, Y.; Jiang, G. Serum Phosphorus is Related to Left Ventricular Remodeling Independent of Renal Function in Hospitalized Patients with Chronic Kidney Disease. Int. J. Cardiol. 2016, 221, 134–140. [Google Scholar] [CrossRef]
- Amann, K.; Törnig, J.; Kugel, B.; Gross, M.; Tyralla, K.; El-Shakmak, A.; Szabo, A.; Ritz, E. Hyperphosphatemia Aggravates Cardiac Fibrosis and Microvascular Disease in Experimental Uremia. Kidney Int. 2003, 63, 1296–1301. [Google Scholar] [CrossRef]
- Neves, K.R.; Graciolli, F.G.; Dos Reis, L.M.; Pasqualucci, C.A.; Moyses, R.M.; Jorgetti, V. Adverse Effects of Hyperphosphatemia on Myocardial Hypertrophy, Renal Function, and Bone in Rats with Renal Failure. Kidney Int. 2004, 66, 2237–2244. [Google Scholar] [CrossRef]
- Peri-Okonny, P.; Baskin, K.K.; Iwamoto, G.; Mitchell, J.H.; Smith, S.A.; Kim, H.K.; Szweda, L.I.; Bassel-Duby, R.; Fujikawa, T.; Castorena, C.M. High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice. Circulation 2019, 139, 1422–1434. [Google Scholar] [CrossRef]
- Hu, M.C.; Shi, M.; Cho, H.J.; Adams-Huet, B.; Paek, J.; Hill, K.; Shelton, J.; Amaral, A.P.; Faul, C.; Taniguchi, M. Klotho and Phosphate are Modulators of Pathologic Uremic Cardiac Remodeling. J. Am. Soc. Nephrol. 2015, 26, 1290–1302. [Google Scholar] [CrossRef]
- Hu, M.C.; Scanni, R.; Ye, J.; Zhang, J.; Shi, M.; Maique, J.; Flores, B.; Moe, O.W.; Krapf, R. Dietary Vitamin D Interacts with High Phosphate–induced Cardiac Remodeling in Rats with Normal Renal Function. Nephrol. Dial. Transplant. 2019, gfz156. [Google Scholar] [CrossRef]
- Liu, Y.; Huang, C.; Chang, C.; Chou, C.; Lin, S.; Wang, I.; Hsieh, D.J.; Jong, G.; Huang, C.; Wang, C. Hyperphosphate-Induced Myocardial Hypertrophy through the GATA-4/NFAT-3 Signaling Pathway is Attenuated by ERK Inhibitor Treatment. Cardiorenal Med. 2015, 5, 79–88. [Google Scholar] [CrossRef]
- Ferrari, S.L.; Bonjour, J.; Rizzoli, R. Fibroblast Growth Factor-23 Relationship to Dietary Phosphate and Renal Phosphate Handling in Healthy Young Men. J. Clin. Endocrinol. Metab. 2005, 90, 1519–1524. [Google Scholar] [CrossRef] [Green Version]
- Burnett, S.M.; Gunawardene, S.C.; Bringhurst, F.R.; Jüppner, H.; Lee, H.; Finkelstein, J.S. Regulation of C-terminal and Intact FGF-23 by Dietary Phosphate in Men and Women. J. Bone Miner. Res. 2006, 21, 1187–1196. [Google Scholar] [CrossRef]
- Tsai, W.; Wu, H.; Peng, Y.; Hsu, S.; Chiu, Y.; Yang, J.; Chen, H.; Pai, M.; Lin, W.; Hung, K. Short-Term Effects of very-Low-Phosphate and Low-Phosphate Diets on Fibroblast Growth Factor 23 in Hemodialysis Patients: A Randomized Crossover Trial. Clin. J. Am. Soc. Nephrol. 2019, 14, 1475–1483. [Google Scholar] [CrossRef] [PubMed]
- Kalantar-Zadeh, K.; Gutekunst, L.; Mehrotra, R.; Kovesdy, C.P.; Bross, R.; Shinaberger, C.S.; Noori, N.; Hirschberg, R.; Benner, D.; Nissenson, A.R. Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease. Clin. J. Am. Soc. Nephrol. 2010, 5, 519–530. [Google Scholar] [CrossRef] [PubMed]
- Moe, S.M.; Chen, N.X.; Seifert, M.F.; Sinders, R.M.; Duan, D.; Chen, X.; Liang, Y.; Radcliff, J.S.; White, K.E.; Gattone II, V.H. A Rat Model of Chronic Kidney Disease-Mineral Bone Disorder. Kidney Int. 2009, 75, 176–184. [Google Scholar] [CrossRef] [PubMed]
- Moe, S.M.; Zidehsarai, M.P.; Chambers, M.A.; Jackman, L.A.; Radcliffe, J.S.; Trevino, L.L.; Donahue, S.E.; Asplin, J.R. Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease. Clin. J. Am. Soc. Nephrol. 2011, 6, 257–264. [Google Scholar] [CrossRef] [PubMed]
- Scialla, J.J.; Appel, L.J.; Wolf, M.; Yang, W.; Zhang, X.; Sozio, S.M.; Miller, E.R., III; Bazzano, L.A.; Cuevas, M.; Glenn, M.J. Plant Protein Intake is Associated with Fibroblast Growth Factor 23 and Serum Bicarbonate Levels in Patients with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Study. J. Ren. Nutr. 2012, 22, 37–388. [Google Scholar] [CrossRef]
- Sullivan, C.; Sayre, S.S.; Leon, J.B.; Machekano, R.; Love, T.E.; Porter, D.; Marbury, M.; Sehgal, A.R. Effect of Food Additives on Hyperphosphatemia among Patients with End-Stage Renal Disease: A Randomized Controlled Trial. JAMA 2009, 301, 629–635. [Google Scholar] [CrossRef]
- de Fornasari, M.L.L.; dos Santos Sens, Y.A. Replacing Phosphorus-Containing Food Additives with Foods without Additives Reduces Phosphatemia in End-Stage Renal Disease Patients: A Randomized Clinical Trial. J. Ren. Nutr. 2017, 27, 97–105. [Google Scholar] [CrossRef]
- Shinaberger, C.S.; Greenland, S.; Kopple, J.D.; Van Wyck, D.; Mehrotra, R.; Kovesdy, C.P.; Kalantar-Zadeh, K. Is Controlling Phosphorus by Decreasing Dietary Protein Intake Beneficial Or Harmful in Persons with Chronic Kidney Disease? Am. J. Clin. Nutr. 2008, 88, 1511–1518. [Google Scholar] [CrossRef]
- Di Iorio, B.; Di Micco, L.; Torraca, S.; Sirico, M.L.; Russo, L.; Pota, A.; Mirenghi, F.; Russo, D. Acute Effects of very-Low-Protein Diet on FGF23 Levels: A Randomized Study. Clin. J. Am. Soc. Nephrol. 2012, 7, 581–587. [Google Scholar] [CrossRef]
- Oliveira, R.B.; Cancela, A.L.; Graciolli, F.G.; Dos Reis, L.M.; Draibe, S.A.; Cuppari, L.; Carvalho, A.B.; Jorgetti, V.; Canziani, M.E.; Moysés, R.M. Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy? Clin. J. Am. Soc. Nephrol. 2010, 5, 286–291. [Google Scholar] [CrossRef]
- Block, G.A.; Wheeler, D.C.; Persky, M.S.; Kestenbaum, B.; Ketteler, M.; Spiegel, D.M.; Allison, M.A.; Asplin, J.; Smits, G.; Hoofnagle, A.N. Effects of Phosphate Binders in Moderate CKD. J. Am. Soc. Nephrol. 2012, 23, 1407–1415. [Google Scholar] [CrossRef] [PubMed]
- Patel, L.; Bernard, L.M.; Elder, G.J. Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials. Clin. J. Am. Soc. Nephrol. 2016, 11, 232–244. [Google Scholar] [CrossRef] [PubMed]
- Yokoyama, K.; Hirakata, H.; Akiba, T.; Fukagawa, M.; Nakayama, M.; Sawada, K.; Kumagai, Y.; Block, G.A. Ferric Citrate Hydrate for the Treatment of Hyperphosphatemia in Nondialysis-Dependent CKD. Clin. J. Am. Soc. Nephrol. 2014, 9, 543–552. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gonzalez-Parra, E.; Gonzalez-Casaus, M.L.; Galán, A.; Martinez-Calero, A.; Navas, V.; Rodriguez, M.; Ortiz, A. Lanthanum Carbonate Reduces FGF23 in Chronic Kidney Disease Stage 3 Patients. Nephrol. Dial. Transplant. 2011, 26, 2567–2571. [Google Scholar] [CrossRef] [PubMed]
- Isakova, T.; Barchi-Chung, A.; Enfield, G.; Smith, K.; Vargas, G.; Houston, J.; Xie, H.; Wahl, P.; Schiavenato, E.; Dosch, A. Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD. Clin. J. Am. Soc. Nephrol. 2013, 8, 1009–1018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jamal, S.A.; Vandermeer, B.; Raggi, P.; Mendelssohn, D.C.; Chatterley, T.; Dorgan, M.; Lok, C.E.; Fitchett, D.; Tsuyuki, R.T. Effect of Calcium-Based Versus Non-Calcium-Based Phosphate Binders on Mortality in Patients with Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis. Lancet 2013, 382, 1268–1277. [Google Scholar] [CrossRef]
- Block, G.A.; Pergola, P.E.; Fishbane, S.; Martins, J.G.; LeWinter, R.D.; Uhlig, K.; Neylan, J.F.; Chertow, G.M. Effect of Ferric Citrate on Serum Phosphate and Fibroblast Growth Factor 23 among Patients with Nondialysis-Dependent Chronic Kidney Disease: Path Analyses. Nephrol. Dial. Transplant. 2018, 34, 1115–1124. [Google Scholar] [CrossRef]
- Block, G.A.; Block, M.S.; Smits, G.; Mehta, R.; Isakova, T.; Wolf, M.; Chertow, G.M. A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD. J. Am. Soc. Nephrol. 2019, 30, 1495–1504. [Google Scholar] [CrossRef] [Green Version]
- Francis, C.; Courbon, G.; Gerber, C.; Neuburg, S.; Wang, X.; Dussold, C.; Capella, M.; Qi, L.; Isakova, T.; Mehta, R. Ferric Citrate Reduces Fibroblast Growth Factor 23 Levels and Improves Renal and Cardiac Function in a Mouse Model of Chronic Kidney Disease. Kidney Int. 2019, in press. [Google Scholar] [CrossRef]
- Ix, J.H.; Isakova, T.; Larive, B.; Raphael, K.L.; Raj, D.S.; Cheung, A.K.; Sprague, S.M.; Fried, L.F.; Gassman, J.J.; Middleton, J.P. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J. Am. Soc. Nephrol. 2019, 30, 1096–1108. [Google Scholar] [CrossRef]
- Qunibi, W.; Winkelmayer, W.C.; Solomon, R.; Moustafa, M.; Kessler, P.; Ho, C.; Greenberg, J.; Diaz-Buxo, J.A. A Randomized, Double-Blind, Placebo-Controlled Trial of Calcium Acetate on Serum Phosphorus Concentrations in Patients with Advanced Non-Dialysis-Dependent Chronic Kidney Disease. BMC Nephrol. 2011, 12, 9. [Google Scholar] [CrossRef] [PubMed]
- Young, D.O.; Cheng, S.C.; Delmez, J.A.; Coyne, D.W. The Effect of Oral Niacinamide on Plasma Phosphorus Levels in Peritoneal Dialysis Patients. Perit. Dial. Int. 2009, 29, 562–567. [Google Scholar] [PubMed]
- Shahbazian, H.; Shahbazian, H.; Zafar Mohtashami, A.; Zafar Mohtashami, A.; Ghorbani, A.; Ghorbani, A.; Abbaspour, M.R.; Abbaspour, M.R.; Belladi Musavi, S.S.; Musavi, B. Oral Nicotinamide Reduces Serum Phosphorus, Increases HDL, and Induces Thrombocytopenia in Hemodialysis Patients: A Double-Blind Randomized Clinical Trial. Nefrología (Engl. Ed.) 2011, 31, 58–65. [Google Scholar]
- Vasantha, J.; Soundararajan, P.; Vanitharani, N.; Kannan, G.; Thennarasu, P.; Neenu, G.; Reddy, C.U. Safety and Efficacy of Nicotinamide in the Management of Hyperphosphatemia in Patients on Hemodialysis. Indian J. Nephrol. 2011, 21, 245. [Google Scholar] [CrossRef]
- Takahashi, Y.; Tanaka, A.; Nakamura, T.; Fukuwatari, T.; Shibata, K.; Shimada, N.; Ebihara, I.; Koide, H. Nicotinamide Suppresses Hyperphosphatemia in Hemodialysis Patients. Kidney Int. 2004, 65, 1099–1104. [Google Scholar] [CrossRef]
- Cheng, S.C.; Young, D.O.; Huang, Y.; Delmez, J.A.; Coyne, D.W. A Randomized, Double-Blind, Placebo-Controlled Trial of Niacinamide for Reduction of Phosphorus in Hemodialysis Patients. Clin. J. Am. Soc. Nephrol. 2008, 3, 1131–1138. [Google Scholar] [CrossRef] [Green Version]
- Sakaguchi, Y.; Hamano, T.; Obi, Y.; Monden, C.; Oka, T.; Yamaguchi, S.; Matsui, I.; Hashimoto, N.; Matsumoto, A.; Shimada, K. A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD. J. Am. Soc. Nephrol. 2019, 30, 1073–1085. [Google Scholar] [CrossRef]
- Bressendorff, I.; Hansen, D.; Schou, M.; Pasch, A.; Brandi, L. The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney Disease A Randomized, Controlled Clinical Trial. Clin. J. Am. Soc. Nephrol. 2018, 13, 1373–1380. [Google Scholar] [CrossRef]
- Larsson, T.E.; Kameoka, C.; Nakajo, I.; Taniuchi, Y.; Yoshida, S.; Akizawa, T.; Smulders, R.A. NPT-IIb Inhibition does Not Improve Hyperphosphatemia in CKD. Kidney Int. Rep. 2018, 3, 73–80. [Google Scholar] [CrossRef]
- Katai, K.; Tanaka, H.; Tatsumi, S.; Fukunaga, Y.; Genjida, K.; Morita, K.; Kuboyama, N.; Suzuki, T.; Akiba, T.; Miyamoto, K. Nicotinamide Inhibits Sodium-Dependent Phosphate Cotransport Activity in Rat Small Intestine. Nephrol. Dial. Transplant. 1999, 14, 1195–1201. [Google Scholar] [CrossRef]
- Eto, N.; Miyata, Y.; Ohno, H.; Yamashita, T. Nicotinamide Prevents the Development of Hyperphosphataemia by Suppressing Intestinal Sodium-Dependent Phosphate Transporter in Rats with Adenine-Induced Renal Failure. Nephrol. Dial. Transplant. 2005, 20, 1378–1384. [Google Scholar] [CrossRef] [PubMed]
- Rao, M.; Steffes, M.; Bostom, A.; Ix, J.H. Effect of Niacin on FGF23 Concentration in Chronic Kidney Disease. Am. J. Nephrol. 2014, 39, 484–490. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Louvet, L.; Büchel, J.; Steppan, S.; Passlick-Deetjen, J.; Massy, Z.A. Magnesium Prevents Phosphate-Induced Calcification in Human Aortic Vascular Smooth Muscle Cells. Nephrol. Dial. Transplant. 2012, 28, 869–878. [Google Scholar] [CrossRef]
- De Oca, A.M.; Guerrero, F.; Martinez-Moreno, J.M.; Madueno, J.A.; Herencia, C.; Peralta, A.; Almaden, Y.; Lopez, I.; Aguilera-Tejero, E.; Gundlach, K. Magnesium Inhibits Wnt/Β-Catenin Activity and Reverses the Osteogenic Transformation of Vascular Smooth Muscle Cells. PLoS ONE 2014, 9, e89525. [Google Scholar]
- ter Braake, A.D.; Tinnemans, P.T.; Shanahan, C.M.; Hoenderop, J.G.; de Baaij, J.H. Magnesium Prevents Vascular Calcification in Vitro by Inhibition of Hydroxyapatite Crystal Formation. Sci. Rep. 2018, 8, 2069. [Google Scholar] [CrossRef]
- Sakaguchi, Y.; Fujii, N.; Shoji, T.; Hayashi, T.; Rakugi, H.; Iseki, K.; Tsubakihara, Y.; Isaka, Y.; Committee of Renal Data Registry of the Japanese Society for Dialysis Therapy. Magnesium Modifies the Cardiovascular Mortality Risk Associated with Hyperphosphatemia in Patients Undergoing Hemodialysis: A Cohort Study. PLoS ONE 2014, 9, e116273. [Google Scholar] [CrossRef]
- Sakaguchi, Y.; Iwatani, H.; Hamano, T.; Tomida, K.; Kawabata, H.; Kusunoki, Y.; Shimomura, A.; Matsui, I.; Hayashi, T.; Tsubakihara, Y.; et al. Magnesium Modifies the Association between Serum Phosphate and the Risk of Progression to End-Stage Kidney Disease in Patients with Non-Diabetic Chronic Kidney Disease. Kidney Int. 2015, 88, 833–842. [Google Scholar] [CrossRef]
- Sakaguchi, Y.; Hamano, T.; Matsui, I.; Oka, T.; Yamaguchi, S.; Kubota, K.; Shimada, K.; Matsumoto, A.; Hashimoto, N.; Isaka, Y. Low Magnesium Diet Aggravates Phosphate-Induced Kidney Injury. Nephrol. Dial. Transplant. 2018, 34, 1310–1319. [Google Scholar] [CrossRef]
- Yao, Z.; Xu, Y.; Ma, W.; Sun, X.; Jia, S.; Zheng, Y.; Liu, X.; Fan, Y.; Wang, C. Magnesium Citrate Protects Against Vascular Calcification in an Adenine-Induced Chronic Renal Failure Rat Model. J. Cardiovasc. Pharm. 2018, 72, 270–276. [Google Scholar] [CrossRef]
- Kaesler, N.; Goettsch, C.; Weis, D.; Schurgers, L.; Hellmann, B.; Floege, J.; Kramann, R. Magnesium but Not Nicotinamide Prevents Vascular Calcification in Experimental Uraemia. Nephrol. Dial. Transplant. 2019, 1–9. [Google Scholar] [CrossRef]
- Schiavi, S.C.; Tang, W.; Bracken, C.; O’Brien, S.P.; Song, W.; Boulanger, J.; Ryan, S.; Phillips, L.; Liu, S.; Arbeeny, C. Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD. J. Am. Soc. Nephrol. 2012, 23, 1691–1700. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thomas, L.; Xue, J.; Murali, S.K.; Fenton, R.A.; Rieg, J.A.D.; Rieg, T. Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice with Normal and Reduced Kidney Function. J. Am. Soc. Nephrol. 2019, 30, 2128–2139. [Google Scholar] [CrossRef] [PubMed]
- Dussold, C.; Gerber, C.; White, S.; Wang, X.; Qi, L.; Francis, C.; Capella, M.; Courbon, G.; Wang, J.; Li, C. DMP1 Prevents Osteocyte Alterations, FGF23 Elevation and Left Ventricular Hypertrophy in Mice with Chronic Kidney Disease. Bone Res. 2019, 7, 12. [Google Scholar] [CrossRef] [PubMed]
Class of drug | Drug | Advantages | Disadvantages |
---|---|---|---|
Non-calcium phosphate binders | Sevelamer | Lower intact FGF23 and urinary Pi secretion, hypolipidemic [150,151,152] | GI side effects, high pill burden, unchanged serum Pi [150,151,152] |
Lanthanum carbonate | Good GI tolerance, lower C-term FGF23 [154] | Unchanged serum Pi and intact FGF23 [151,155,160], low solubility: tissue accumulation might cause long-term toxicity | |
Ferric citrate | Lower serum Pi and intact FGF23, increase hemoglobin and ferritin [153,157,158] | Mild GI side effects [153,157,158] | |
Calcium-based phosphate binders | Calcium carbonate/acetate | Controlled [150,151] or lower [161] serum Pi | Hypercalcemia, VC, unchanged or increased intact FGF23 [150,151] |
Nicotinamide | Lower serum Pi and intact FGF23 in dialysis patients [162,163,164] | Unchanged serum Pi and intact FGF23 in non-dialysis patients [160], mild GI side effects, at high doses hepatotoxic/thrombocytopenia [162,163,164,165,166] | |
Magnesium supplements | Oral magnesium oxide | Slower progression of VC [167] | Unchanged serum Pi, FGF23 not measured, Mild GI side effects [167] |
Higher dialysate magnesium | Increased conversion time from primary CPP to secondary CPP (T50 test, lower serum Pi [168] | Unchanged serum Pi, FGF23 not measured [168] | |
Pi-transporter inhibitor | NaPi-2b inhibitor | Not effective in reducing serum Pi [169] |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Vogt, I.; Haffner, D.; Leifheit-Nestler, M. FGF23 and Phosphate–Cardiovascular Toxins in CKD. Toxins 2019, 11, 647. https://doi.org/10.3390/toxins11110647
Vogt I, Haffner D, Leifheit-Nestler M. FGF23 and Phosphate–Cardiovascular Toxins in CKD. Toxins. 2019; 11(11):647. https://doi.org/10.3390/toxins11110647
Chicago/Turabian StyleVogt, Isabel, Dieter Haffner, and Maren Leifheit-Nestler. 2019. "FGF23 and Phosphate–Cardiovascular Toxins in CKD" Toxins 11, no. 11: 647. https://doi.org/10.3390/toxins11110647