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International Journal of Hypertension
Volume 2014, Article ID 381082, 9 pages
http://dx.doi.org/10.1155/2014/381082
Review Article

Cardiovascular Risk Factors and Chronic Kidney Disease—FGF23: A Key Molecule in the Cardiovascular Disease

1Department of Internal Medicine, Odaira-Memorial Tokyo Hitachi Hospital, 3-5-7 Yushima, Bunkyo-ku, Tokyo, Japan
2Department of Clinical Laboratory, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan

Received 30 October 2013; Accepted 23 December 2013; Published 12 January 2014

Academic Editor: Kazushi Tsuda

Copyright © 2014 Rika Jimbo and Tatsuo Shimosawa. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. S. Go, G. M. Chertow, D. Fan, C. E. McCulloch, and C.-Y. Hsu, “Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization,” The New England Journal of Medicine, vol. 351, no. 13, pp. 1296–1370, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Ninomiya, Y. Kiyohara, M. Kubo et al., “Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama study,” Kidney International, vol. 68, no. 1, pp. 228–236, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. R. N. Foley, P. S. Parfrey, and M. J. Sarnak, “Clinical epidemiology of cardiovascular disease in chronic renal disease,” American Journal of Kidney Diseases, vol. 32, no. 5, supplement 3, pp. S112–S119, 1998. View at Google Scholar · View at Scopus
  4. C. A. Herzog, J. Z. Ma, and A. J. Collins, “Poor long-term survival after acute myocardial infarction among patients on long-term dialysis,” The New England Journal of Medicine, vol. 339, no. 12, pp. 799–805, 1998. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Wanner, V. Krane, W. März et al., “Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis,” The New England Journal of Medicine, vol. 353, no. 3, pp. 238–248, 2005. View at Publisher · View at Google Scholar
  6. S. Moe, T. Drüeke, J. Cunningham et al., “Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO),” Kidney International, vol. 69, no. 11, pp. 1945–1953, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. S. M. Moe, T. B. Drüeke, G. A. Block et al., “KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD),” Kidney International, vol. 113, pp. S1–S130, 2009. View at Google Scholar
  8. R. Bhuriya, S. Li, S.-C. Chen, P. A. McCullough, and G. L. Bakris, “Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD stages 3 and 4: an analysis from the Kidney Early Evaluation Program (KEEP),” American Journal of Kidney Diseases, vol. 53, no. 4, supplement 4, pp. S3–S10, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. N. Kimata, J. M. Albert, T. Akiba et al., “Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS),” Hemodialysis International, vol. 11, no. 3, pp. 340–348, 2007. View at Google Scholar
  10. M. Wolf and R. Thadhani, “Vitamin D in patients with renal failure: a summary of observational mortality studies and steps moving forward,” Journal of Steroid Biochemistry and Molecular Biology, vol. 103, no. 3–5, pp. 487–490, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. P. Evenepoel, B. Meijers, L. Viaene et al., “Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism,” Clinical Journal of the American Society of Nephrology, vol. 5, no. 7, pp. 1268–1276, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Isakova, P. Wahl, G. S. Vargas et al., “Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease,” Kidney International, vol. 79, no. 12, pp. 1370–1378, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. ADHR Consortium, “Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23,” Nature Genetics, vol. 26, no. 3, pp. 345–348, 2000. View at Publisher · View at Google Scholar
  14. T. Shimada, S. Mizutani, T. Muto et al., “Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 11, pp. 6500–6505, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Larsson, R. Marsell, E. Schipani et al., “Transgenic mice expressing fibroblast growth factor 23 under the control of the α1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis,” Endocrinology, vol. 145, no. 7, pp. 3087–3094, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Gattineni, C. Bates, K. Twombley et al., “FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1,” American Journal of Physiology: Renal Physiology, vol. 297, no. 2, pp. F282–F291, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. L. Dailey, D. Ambrosetti, A. Mansukhani, and C. Basilico, “Mechanisms underlying differential responses to FGF signaling,” Cytokine and Growth Factor Reviews, vol. 16, no. 2, pp. 233–247, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. V. P. Eswarakumar, I. Lax, and J. Schlessinger, “Cellular signaling by fibroblast growth factor receptors,” Cytokine and Growth Factor Reviews, vol. 16, no. 2, pp. 139–149, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. X. Yu, O. A. Ibrahimi, R. Goetz et al., “Analysis of the biochemical mechanisms for the endocrine actions of fibroblast growth factor-23,” Endocrinology, vol. 146, no. 11, pp. 4647–4656, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. H. Li, A. Martin, V. David, and L. D. Quarles, “Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype,” American Journal of Physiology: Endocrinology and Metabolism, vol. 300, no. 3, pp. E508–E517, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. I. Z. Ben-Dov, H. Galitzer, V. Lavi-Moshayoff et al., “The parathyroid is a target organ for FGF23 in rats,” Journal of Clinical Investigation, vol. 117, no. 12, pp. 4003–4008, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Yamazaki, K. Ozono, T. Okada et al., “Both FGF23 and extracellular phosphate activate Raf/MEK/ERK pathway via FGF receptors in HEK293 cells,” Journal of Cellular Biochemistry, vol. 111, no. 5, pp. 1210–1221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. I. Urakawa, Y. Yamazaki, T. Shimada et al., “Klotho converts canonical FGF receptor into a specific receptor for FGF23,” Nature, vol. 444, no. 7120, pp. 770–774, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. M. C. Hu, M. Shi, J. Zhang et al., “Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule,” FASEB Journal, vol. 24, no. 9, pp. 3438–3450, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Kuro-O, “Phosphate and Klotho,” Kidney International, no. 121, pp. S20–S23, 2011. View at Google Scholar · View at Scopus
  26. T. Shimada, I. Urakawa, Y. Yamazaki et al., “FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa,” Biochemical and Biophysical Research Communications, vol. 314, no. 2, pp. 409–414, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. X. Yan, H. Yokote, X. Jing et al., “Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cells,” Genes to Cells, vol. 10, no. 5, pp. 489–502, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. T. Shimada, H. Hasegawa, Y. Yamazaki et al., “FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis,” Journal of Bone and Mineral Research, vol. 19, no. 3, pp. 429–435, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. H. Hasegawa, N. Nagano, I. Urakawa et al., “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 International, vol. 78, no. 10, pp. 975–980, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Liu, W. Tang, J. Zhou et al., “Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D,” Journal of the American Society of Nephrology, vol. 17, no. 5, pp. 1305–1315, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. R. Masuyama, I. Stockmans, S. Torrekens et al., “Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts,” Journal of Clinical Investigation, vol. 116, no. 12, pp. 3150–3159, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. T. Shimada, Y. Yamazaki, M. Takahashi et al., “Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism,” American Journal of Physiology: Renal Physiology, vol. 289, no. 5, pp. F1088–F1095, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Nishi, T. Nii-Kono, S. Nakanishi et al., “Intravenous calcitriol therapy increases serum concentrations of fibroblast growth factor-23 in dialysis patients with secondary hyperparathyroidism,” Nephron, vol. 101, no. 2, pp. c94–c99, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. D. Hansen, K. Rasmussen, S. M. Pedersen, L. M. Rasmussen, and L. Brandi, “Changes in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol,” Nephrology Dialysis Transplantation, vol. 27, no. 6, pp. 2263–2269, 2012. View at Publisher · View at Google Scholar
  35. H. Komaba and M. Fukagawa, “FGF23-parathyroid interaction: implications in chronic kidney disease,” Kidney International, vol. 77, no. 4, pp. 292–298, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Krajisnik, P. Björklund, R. Marsell et al., “Fibroblast growth factor-23 regulates parathyroid hormone and 1α-hydroxylase expression in cultured bovine parathyroid cells,” Journal of Endocrinology, vol. 195, no. 1, pp. 125–131, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Hofman-Bang, G. Martuseviciene, M. A. Santini, K. Olgaard, and E. Lewin, “Increased parathyroid expression of klotho in uremic rats,” Kidney International, vol. 78, no. 11, pp. 1119–1127, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Canalejo, A. Canalejo, J. M. Martinez-Moreno et al., “FGF23 fails to inhibit uremic parathyroid glands,” Journal of the American Society of Nephrology, vol. 21, no. 7, pp. 1125–1135, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. F. Saji, T. Shigematsu, T. Sakaguchi et al., “Fibroblast growth factor 23 production in bone is directly regulated by 1α,25-dihydroxyvitamin D, but not PTH,” American Journal of Physiology: Renal Physiology, vol. 299, no. 5, pp. F1212–F1217, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. I. López, M. E. Rodríguez-Ortiz, Y. Almadén et al., “Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo,” Kidney International, vol. 80, no. 5, pp. 475–482, 2011. View at Publisher · View at Google Scholar
  41. Y. Rhee, N. Bivi, E. Farrow et al., “Parathyroid hormone receptor signaling in osteocytes increases the expression of fibroblast growth factor-23 in vitro and in vivo,” Bone, vol. 49, no. 4, pp. 636–643, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. S.-A. M. Burnett-Bowie, M. P. Henao, M. E. Dere, H. Lee, and B. Z. Leder, “Effects of hPTH(1-34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men,” Journal of Bone and Mineral Research, vol. 24, no. 10, pp. 1681–1685, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. O. M. Gutiérrez, K. T. Smith, A. Barchi-Chung, N. M. Patel, T. Isakova, and M. Wolf, “(1-34) parathyroid hormone infusion acutely lowers fibroblast growth factor 23 concentrations in adult volunteers,” Clinical Journal of the American Society of Nephrology, vol. 7, no. 1, pp. 139–145, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Wesseling-Perry, G. C. Harkins, H.-J. Wang et al., “The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84),” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 6, pp. 2772–2780, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. O. M. Gutiérrez, M. Mannstadt, T. Isakova et al., “Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis,” The New England Journal of Medicine, vol. 359, no. 6, pp. 584–592, 2008. View at Publisher · View at Google Scholar
  46. S. Seiler, B. Reichart, D. Roth, E. Seibert, D. Fliser, and G. H. Heine, “FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment,” Nephrology Dialysis Transplantation, vol. 25, no. 12, pp. 3983–3989, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Kendrick, A. K. Cheung, J. S. Kaufman et al., “FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis,” Journal of the American Society of Nephrology, vol. 22, no. 10, pp. 1913–1922, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. N. Koh, T. Fujimori, S. Nishiguchi et al., “Severely reduced production of klotho in human chronic renal failure kidney,” Biochemical and Biophysical Research Communications, vol. 280, no. 4, pp. 1015–1020, 2001. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Jean, J.-C. Terrat, T. Vanel et al., “High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients,” Nephrology Dialysis Transplantation, vol. 24, no. 9, pp. 2792–2796, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Olauson, A. R. Qureshi, T. Miyamoto et al., “Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship?” Nephrology Dialysis Transplantation, vol. 25, no. 9, pp. 3033–3038, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Isakova, H. Xie, W. Yang et al., “Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease,” Journal of the American Medical Association, vol. 305, no. 23, pp. 2432–2439, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Nakano, T. Hamano, N. Fujii et al., “Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis,” Bone, vol. 50, no. 6, pp. 1266–1274, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. H. J. Hsu and M.-S. Wu, “Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients,” American Journal of the Medical Sciences, vol. 337, no. 2, pp. 116–122, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. O. M. Gutiérrez, J. L. Januzzi, T. Isakova et al., “Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease,” Circulation, vol. 119, no. 19, pp. 2545–2552, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Kirkpantur, M. Balci, O. A. Gurbuz et al., “Serum fibroblast growth factor-23 (FGF-23) levels are independently associated with left ventricular mass and myocardial performance index in maintenance haemodialysis patients,” Nephrology Dialysis Transplantation, vol. 26, no. 4, pp. 1346–1354, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. C. Faul, A. P. Amaral, B. Oskouei et al., “FGF23 induces left ventricular hypertrophy,” Journal of Clinical Investigation, vol. 121, no. 11, pp. 4393–4408, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. V. Shalhoub, E. M. Shatzen, S. C. Ward et al., “FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality,” Journal of Clinical Investigation, vol. 122, no. 7, pp. 2543–2553, 2012. View at Publisher · View at Google Scholar
  58. G. M. London, A. P. Guérin, S. J. Marchais, F. Métivier, B. Pannier, and H. Adda, “Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality,” Nephrology Dialysis Transplantation, vol. 18, no. 9, pp. 1731–1740, 2003. View at Publisher · View at Google Scholar · View at Scopus
  59. C. M. Shanahan, M. H. Crouthamel, A. Kapustin, and C. M. Giachelli, “Arterial calcification in chronic kidney disease: key roles for calcium and phosphate,” Circulation Research, vol. 109, no. 6, pp. 697–711, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. K. Hruska, S. Mathew, R. Lund, Y. Fang, and T. Sugatani, “Cardiovascular risk factors in chronic kidney disease: does phosphate qualify?” Kidney international, vol. 79, supplement 121, pp. S9–S13, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Jono, M. D. McKee, C. E. Murry et al., “Phosphate regulation of vascular smooth muscle cell calcification,” Circulation Research, vol. 87, no. 7, pp. E10–E17, 2000. View at Google Scholar · View at Scopus
  62. X. Li, H.-Y. Yang, and C. M. Giachelli, “Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification,” Circulation Research, vol. 98, no. 7, pp. 905–912, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Y. Speer, H.-Y. Yang, T. Brabb et al., “Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries,” Circulation Research, vol. 104, no. 6, pp. 733–741, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. W. G. Goodman, J. Goldin, B. D. Kuizon et al., “Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis,” The New England Journal of Medicine, vol. 342, no. 20, pp. 1478–1483, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. K. L. Adeney, D. S. Siscovick, J. H. Ix et al., “Association of serum phosphate with vascular and valvular calcification in moderate CKD,” Journal of the American Society of Nephrology, vol. 20, no. 2, pp. 381–387, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. J. H. Ix, I. H. de Boer, C. A. Peralta et al., “Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA,” Clinical Journal of the American Society of Nephrology, vol. 4, no. 3, pp. 609–615, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. R. Villa-Bellosta, Y. E. Bogaert, M. Levi, and V. Sorribas, “Characterization of phosphate transport in rat vascular smooth muscle cells: implications for vascular calcification,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 5, pp. 1030–1036, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Taylor, M. Butcher, M. Zeadin, A. Politano, and S. G. Shaughnessy, “Oxidized low-density lipoprotein promotes osteoblast differentiation in primary cultures of vascular smooth muscle cells by up-regulating Osterix expression in an Msx2-dependent manner,” Journal of Cellular Biochemistry, vol. 112, no. 2, pp. 581–588, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Mitani, N. Ishizaka, T. Aizawa et al., “In vivo Klotho gene transfer ameliorates angiotensin II-induced renal damage,” Hypertension, vol. 39, no. 4, pp. 838–843, 2002. View at Publisher · View at Google Scholar · View at Scopus
  70. R. Nakano-Kurimoto, K. Ikeda, M. Uraoka et al., “Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 297, no. 5, pp. H1673–H1684, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Donate-Correa, C. Mora-Fernández, and R. Martínez-Sanz, “Expression of FGF23/KLOTHO system in human vascular tissue,” International Journal of Cardiology, vol. 165, no. 1, pp. 179–183, 2013. View at Publisher · View at Google Scholar
  72. K. Lim, T. S. Lu, G. Molostvov et al., “Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23,” Circulation, vol. 125, no. 18, pp. 2243–2255, 2012. View at Publisher · View at Google Scholar
  73. J. J. Scialla, W. L. Lau, M. P. Reilly et al., “Fibroblast growth factor 23 is not associated with and does not induce arterial calcification,” Kidney International, vol. 83, no. 6, pp. 1159–1168, 2013. View at Publisher · View at Google Scholar
  74. K. Lindberg, H. Olauson, R. Amin et al., “Arterial klotho expression and FGF23 effects on vascular calcification and function,” PLoS ONE, vol. 8, no. 4, Article ID e60658, 2013. View at Publisher · View at Google Scholar
  75. Y. Fang, C. Ginsberg, T. Sugatani, M. C. Monier-Faugere, H. Malluche, and K. A. Hruska, “Early chronic kidney disease-mineral bone disorder stimulates vascular calcification,” Kidney International, 2013. View at Publisher · View at Google Scholar
  76. R. Jimbo, F. Kawakami-Mori, S. Mu et al., “Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification in the absence of Klotho deficiency,” Kidney International, 2013. View at Publisher · View at Google Scholar
  77. M. Nakayama, Y. Kaizu, M. Nagata et al., “Fibroblast growth factor 23 is associated with carotid artery calcification in chronic kidney disease patients not undergoing dialysis: a cross-sectional study,” BMC Nephrology, vol. 14, article 22, 2013. View at Publisher · View at Google Scholar
  78. M. Balci, A. Kirkpantur, M. Gulbay, and O. A. Gurbuz, “Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients,” Hemodialysis International, vol. 14, no. 4, pp. 425–432, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. M. M. Nasrallah, A. R. El-Shehaby, M. M. Salem, N. A. Osman, E. El Sheikh, and U. A. Sharaf El Din, “Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients,” Nephrology Dialysis Transplantation, vol. 25, no. 8, pp. 2679–2685, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. S.-A. M. Burnett, S. C. Gunawardene, F. R. Bringhurst, H. Jüppner, H. Lee, and J. S. Finkelstein, “Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women,” Journal of Bone and Mineral Research, vol. 21, no. 8, pp. 1187–1196, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. S. L. Ferrari, J.-P. Bonjour, and R. Rizzoli, “Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 3, pp. 1519–1524, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Isakova, O. M. Gutirrez, K. Smith et al., “Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease,” Nephrology Dialysis Transplantation, vol. 26, no. 2, pp. 584–591, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. T. Isakova, A. Barchi-Chung, G. Enfield et al., “Effects of dietary phosphate restriction and phosphate binders on FGF23 levels in CKD,” Clinical Journal of the American Society of Nephrology, vol. 8, no. 6, pp. 1009–1018, 2013. View at Publisher · View at Google Scholar
  84. A. L. E. Cancela, R. B. Oliveira, F. G. Graciolli et al., “Fibroblast growth factor 23 in hemodialysis patients: effects of phosphate binder, calcitriol and calcium concentration in the dialysate,” Nephron, vol. 117, no. 1, pp. c74–c82, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. F. Koiwa, J. J. Kazama, A. Tokumoto et al., “Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients,” Therapeutic Apheresis and Dialysis, vol. 9, no. 4, pp. 336–339, 2005. View at Google Scholar · View at Scopus
  86. R. B. Oliveira, A. L. E. Cancela, F. G. Graciolli et al., “Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy?” Clinical Journal of the American Society of Nephrology, vol. 5, no. 2, pp. 286–291, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. C. D. Chue, J. N. Townend, W. E. Moody et al., “Cardiovascular effects of sevelamer in stage 3 CKD,” Journal of the American Society of Nephrology, vol. 24, no. 5, pp. 842–852, 2013. View at Publisher · View at Google Scholar
  88. E. Gonzalez-Parra, M. L. Gonzalez-Casaus, A. Galán et al., “Lanthanum carbonate reduces FGF23 in chronic kidney disease stage 3 patients,” Nephrology Dialysis Transplantation, vol. 26, no. 8, pp. 2567–2571, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. S. Soriano, R. Ojeda, M. Rodríguez et al., “The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients,” Clinical Nephrology, vol. 80, no. 1, pp. 17–22, 2013. View at Publisher · View at Google Scholar
  90. M. Koizumi, H. Komaba, S. Nakanishi, A. Fujimori, and M. Fukagawa, “Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism,” Nephrology Dialysis Transplantation, vol. 27, no. 2, pp. 784–790, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. J. B. Wetmore, S. Liu, R. Krebill, R. Menard, and L. D. Quarles, “Effects of cinacalcet and concurrent low-dose vitamin D on FGF23 levels in ESRD,” Clinical Journal of the American Society of Nephrology, vol. 5, no. 1, pp. 110–116, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. H. J. Kim, H. Kim, N. Shin et al., “Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study,” BMC Nephrology, vol. 14, article 112, 2013. View at Publisher · View at Google Scholar
  93. J. L. Finch, M. Tokumoto, H. Nakamura et al., “Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease,” American Journal of Physiology: Renal Physiology, vol. 298, no. 6, pp. F1315–F1322, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. K. Wesseling-Perry, R. C. Pereira, S. Sahney et al., “Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism,” Kidney International, vol. 79, no. 1, pp. 112–119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Teng, M. Wolf, M. N. Ofsthun et al., “Activated injectable vitamin D and hemodialysis survival: a historical cohort study,” Journal of the American Society of Nephrology, vol. 16, no. 4, pp. 1115–1125, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Naves-Díaz, D. Alvarez-Hernández, J. Passlick-Deetjen et al., “Oral active vitamin D is associated with improved survival in hemodialysis patients,” Kidney International, vol. 74, no. 8, pp. 1070–1078, 2008. View at Publisher · View at Google Scholar
  97. H. Zebger-Gong, D. Müller, M. Diercke et al., “1,25-dihydroxyvitamin D3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix,” Journal of Hypertension, vol. 29, no. 2, pp. 339–348, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. T. B. Drüeke, “Role of vitamin D in vascular calcification: bad guy or good guy?” Nephrology Dialysis Transplantation, vol. 27, no. 5, pp. 1704–1707, 2012. View at Publisher · View at Google Scholar
  99. Y. Aoshima, M. Mizobuchi, H. Ogata et al., “Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-α,” Nephrology Dialysis Transplantation, vol. 27, no. 5, pp. 1800–1806.
  100. N. Bodyak, J. C. Ayus, S. Achinger et al., “Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 43, pp. 16810–16815, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. R. Thadhani, E. Appelbaum, Y. Pritchett et al., “Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial,” Journal of the American Medical Association, vol. 307, no. 7, pp. 674–684, 2012. View at Publisher · View at Google Scholar · View at Scopus