FGF-23: The rise of a novel cardiovascular risk marker in CKD

Nephrology Dialysis Transplantation

Volumn 27, Issue 8, 2012, Pages 3072-3081

  Heine, Gunnar H ^a   Seiler, Sarah ^a   Fliser, Danilo ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

calcium; cardiovascular disease; CKD; FGF 23; phosphate

Indexed keywords

CALCIUM; CYTOKINE RECEPTOR ANTAGONIST; FIBROBLAST GROWTH FACTOR 23; FIBROBLAST GROWTH FACTOR 23 BLOCKING AGENT; FIBROBLAST GROWTH FACTOR RECEPTOR ANTAGONIST; PHOSPHATE; PHOSPHATE BINDING AGENT; UNCLASSIFIED DRUG;

ARTICLE; CALCIUM METABOLISM; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC KIDNEY DISEASE; DISEASE ASSOCIATION; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE INJURY; HEART PROTECTION; HEMODIALYSIS PATIENT; HUMAN; HYPERPHOSPHATEMIA; HYPERPHOSPHATONINISM; KIDNEY FAILURE; LABORATORY TEST; METABOLIC DISORDER; NONHUMAN; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PHOSPHATE BALANCE; PHOSPHATE BLOOD LEVEL; PHOSPHATE METABOLISM; PHOSPHATURIA; PRIORITY JOURNAL; PROGNOSIS; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RENAL REPLACEMENT THERAPY;

BIOLOGICAL MARKERS; CALCIUM; CARDIOVASCULAR DISEASES; DISEASE PROGRESSION; FIBROBLAST GROWTH FACTORS; HUMANS; MODELS, BIOLOGICAL; PHOSPHATES; PHOSPHORUS METABOLISM DISORDERS; PROGNOSIS; RENAL INSUFFICIENCY, CHRONIC; RISK FACTORS;

EID: 84864579854     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfs259     Document Type: Article

References (88)

1. de Jager DJ, Grootendorst DC, Jager KJ et al. Cardiovascular and noncardiovascular mortality among patients starting dialysis. J Am Med Assoc 2009; 302: 1782-1789.
2. Matsushita K, van der Velde M, Astor BC et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010; 375: 2073-2081.
3. Herzog CA, Asinger RW, Berger AK et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011; 80: 572-586.
4. Weiner DE, Tighiouart H, Elsayed EF et al. The Framingham predictive instrument in chronic kidney disease. J Am Coll Cardiol 2007; 50: 217-224.
5. Zannad F, Kessler M, Lehert P et al. Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int 2006; 70: 1318-1324.
6. Fellstrom BC, Jardine AG, Schmieder RE et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360: 1395-1407.
7. Wanner C, Krane V, Marz Wet al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238-248.
8. Besarab A, Bolton WK, Browne JK et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584-590.
9. Heinz J, Kropf S, Domrose U et al. B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial. Circulation 2010; 121: 1432-1438.
10. Jamison RL, Hartigan P, Kaufman JS et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. J Am Med Assoc 2007; 298: 1163-1170.
11. Wrone EM, Hornberger JM, Zehnder JL et al. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol 2004; 15: 420-426.
12. Cooper BA, Branley P, Bulfone L et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med 2010; 363: 609-619.
13. Eknoyan G, Beck GJ, Cheung AK et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347: 2010-2019.
14. Ravani P, Malberti F, Tripepi G et al. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int 2009; 75: 88-95.
15. Tentori F, Blayney MJ, Albert JM et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008; 52: 519-530.
16. Wald R, Sarnak MJ, Tighiouart H et al. Disordered mineral metabolism in hemodialysis patients: an analysis of cumulative effects in the Hemodialysis (HEMO) Study. Am J Kidney Dis 2008; 52: 531-540.
17. Wolf M, Shah A, Gutierrez O et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 2007; 72: 1004-1013.
18. Isakova T, Gutierrez OM, Chang Y et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 2009; 20: 388-396.
19. Block GA, Spiegel DM, Ehrlich J et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005; 68: 1815-1824.
20. de Zeeuw D, Agarwal R, Amdahl M et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 2010; 376: 1543-1551.
21. Raggi P, Chertow GM, Torres PU et al. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant 2011; 26: 1327-1339.
22. Fukumoto S. Physiological regulation and disorders of phosphate metabolism-pivotal role of fibroblast growth factor.23. Intern Med 2008; 47: 337-343.
23. Jagtap VS, Sarathi V, Lila AR et al. Hypophosphatemic rickets. Indian J Endocrinol Metab 2012; 16: 177-182.
24. Quarles LD. Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Exp Cell Res 2012; 318: 1040-1048.
25. Wolf M. Fibroblast growth factor 23 and the future of phosphorus management. Curr Opin Nephrol Hypertens 2009; 18: 463-468.
26. Riminucci M, Collins MT, Fedarko NS et al. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 2003; 112: 683-692.
27. Goetz R, Beenken A, Ibrahimi OA et al. Molecular insights into the Klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol 2007; 27: 3417-3428.
28. Yamashita T. Structural and biochemical properties of fibroblast growth factor. 23. Ther Apher Dial 2005; 9: 313-318.
29. Tohyama O, Imura A, Iwano A et al. Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides. J Biol Chem 2004; 279: 9777-9784.
30. Baum M, Schiavi S, Dwarakanath V et al. Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules. Kidney Int 2005; 68: 1148-1153.
31. Miyamoto K, Ito M, Kuwahata M et al. Inhibition of intestinal sodium-dependent inorganic phosphate transport by fibroblast growth factor. 23. Ther Apher Dial 2005; 9: 331-335.
32. Shimada T, Hasegawa H, Yamazaki Y et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004; 19: 429-435.
33. Liu S, Tang W, Zhou J et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol 2006; 17: 1305-1315.
34. Krajisnik T, Bjorklund P, Marsell R et al. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 2007; 195: 125-131.
35. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest 2007; 117: 4003-4008.
36. Hofman-Bang J, Martuseviciene G, Santini MA et al. Increased parathyroid expression of Klotho in uremic rats. Kidney Int 2010; 78: 1119-1127.
37. Lopez I, Rodriguez-Ortiz ME, Almaden Y et al. Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo. Kidney Int 2011; 80: 475-482.
38. Saji F, Shigematsu T, Sakaguchi T et al. Fibroblast growth factor 23 production in bone is directly regulated by 1{alpha},25-dihydroxyvitamin D, but not PTH. Am J Physiol Renal Physiol 2010; 299: F1212-F1217.
39. Samadfam R, Richard C, Nguyen-Yamamoto L et al. Bone formation regulates circulating concentrations of fibroblast growth factor. 23. Endocrinology 2009; 150: 4835-4845.
40. Burnett-Bowie SM, Henao MP, Dere ME et al. Effects of hPTH(1- 34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men. J Bone Miner Res 2009; 24: 1681-1685.
41. Gutierrez OM, Smith KT, Barchi-Chung A et al. (1-34) Parathyroid hormone infusion acutely lowers fibroblast growth factor 23 concentrations in adult volunteers. Clin J Am Soc Nephrol 2012; 7: 139-145.
42. Wesseling-Perry K, Harkins GC, Wang HJ 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). J Clin Endocrinol Metab 2010; 95: 2772-2780.
43. Larsson T, Nisbeth U, Ljunggren O et al. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 2003; 64: 2272-2279.
44. Gutierrez O, Isakova T, Rhee E et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005; 16: 2205-2215.
45. Isakova T, Gutierrez OM, Wolf M. A blueprint for randomized trials targeting phosphorus metabolism in chronic kidney disease. Kidney Int 2009; 76: 705-716.
46. Evenepoel P, Meijers B, Viaene L 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. Clin J Am Soc Nephrol 2010; 5: 1268-1276.
47. Isakova T, Wahl P, Vargas GS et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011; 79: 1370-1378.
48. Hasegawa H, Nagano N, Urakawa I 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 Int 2010; 78: 975-980.
49. John GB, Cheng CY, Kuro-o M. Role of Klotho in aging, phosphate metabolism, and CKD. Am J Kidney Dis 2011; 58: 127-134.
50. Kuro-o M. Klotho in chronic kidney disease-what's new? Nephrol Dial Transplant 2009; 24: 1705-1708.
51. Koh N, Fujimori T, Nishiguchi S et al. Severely reduced production of Klotho in human chronic renal failure kidney. Biochem Biophys Res Commun 2001; 280: 1015-1020.
52. Marsell R, Krajisnik T, Göransson H et al. Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-. 23. Nephrol Dial Transplant 2008; 23: 827-833.
53. Fliser D, Kollerits B, Neyer U et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol 2007; 18: 2600-2608.
54. Titan SM, Zatz R, Graciolli FG et al. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 2011; 6: 241-247.
55. Isakova T, Xie H, Yang W et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. J Am Med Assoc 2011; 305: 2432-2439.
56. Kendrick J, Cheung AK, Kaufman JS et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 2011; 22: 1913-1922.
57. Gutierrez OM, Mannstadt M, Isakova T et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359: 584-592.
58. Jean G, Terrat JC, Vanel T et al. 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.
59. Olauson H, Qureshi AR, Miyamoto T et al. Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship? Nephrol Dial Transplant 2010; 25: 3033-3038.
60. Seiler S, Reichart B, Roth D et al. FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transplant 2010; 25: 3983-3989.
61. Nakano C, Hamano T, Fujii N et al. Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis. Bone 2012; 50: 1266-1274.
62. Dhingra R, Sullivan LM, Fox CS et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 2007; 167: 879-885.
63. Larsson TE, Olauson H, Hagstrom E et al. Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community. Arterioscler Thromb Vasc Biol 2010; 30: 333-339.
64. Tonelli M, Curhan G, Pfeffer M et al. Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. Circulation 2009; 120: 1784-1792.
65. Tonelli M, Sacks F, Pfeffer M et al. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 2005; 112: 2627-2633.
66. Dobnig H, Pilz S, Scharnagl H et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008; 168: 1340-1349.
67. Parker BD, Schurgers LJ, Brandenburg VM et al. The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med 2010; 152: 640-648.
68. Taylor EN, Rimm EB, Stampfer MJ et al. Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease. Am Heart J 2011; 161: 956-962.
69. Semba RD, Fink JC, Sun K et al. Serum fibroblast growth factor-23 and risk of incident chronic kidney disease in older communitydwelling women. Clin J Am Soc Nephrol 2012; 7: 85-91.
70. Udell JA, O'Donnell T, Morrow D et al. Association of fibroblast growth factor (FGF)-23 levels with risk of cardiovascular events in patients with stable coronary artery disease. J Am Coll Cardiol 2012; 59: E1480.
71. Seiler S, Cremers B, Rebling NM et al. The phosphatonin fibroblast growth factor 23 links calcium-phosphate metabolism with left-ventricular dysfunction and atrial fibrillation. Eur Heart J 2011; 32: 2688-2696.
72. Ellam T, Wilkie M, Chamberlain J et al. Dietary phosphate modulates atherogenesis and insulin resistance in apolipoprotein E knockout mice-brief report. Arterioscler Thromb Vasc Biol 2011; 31: 1988-1990.
73. Jono S, McKee MD, Murry CE et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000; 87: E10-E17.
74. Neves KR, Graciolli FG, dos Reis LM et al. Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function, and bone in rats with renal failure. Kidney Int 2004; 66: 2237-2244.
75. Portale AA, Halloran BP, Morris RC Jr. Dietary intake of phosphorus modulates the circadian rhythm in serum concentration of phosphorus. Implications ofr the renal production of 1,25-dihydroxyvitamin D. J Clin Invest 1987; 80: 1147-1154.
76. American Diabetes Association. Standards of medical care in diabetes- 2009. Diabetes Care 2009; 32 (Suppl 1): S13-S61.
77. Faul C. Fibroblast growth factor 23 and the heart. Curr Opin Nephrol Hypertens 2012; 21: 369-375.
78. Gutierrez OM, Januzzi JL, Isakova T et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009; 119: 2545-2552.
79. Mirza MA, Larsson A, Melhus H et al. Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 2009; 207: 546-551.
80. Faul C, Amaral AP, Oskouei B et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011; 121: 4393-4408.
81. Frohlich ED, Apstein C, Chobanian AV et al. The heart in hypertension. N Engl J Med 1992; 327: 998-1008.
82. Levy D, Larson MG, Vasan RS et al. The progression from hypertension to congestive heart failure. J Am Med Assoc 1996; 275: 1557-1562.
83. Ellam TJ, Chico TJ. Phosphate: the new cholesterol? The role of the phosphate axis in non-uremic vascular disease. Atherosclerosis 2012; 220: 310-318.
84. Roos M, Lutz J, Salmhofer H et al. Relation between plasma fibroblast growth factor-23, serum fetuin-A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function. Clin Endocrinol (Oxf) 2008; 68: 660-665.
85. Mirza MA, Hansen T, Johansson L et al. Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant 2009; 24: 3125-3131.
86. Koiwa F, Kazama JJ, Tokumoto A et al. Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients. Ther Apher Dial 2005; 9: 336-339.
87. Nagano N, Miyata S, Abe M et al. Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Kidney Int 2006; 69: 531-537.
88. Pande S, Ritter CS, Rothstein M et al. FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation. Nephron Physiol 2006; 104: p23-p32