SYSTEMIC DISORDERS OF INORGANIC PHOSPHATE EXCHANGE AS A NOVEL CLUSTER OF CARDIOVASCULAR RISK FACTORS
https://doi.org/10.18705/1607-419X-2014-20-6-478-491
Abstract
Recent studies have clearly linked higher serum inorganic phosphate (Pi) concentrations and an imbalance of Pi-regulation by kidney-bone-parathyroid endocrine systems to cardiovascular events and mortality. This association has been identified in patients with chronic kidney disease, as well as in general population. The editorial discusses the available clinical and experimental data linking the pathophysiology of phosphate exchange disorders and cardiovascular events.
About the Author
V. A. Dobronravov
First Pavlov State Medical University of St. Petersburg,St Petersburg
Russian Federation
Russian Federation
Сorresponding author:Vladimir A. Dobronravov,MD, PhD, DMSc, Professor, Research instituteof Nephrology, First Pavlov State Medical University of St. Petersburg, 17 L. Tolstoystreet, St Petersburg, 197022, Russia.Tel.: +7(812)234–66–56. E-mail: dobronravov@nephrolog.ru
References
1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD -MBD Work Group.KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease — Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113: S1-S130.
2. Smirnov AV, Shilov EM, Dobronravov VA et al. National guidelines. Chronic kidney disease: principles of screening, diagnostic, prophylaxis and approaches to treatment. Nephrologia. 2012;16(1):89–115. In Russian.
3. Smirnov AV, Dobronravov VA, Kaukov IG. The problem of chronic kidney disease in contemporary medicine. Arterial’naya Gipertenziya = Arterial Hypertension. 2006;12 (3):185–193. In Russian.
4. Gansevoort RT, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS et al. Chronic Kidney Disease Prognosis Consortium. Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and highrisk population cohorts. Kidney Int. 2011;80(1):93–104.
5. Perk J, De Backer G, Gohlke H et al. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–1701.
6. Smirnov AV, Dobronravov VA, Kaukov IG. The cardiorenal continuum: pathogenetic grounds of the preventive nephrology. Nephrologia. 2005;9(3):7–15. In Russian.
7. Kestenbaum B, Sampson JN, Rudser KD, PattersonDJ, Seliger SL, Young B et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005;16 (2):520–528.
8. McGovern AP, de Lusignan S, van Vlymen J, Liyanage H, Tomson CR, Gallagher H et al. Serum phosphate as a risk factor for cardiovascular events in people with and without chronic kidney disease: a large community based cohort study. PLoS One. 2013;8(9):e74996.
9. Kendrick J, Kestenbaum В, Chonchol М. Phosphate and cardiovascular disease. Adv Chronic Kidney Dis. 2011;18(2):113–119.
10. Blacher J, Asmar R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999;33(5):1111–1117.
11. Hollander M, Hak AE, Koudstaal PJ, Bots ML, Grobbee DE, Hofman A. Comparison between measures of atherosclerosis and risk of stroke: the Rotterdam Study. Stroke. 2003;34(10):2367–2372.
12. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR et al. Coronary calcium as a predictor of coronary eventsin four racial or ethnic groups. N Engl J Med. 2008;358 (13):1336–1345.
13. Olson JC, Edmundowicz D, Becker DJ, Kuller LH, Orchard TJ. Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women. Diabetes. 2000;49(9):1571–1578.
14. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in endstage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18(9):1731–1740.
15. Klassen PS, Lowrie EG, Reddan DN, DeLong ER, Coladonato JA, Szczech LA et al. Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis. J Am Med Assoc. 2002;287(12):1548–1555.
16. Hunt JL, Fairman R, Mitchell ME, Carpenter JP, Golden M, Khalapyan T. Bone formation in carotid plaques: a clinicopathological study. Stroke. 2002;33 (5):1214–1219.
17. Edmonds ME, Morrison N, Laws JW, Watkins PJ. Medial arterial calcification and diabetic neuropathy. Br Med J (Clin Res Ed). 1982;284(6320):928–930.
18. Micheletti RG, Fishbein GA, Currier JS, FishbeinMC. Monckeberg sclerosis revisited: a clarification of the histologic definition of Monckeberg sclerosis. Arch Pathol Lab Med. 2008;132(1):43–47.
19. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342(20):1478–1483.
20. Ix JH, De Boer IH, Peralta CA, Adeney KL, Duprez DA, Jenny NS et al. Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol. 2009;4(3):609–615.
21. Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS et al. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009;20(2):381–387.
22. Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA. Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol. 2009;20 (2):397–404.
23. Kendrick J, Ix JH, Targher G, Smits G, Chonchol M. Relation of serum phosphorus levels to ankle brachial pressure index (from the Third National Health and Nutrition Examination Survey). Am J Cardiol. 2010;106 (4):564–568.
24. Li JW, Xu C, Fan Y, Wang Y, Xiao YB. Can serum levels of alkaline phosphatase and phosphate predict cardiovascular diseases and total mortality in individuals with preserved renal function? A systemic review and metaanalysis. PLoS One. 2014;9(7): e102276.
25. Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC, Elder GJ et al. 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. J Am Med Assoc. 2011;305(11):1119–1127.
26. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561–1566.
27. Park M, Hsu CY, Li Y et al. Chronic RenalInsufficiency Cohort (CRIC) Study Group Associations between kidney function and subclinical cardiac abnormalitiesin CKD. J Am Soc Nephrol. 2012;23(10):1725–1734.
28. Levin A. Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis. Semin Dial. 2003;16(2):101–105.
29. Strozecki P, Adamowicz A, Nartowicz E, OdrowazSypniewska G, Wiodarczyk Z, Manitius J. Parathormone, calcium, phosphorus, and left ventricular structure and function in normotensive hemodialysis patients. Ren Fail 2001;23(1):115–126.
30. Galetta F, Cupisti A, Franzoni F, Morelli E, CaprioliR, Rindi P et al. Changes in heart rate variability in chronic uremic patients during ultrafiltration and hemodialysis. Blood Purif. 2001;19(4):395–400.
31. Culleton BF, Walsh M, Karenbach SW, Mortis G, Scott-Douglas N, Quinn RR et al. Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial. J Am Med Assoc. 2007;298(11):1291–1299.
32. Yamamoto KT, Robinson-Cohen C, de Oliveira MC, Kostina A, Nettleton JA, Ix JH et al. Dietary phosphorus is associated with greater left ventricular mass. Kidney Int. 2013;83(4):707–714.
33. Slinin Y, Foley RN, Collins AJ. Calcium, phosphorus, parathyroid hormone and cardiovascular disease in hemodialysis patients. The USRDS waves 1,3 and 4 study. J Am Soc Nephrol. 2005;16(6):1788–1793.
34. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in hemodialysis patients. J Am Soc Nephrol. 2004;15(8):2208–2218.
35. Chonchol M, Dale R, Schrier RW, Estacio R. Serum phosphorus and cardiovascular mortality in type 2 diabetes. Am J Med. 2009;122(4):380–386.
36. Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation. 2005;112(17):2627–2633.
37. Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007;167(9):879–885.
38. Foley RN, Collins AJ, Ishani A, Kalra PA. Calciumphosphate levels and cardiovascular disease in communityswelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156(3):556–563.
39. Hruska K, Mathew S, Lund R, Fang Y, Sugatani T. Cardiovascular risk factors in chronic kidney disease: does phosphate qualify? Kidney Int Suppl. 2011;79 (121): S9-S13.
40. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J 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(3):519–530.
41. Grandi NC, Brenner H, Hahmann H et al. Calcium, phosphate and the risk of cardiovascular events and all-cause mortality in a population with stable coronary heart disease. Heart. 2012;98(12):926–933.
42. Van Hemelrijck M, Michaelsson K, Linseisen J, Rohrmann S. Calcium intake and serum concentration in relation to risk of cardiovascular death in NHANES III. PLoS One. 2013;8(4): e61037.
43. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC — Heidelberg). Heart. 2012;98(12):920–925.
44. Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD et al. Effect of calcium supplements on risk of myocardialinfarction and cardiovascular events: meta-analysis. Br Med J. 2010;341: e3691.
45. Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R et al. Vascular events in healthy older women receiving calcium supplementation: randomized controlled trial. Br Med J. 2008;336(7638):262–266.
46. Wang X, Chen H, Ouyang Y, Liu J, Zhao G, Bao W et al. Dietary calcium intake and mortality risk from cardiovascular disease and all causes: a meta-analysis of prospective cohort studies. BMC Med. 2014;12(1):158.
47. Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013;4(5):199–210.
48. Sage AP, Lu J, Tintut Y, Demer LL. Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int. 2011;79 (4):414–422.
49. Villa-Bellosta R, Sorribas V. Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition. Arterioscler Thromb Vasc Biol. 2009;29(5):761–766.
50. Ewence AE, Bootman M, Roderick HL, SkepperJN, McCarthy G, Epple M et al. Calcium phosphate crystalsinduce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res. 2008;103(5): e28-e34.
51. Khoshniat S, Bourgine A, Julien M, Petit M, Pilet P, Rouillon T et al. Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium. Bone. 2010;48 (4):894–902.
52. Kuro-o M. Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nat Rev Nephrol. 2013;9 (11):650–660.
53. Smith ER, Ford ML, Tomlinson LA, Rajkumar C, McMahon LP, Holt SG. Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD. Nephrol Dial Transplant. 2012;27(5):1957–1966.
54. Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R et al. Smooth muscle cell phenotypic transition associated with calcification: up-regulation of Cbfa1 and down-regulation of smooth muscle lineage markers. Circ Res. 2001;89(12):1147–1154.
55. Speer MY, Li X, Hiremath PG, Giachelli CM. Runx2/Cbfa1. but not loss of myocardin, is required for smooth muscle cell lineage reprogramming toward osteochondrogenesis. J Cell Biochem. 2010;110(4):935–947.
56. Shioi ANY, Jono S, Koyama H, Hosoi M, Morii H. Beta-glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Throm Vasc Biol. 1995;15 (11):2003–2009.
57. Chen NX, O’Neill KD, Duan D, Moe SM. Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. Kidney Int. 2002;62(5):1724–1731.
58. Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol. 2008;19(6):1092–1105.
59. Gittenberger-de Groot AC, Winter EM, Bartelings MM, Goumans MJ, DeRuiter MC, Poelmann RE. The arterial and cardiac epicardium in development, disease and repair. Differentiation. 2012;84(1):41–53.
60. Von Gise A, Pu WT. Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease. Circ Res. 2012;110(12):1628–1645.
61. Mill C, George SJ. Wnt signalling in smooth muscle cells and its role in cardiovascular disorders. Cardiovasc Res. 2012;95(2):233–240.
62. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J. Augmented Wnt signaling in a mammalian model of accelerated aging. Science. 2007;317(5839):803–806.
63. Kawakami T, Ren S, Duffield JS. Wnt signalling in kidney diseases: dual rolesin renal injury and repair. J Pathol. 2013;229(2):221–231.
64. Kamiya N, Kobayashi T, Mochida Y, Yu PB, Yamauchi M, Kronenberg HM et al. Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts. J Bone Miner Res. 2010;25(2):200–210.
65. Ueland T, Otterdal K, Lekva T, Halvorsen B, Gabrielsen A, Sandberg WJ et al. Dickkopf-1 enhances in flammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29(8):1228–1234.
66. Sabbagh Y, Graciolli FG, O’Brien S, Tang W, dos Reis LM, Ryan S et al. Repression of osteocyte Wnt/β- catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res. 2012;27(8):1757– 1772.
67. Li X, Yang HY, Giachelli CM. BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis. 2008;199(2):271–277.
68. Cheng SL, Shao JS, Behrmann A, Krchma K, Towler DA. Dkk1 and MSX2‑Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33 (7):1679–1689.
69. Askevold ET, Gullestad L, Aakhus S, Ranheim T, Tønnessen T, Solberg OG et al. Secreted Wnt modulators in symptomatic aortic stenosis. J Am Heart Assoc. 2012;1(6): e002261.
70. Garcia-Martín A, Reyes-Garcia R, García-FontanaB, Morales-Santana S, Coto-Montes A, Muñoz-Garach M et al. Relationship of Dickkopf1 (DKK1) with Cardiovascular Disease and Bone Metabolism in Caucasian Type 2 Diabetes Mellitus. PLoS One. 2014;9(11): e111703.
71. Wang L, Hu XB, Zhang W, Wu LD, Liu YS, Hu B et al. Dickkopf-1 as a novel predictor is associated with risk stratification by GRACE risk scores for predictive value in patients with acute coronary syndrome: a retrospective research. PLoS One. 2013;8(1): e54731.
72. Fang Y, Ginsberg C, Seifert M, Agapova O, SugataniT, Register TC et al. CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD -Mineral and Bone Disorder. J Am Soc Nephrol. 2014;25(8):1760–1773.
73. Dobronravov VA. Modern view on the pathogenesis of the secondary hyperparathyreosis: the role of fibroblast growth factor and Klotho. Nephrologia. 2011;15(4):11–20. In Russian.
74. Smirnov AV, Volkov MM, Dobronravov VA. C ardioprotective effects of D-hormone in patients with chronic kidney disease: literature review and personal data. Nephrologia. 2009;13(1):30–38. In Russian.
75. Nigwekar SU, Thadhani R. Vitamin D receptor activation: cardiovascular and renal implications. Kidney Int Suppl (2011). 2013;3 5):427–430.
76. Li YC. Vitamin D: rolesin renal and cardiovascular protection. Curr Opin Nephrol Hypertens. 2012;21(1): 72–79.
77. Weishaar RE, Kim SN, Saunders DE, Simspon RU. Involvement of vitamin D3 with cardiovascular function. III. Effects on physical and morphological properties. Am J Physiol. 1990;258(1 Pt. 1): E134-E142.
78. Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W et al. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab. 2005;288 (1):125–132.
79. Mathew S, Lund RJ, Chaudhary LR, Geurs T, Hruska KA. Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol. 2008;19 (8):1509–1519.
80. Mizobuchi M, Finch JL, Martin DR, Ststopolsky E. Differential effects of vitamin D receptor activators on vascular calcification in uremic rats. Kidney Int. 2007;72 (6):709–715.
81. Kokot F, Pietrek J, Srokowska S, Wartenberg W, Kuska J, Jedrychowska M et al. 25-hydroxyvitamin D in patients with essential hypertension. Clin Nephrol. 1981;16 (4):188–192.
82. Burgaz A, Orsini N, Larsson SC, Wolk A. Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J Hypertens. 2011;29(4):636–645.
83. Pilz S, Marz W, Wellnitz B, Seelhorst U, FahrleitnerPammer A, Dimai HP et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large crosssectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008;93(10):3927–3935.
84. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–511.
85. Pilz S, Iodice S, Zittermann A, Grant WB, Grandini S. Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis. 2011;58(3):374–382.
86. Drechsler C, Verduijn M, Pilz S, Dekker FW, Krediet RT, Ritz E et al. Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant. 2011;26 (3):1024–1032.
87. Abu el Maaty MA, Gad MZ. Vitamin D deficiency and cardiovascular disease: potential mechanisms and novel perspectives. J Nutr Sci Vitaminol (Tokyo). 2013;59 (6):479–488.
88. Clemens TL, Cormier S, Eichinger A, Endlich K, Fiaschi-Taesch N, Fischer E et al. Parathyroid hormonerelated protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets. Br J Pharmacol. 2001;134(6):1113–1136.
89. Goettsch C, Iwata H, Aikawa E. Parathyroid hormone: critical bridge between bone metabolism and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2014;34(7):1333–1335.
90. Macfarlane DP, Yu N, Leese GP. Subclinical and asymptomatic parathyroid disease: implications of emerging data. Lancet Diabetes Endocrinol. 2013;1(4):329–340.
91. Bosworth C, Sachs MC, Duprez D, Hoofnagle AN, Ix JH, Jacobs DR Jr et al. Parathyroid hormone and arterial dysfunction in the multi-ethnic study of atherosclerosis. Clin Endocrinol (Oxf). 2013;79(3):429–436.
92. Hagström E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundström J et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119(21):2765–2771.
93. Нagström E, Michaëlsson K, Melhus H, Hansen T, Ahlström H, Johansson L et al. Plasma-parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts. Arterioscler Thromb Vasc Biol. 2014;34(7):1567–1573.
94. Nakayama K, Nakao K, Takatori Y, Inoue J, Kojo S, Akagi S et al. Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism. Int J Nephrol Renovasc Dis. 2013;7:25–33.
95. Tomaschitz A, Ritz E, Pieske B, Rus-Machan J, Kienreich K, Verheyen N et al. Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease. Metabolism. 2014;63(1):20–31.
96. Gutierrez OM, Wolf M, Taylor EN. Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the Health Professionals Follow -up Study. Clin J Am Soc Nephrol. 2011;6(12):2871–2878.
97. Manghat P, Fraser WD, Wierzbicki AS, Fogelman I, Goldsmith DJ, Hampson G. Fibroblast growth factor-23 is associated with C-reactive protein, serum phosphate and bone mineral density in chronic kidney disease. Osteoporos Int. 2010;21(11):1853–1861.
98. Isakova T, Xie H, Yang W et al. Chronic Renal Insufficiency Cohort (CRIC) Study Group: 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 23):2432–2439.
99. Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A 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(9):2600–2608.
100. Wolf M, Molnar MZ, Amaral AP, Czira ME, Rudas A, Ujszaszi A et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol. 2011;22(5):956–966.
101. Gutiérrez OM, Mannstadt M, Isakova T, RauhHain JA, Tamez H, Shah A et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359(6):584–592.
102. Lundberg S, Qureshi AR, Olivecrona S, GunnarssonI, Jacobson SH, Larsson TE. FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy. Clin J Am Soc Nephrol. 2012;7(5):727–734.
103. Ix JH, Katz R, Kestenbaum BR, de Boer IH, Chonchol M, Mukamal KJ et al. Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study). J Am Coll Cardiol. 2012;60(3):200–207.
104. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L et al. Higher fibroblast growth factor‑23 increases the risk of all-cause and cardiovascular mortality in the community. Kidney Int. 2013;83(1):160–166.
105. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L et al. Serum FGF23 and Risk of Cardiovascular Events in Relation to Mineral Metabolism and Cardiovascular Pathology. Clin J Am Soc Nephrol. 2013;8(5):781–786.
106. Jovanovich A, Ix JH, Gottdiener J, McFann K, Katz R, Kestenbaum B et al. Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults. Atherosclerosis. 2013;231 (1):114–119.
107. Scialla JJ, Xie H, Rahman M, Anderson AH, Isakova T, Ojo A et al. Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2014;25 (2):349–360.
108. Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121(11):4393–4408.
109. Shibata K, Fujita S, Morita H, Okamoto Y, Sohmiya K, Hoshiga M et al. Association between circulating fibroblast growth factor 23, α-Klotho, and the left ventricular ejection fraction and left ventricular mass in cardiology inpatients. PLoS One. 2013;8(9): e73184.
110. Seifert ME, de Las Fuentes L, Ginsberg C, Rothstein M, Dietzen DJ, Cheng SC et al. Left ventricular mass progression despite stable blood pressure and kidney function in stage 3 chronic kidney disease. Am J Nephrol. 2014;39(5):392–399.
111. Seiler S, Rogacev KS, Roth HJ, Shafein P, Emrich I, Neuhaus S et al. Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2–4. Clin J Am Soc Nephrol. 2014;9(6):1049–1058.
112. Molkentin JD, Lu J, Antos C, Markham B, Richardson J, Robbins J et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93(2):215–228.
113. Komuro I, Yazaki Y. Control of cardiac gene expression by mechanical stress. Annu Rev Physiol. 1993;55:55–75.
114. Itoh N, Ohta H. Pathophysiological roles of FGF signaling in the heart. Front Physiol. 2013;4:247.
115. Kendrick J, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol. 2011;22(10):1913–1922.
116. Seiler S, Reichart B, Roth D, Seibert E, Fliser D, Heine GH et al. FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transplant. 2010;25 (12):3983–3989.
117. Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M 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(10):640–648.
118. Taylor EN, Rimm EB, Stampfer MJ, Curhan GC. Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease. Am Heart J. 2011;161(5):956–962.
119. Srivaths PR, Goldstein SL, Silverstein DM, Krishnamurthy R, Brewer ED. Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients. Pediatr Nephrol. 2011;26(6):945–991.
120. Roos M, Lutz J, Salmhofer H, Luppa P, Knauss A, Braun S 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(4):660–665.
121. Mirza MA, Larsson A, Lind L, Larsson TE. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis. 2009;205(2):385–390.
122. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T et al. Mutation of the mouse Klotho gene leads to a syndrome resembling ageing. Nature. 1997;390 (6655):45–51.
123. Kuro-o М. Phosphate and klotho. Kidney Int. 2011;79(121): S20-S23.
124. Dai B, David V, Martin A, Huang J, Li H, Jiao Y et al. A comparative transcriptome analysis identifying FGF23 regulated genesin the kidney of a mouse CKD model. PLoS One. 2012;7(9): e44161.
125. Lim K, Lu T.S, Molostvov G, Lee C, Lam FT, Zehnder D et al. Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation. 2012;125(18):2243–2255.
126. VanVenrooij NA, Pereira RC, Tintut Y, FishbeinMC, Tumber N, Demer LL et al. FGF23 protein expression in coronary arteriesis associated with impaired kidney function. Nephrol Dial Transplant. 2014;29(8):1525–1532.
127. Navarro-González JF, Donate-Correa J, Muros de Fuentes M, Pérez-Hernández H, Martínez-Sanz R, MoraFernández C. Reduced Klotho is associated with the presence and severity of coronary artery disease. Heart. 2014;100 (1):34–40.
128. Hu MC, Shi M, Zhang J, Quiñones H, Griffith C, Kuro-o M et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2011;22(1):124–136.
129. Zhao Y, Banerjee S, Dey N, LeJeune WS, Sarkar PS, Brobey R et al. Klotho depletion contributes to increased inflammation in kidney of the db/db mouse model of diabetes via RelA (serine)536 phosphorylation. Diabetes. 2011;60(7):1907–1916.
130. Hu MC, Kuro-o M, Moe OW. Secreted klotho and chronic kidney disease. Adv Exp Med Biol. 2012;728:126– 157.
131. De Oliveira RM. Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway. FEBS Lett. 2006;580(24):5753–5758.
132. Nakano-Kurimoto R, Ikeda K, Uraoka M, Nakagawa Y, Yutaka K, Koide M et al. Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition. Am J Physiol Heart Circ Physiol. 2009;297(5):1673–1684.
133. Kuroo M. Klotho as a regulator of oxidative stress and senescence. Biol Chem. 2008;389(3):233–241.
134. Kusaba T, Okigawa M, Matui A, Murakami M, Ishikawa K, Kimura T et al. Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci USA. 2010;107(45):19308–19313.
135. Nagai R, Saito Y, Ohyama Y, Aizawa H, Suga T, Nakamura T et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci. 2000;57(5):738–746.
136. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P et al. Suppression of aging in mice by the hormone Klotho. Science. 2005;309(5742):1829–1833.
137. Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L et al. Klotho inhibits transforming growth factorbeta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 2011;286 (10):8655–8665.
138. Takeshita K, Fujimori T, Kurotaki Y, Honjo H, Tsujikawa H, Yasui K et al. Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression. Circulation. 2004;109(14):1776–1782.
139. Nowak A, Friedrich B, Artunc F, Serra AL, Breidthardt T, Twerenbold R et al. Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients. PLoS One. 2014;9(7): e100688.
140. Six I, Okazaki H, Gross P, Cagnard J, Boudot C, Maizel J et al. Direct, acute effects of Klotho and FGF23 on vascular smooth muscle and endothelium. PLoS One. 2014;9 (4): e93423.
141. Bogdanova EO, Beresneva ON, Semenova NY et al. Renal αklotho expression is associated with myocardial hypertrophy in spontaneously hypertensive rats (experimental study). Arterial’naya Gipertenziya = Arterial Hypertension. 2014;20(6): [In press]. In Russian.
142. Xie J, Cha SK, An SW, Kuro-o M, Birnbaumer L, Huang CL. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart. Nat Commun. 2012;3:1238.
143. Hu MC, Shi M, Cho HJ, Adams-Huet B, Paek J, Hill K et al. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol. 2015;26(6):1290–302.
144. Song S, Gao P, Xiao H, Xu Y, Si LY. Klotho suppresses cardiomyocyte apoptosis in mice with stressinduced cardiac injury via downregulation of endoplasmic reticulum stress. PLoS One. 2013;8(12): e82968.
145. Maekawa Y, Ohishi M, Ikushima M, Yamamoto K, Yasuda O, Oguro R et al. Klotho protein diminishes endothelial apoptosis and senescence via a mitogenactivated kinase pathway. Geriatr Gerontol Int. 2011;11 (4):510–516.
146. Liu F, Wu S, Ren H, Gu J. Klotho suppresses RIGI‑mediated senescence -associated inflammation. Nat Cell Biol. 2011;13(3):254–262.
147. Fang Y, Ginsberg C, Sugatani T, MonierFaugere MC, Malluche H, Hruska KA. Early chronic kidney disease — mineral bone disorder stimulates vascular calcification. Kidney Int. 2014;85(1):142–150.
148. Kim HR, Nam BY, Kim DW, Kang MW, Han JH, Lee MJ et al. Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis. 2013;61 (6):899–909.
Review
For citations:
Dobronravov V.A. SYSTEMIC DISORDERS OF INORGANIC PHOSPHATE EXCHANGE AS A NOVEL CLUSTER OF CARDIOVASCULAR RISK FACTORS. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2014;20(6):478-491. https://doi.org/10.18705/1607-419X-2014-20-6-478-491
Views:
1128
Email this article 