Fibroblast growth factor 23 and a novel high-sensitivity troponin I: Early markers and alternative ways of damaging the heart in chronic kidney disease


Cite item

Full Text

Abstract

Aim. To establish possible pathogenetic relationships between the marker of bone mineral metabolism fibroblast growth factor 23 (FGF-23) and the markers of cardiovascular diseases characterizing the state of cardiomyocytes and that of the vascular wall of the aorta and large vessels in chronic kidney disease (CKD). Subjects and methods. A total of 110 patients (57 men and 53 women) aged 25 to 65 years (mean age 56±2.2 years) with different stages of CKD were examined. FGF-23 and troponin I in the sera from all the patients were investigated using enzyme immunoassay kits. Doppler echocardiography was carried out to evaluate the morphofunctional state of the left ventricle (LV). Peak systolic blood flow velocity in the aortic arch and common carotid intima-media thickness were estimated to assess the wall of the aorta and large arteries. Results. As renal failure progressed, just at the early CKD stages the patients were found to have elevating FGF-23 and troponin I levels forestalling an increase in parathyroid hormone concentrations and changes in other calcium-phosphorus metabolism indicators. The levels of FGF-23 and the morphofunctional indicators of LV lesion showed a strong direct correlation that preserved its significance in analyzing the factors under study in relation to the function of the kidneys. Conclusion. The morphogenetic protein FGF-23 seems to play a significant role not only in bone remodeling processes, but also in the development of cardiovascular events in CKD. However, the mechanisms of its implication in the development of heart disease, like the possibilities of using its level changes as early diagnostic criteria for cardiovascular involvement, call for further investigation.

References

  1. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Jüppner H, Wolf M. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584-592. doi: 10.1056/nejmoa0706130.
  2. Jean G, Terrat JC, Vanel T, Hurot JM, 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. doi: 10.1093/ndt/gfp191.
  3. Kendrick J, Cheung AK, Kaufman JS, Greene T, Roberts WL, 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. doi: 10.1681/asn.2010121224.
  4. Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M; 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. JAMA. 2011;305:2432-2439. doi: 10.1001/jama.2011.826.
  5. Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M, Shlipak MG, Whooley MA, Ix JH. 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. doi: 10.7326/0003-4819-152-10-201005180-00004.
  6. Cozzolino M, Cosa F, Ciceri F Vascular calcification in chronic kidney disease. EMJ Neph. 2013;1:46-51.
  7. Смирнов А.В. Системный подход к анализу кардиоренальных взаимоотношений как первый шаг на пути к нефрологии формата П4. Нефрология. 2011;15(2):11-19.
  8. Inoue N, Maeda R, Kavakami H, Shokawa T, Yamamoto H, Ito C, Sasaki H. Aortic pulse wave velocity predicts cardiovascular mortality in middle-aged and elderly Japanese men. Circ J. 2009;73:549-553.
  9. Shave R, Baggish A, George K, Wood M, Scharhag J, Whyte G, Gaze D, Thompson PD. Exercise-induced cardiac troponin elevation: evidence, mechanisms, and implication. J Am Coll Cardiol. 2010;56:169-176. doi: 10.1016/j.jacc.2010.03.037.
  10. Kanbay M, Nicoleta M, Selcoki Y, Ikizek M, Aydin M, Eryonucu B, Duranay M, Akcay A, Armutcu F, Covic A. Fibroblast growght factor-23 and fetuin A are independent predictors for coronary artery disease extent in mild chronic kidney disease. Clin J Am SocNephrol. 2010;5:1780-1786. doi: 10.2215/cjn.02560310.
  11. Bhuriya R, Li S, Chen SC, McCullough PA, Bakris GL. Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD stages 3 and 4: an analysis s from the Kidney Early Evaluation Program (KEEP). Am J K Kidney Dis. 2009;53(Suppl 4):S3-S10. doi: 10.1053/j.ajkd.2008.11.029.
  12. Wolf M. Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol. 2010;21:1427-1435.
  13. Di Marco GS, König M, Stock C, Wiesinger A, Hillebrand U, Reiermann S, Reuter S, Amler S, Köhler G, Buck F, Fobker M, Kümpers P, Oberleithner H, Hausberg M, Lang D, Pavenstädt H, Brand M. High phosphate directly affects endothelial function by downregulating annexin II. Kidney Int. 2013;83:213-222. doi: 10.1038/ki.2012.300.
  14. Дзгоева Ф.У., Гатагонова Т.М., Бестаева Т.Л. и др. Остеопротегерин и фактор роста фибробластов (FGF-23) в развитии кардиоваскулярных осложнений при хронической болезни почек. Терапевтический архив. 2014;6:63-69.
  15. Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutiérrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro-O M, Kusek JW, Keane MG, Wolf M. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393-4408. doi: 10.1172/jci46122.
  16. Мухин Н.А. Хроническая болезнь почек. Клиническая фармакологияи терапия. 2011;4:70-75.
  17. Батюшин М.М., Левицкая Е.С., Терентьев В.П. Оценка влияния «почечных» факторов риска и параметров коронарной бляшки на сердечно-сосудистый прогноз у больных с ишемической болезнью сердца. Кардиоваскулярная терапия и профилактика. 2011;4:59-62.
  18. Милованова Л.Ю., Милованов Ю.С., Козловская Л.В., Мухин Н.А. Новые маркеры кардиоренальных взаимосвязей при хронической болезни почек. Терапевтический архив. 2013;6:17-24.
  19. Mirza MA, Larsson A, Lind L, Larsson TE. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis. 2009;205:385-390. doi: 10.1016/j.atherosclerosis.2009.01.001.
  20. 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. doi: 10.1038/ki.2013.332.
  21. Scialla JJ, Lau WL, Reilly MP, et al. Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney Int. 2013;83:1159-1168.
  22. Chertow GM, Block GA, Correa-Rotter R, Isakova T, Yang HY, Crouthamel MH, Chavkin NW, Rahman M, Wahl P, Amaral AP, Hamano T, Master SR, Nessel L, Chai B, Xie D, Kallem RR, Chen J, Lash JP, Kusek JW, Budoff MJ, Giachelli CM, Wolf M; Chronic Renal Insufficiency Cohort Study Investigators. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl JMed. 2012;367:2482-2494. doi: 10.1038/ki.2013.3.
  23. Mathew JS,Sachs MC, Katz R, Patton KK, Heckbert SR, Hoofnagle AN, Alonso A, Chonchol M, Deo R, Ix JH, Siscovick DS, Kestenbaum B, de Boer IH. Fibroblast growth factor-23 and incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Circulation. 2014;130:298-307. doi: 10.1161/circulationaha.113.005499.
  24. Добронравов В.А. Современный взгляд на патофизиологию вторичного гиперпаратиреоза: Роль фактора роста фибробластов-23 и Klotho. Нефрология. 2011;4:11-20.
  25. Hsu JJ, Katz R, Ix J. Association of fibroblast growth factor-23 with arterial stiffness in the Multiethnic Study of Atherosclerosis (MESA). Nephrol Dial Transplant. 2014;29:2099-2105.
  26. Shave R, Baggish A, George K, Wood M, Scharhag J, Whyte G, Gaze D, Thompson PD. Exercise-induced cardiac troponin elevation: evidence, mechanisms, and implication. J Am Coll Cardiol. 2010;56:169-176. doi: 10.1016/j.jacc.2010.03.037.
  27. Lemos JA, Drazner MH, Omland Τ, Ayers CR, Khera A, Rohatgi A, Hashim I, Berry JD, Das SR, Morrow DA, McGuire DK. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304:2503-2512. doi: 10.1001/jama.2010.1768.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2015 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

 © 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies