Intact Fibroblast Growth Factor 23 and Peripheral Vascular Complications in Patients on Hemodialysis

Year 2020, Volume: 47 Issue: 1, 66 - 73, 17.03.2020

Melahat Coban Ustun Yilmaz Suleyman Dolu Emre Asilturk Yıldızkilar Sozer Bekir Erol Hamit Yasar Ellidag

https://doi.org/10.5798/dicletip.706013

Abstract

Objective: Peripheral vascular complications frequently seen in hemodialysis patients are associated with mortality. Fibroblast growth factor 23 (FGF23) is thought to be a phosphaturic hormone that causes mortality in hemodialysis patients. The purpose of our study was to determine the association of intact FGF23 (I-FGF23) with atherosclerotic peripheral vascular complications in patients on hemodialysis.
Methods: This cross-sectional study was performed with 50 [28 (56%) male, 22 (44%) female] hemodialysis patients. Patient characteristics were compared with an age +- and sex-matched control group of 40 healthy volunteers. Atherosclerosis development was measured by carotid intima media thickness (CIMT) and arterial stiffness development was measured by brachial ankle pulse wave velocity (PWV) device.
Results: Increased atherosclerosis and arterial stiffness were observed in patients with high I-FGF23 and low alpha klotho (α-KL) levels compared to healthy subjects. I-FGF23 showed an inverse and independent relationship between lipid profile. There was no relationship between I-FGF23 and atherosclerosis and arterial stiffness.
Conclusion: There was no association between serum I-FGF23 and atherosclerotic peripheral vascular complications. The association between I-FGF23 and mortality may be due to cardiovascular events other than peripheral vascular complications in patients on hemodialysis.

Keywords

Atherosclerosis, arterial stiffness

References

• 1. Liu S, Gupta A, Quarles LD. Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization. CurrOpinNephrolHypertens 2007; 16: 329-35.
• 2. O'Leary DH, Polak JF. Intima-media thickness: a tool for atherosclerosis imaging and event prediction. Am J Cardiol 2002; 90: 18L-21L.
• 3. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974; 290: 697–701.
• 4. Balci M, Kirkpantur A, Gulbay M, Gurbuz A. Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients. HemodialInt 2010; 14: 425–32.
• 5. Turan MN, Kircelli F, Yaprak M, et al. FGF-23 levels are associated with vascular calcification, but not with atherosclerosis, in hemodialysis patients. IntUrolNephrol. 2016; 48: 609-17.
• 6. Mirza MA, Larsson A, Lind L, Larsson TE. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009; 205: 385-90.
• 7. Desjardins L, Liabeuf S, Renard C, et al. FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. OsteoporosInt 2012; 23: 2017-25.
• 8. 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: 1159-68.
• 9. Ibrahim WH, Ahmad AB, Sayed NG. Association of serum fibroblast growth factor-23 with Doppler pulse wave velocity in hemodialysis patients. Saudi J Kidney Dis Transpl 2018; 29: 95-100.
• 10. Wolf M, Molnar MZ, Amaral AP, et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am SocNephrol 2011; 22: 956–66.
• 11. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. ClinChem 1972; 18: 499-502.
• 12. Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: An analysis of error. J Am SocNephrol 1993; 4: 1205–13.
• 13. Homma S, Hirose N, Ishida H, Ishii T, Araki G. Carotid plaque and intima-media thickness assessed by B-mode ultrasonography in subjects ranging from young adults to centenarians. Stroke 2001; 32: 830-5.
• 14. Yokoyama H, Shoji T, Kimoto E, et al. Pulse wave velocity in lower-limb arteries among diabetic patients with peripheral arterial disease. J AtherosclerThromb 2003; 10: 253-8.
• 15. 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: 2792-6.
• 16. Hussein HS, Allam LE, Mohab A, Elbarghouty NM, Mohammed SY. Fibroblast Gross Factor-23 and Arterial Stiffness in Hemodialysis Patients. Int J ClinCardiol Res 2017; 1: 067-71.
• 17. Zeng Y, Feng S, Han OY, et al. Role of fibroblast growth factor-23 in the pathogenesis of atherosclerosis in peritoneal dialysis patients. Genet Mol Res 2015; 14: 719-29.
• 18. Inaba M, Okuno S, Imanishi Y, et al. Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients. OsteoporosInt 2006; 17: 1506-13.
• 19. Ashikaga E, Honda H, Suzuki H, et al. Impact of fibroblast growth factor 23 on lipids and atherosclerosis in hemodialysis patients. TherApher Dial 2010; 14: 315-22. 20. Park KA, Jo HM, Han JS, et al. Features of atherosclerosis in hemodialysis patients. Kidney Res ClinPract 2013; 32: 177-82.
• 21. Tomlinson E, Fu L, John L, et al. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity. Endocrinology 2002; 143: 1741-7.
• 22. Huang X, Yang C, Luo Y, et al. FGFR4 prevents hyperlipidemia and insulin resistance but underlies high-fat diet induced fatty liver. Diabetes 2007; 56: 2501-10.
• 23. Zhang F, Yu L, Lin X, et al. Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases. MolEndocrinol 2015; 29: 1400-13.
• 24. Jean G, Bresson E, Terrat JC, et al. Peripheral vascular calcifİcation in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 2009; 24: 948-55.
• 25. Manghat P, Souleimanova I, Cheung J, et al. Association of bone turnover markers and arterial stiffness in pre-dialysis chronic kidney disease (CKD). Bone 2011; 48: 1127-32.
• 26. Moldovan D, Moldovan I, Rusu C, et al. FGF-23, vascular calcification, and cardiovascular diseases in chronic hemodialysis patients. IntUrolNephrol 2014; 46: 121-8.
• 27. Shimada T, Kakitani M, Yamazaki Y, et al. Targeted ablation of FGF23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 2004; 113: 561-8.
• 28. Lindberg K, Olauson H, Amin R, et al. Arterial klotho expression and FGF23 effects on vascular calcification and function. PLoS One 2013; 8: e60658.
• 29. Tsuchikura S, Shoji T, Kimoto E, et al. Brachial-ankle pulse wave velocity as an index of central arterial stiffness. J AtherosclerThromb 2010; 17: 658-65.
• 30. Bernini G, Galetta F, Franzoni F, et al. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. J Hypertens 2008; 26: 2399-405.