Yıl 2019, Cilt 5 , Sayı 5, Sayfalar 836 - 846 2019-09-04

The evaluation of the relationship between fetuin-A and traditional and non-traditional cardiovascular risk factors in kidney transplantation recipients

Nizameddin KOCA [1] , Alparslan ERSOY [2] , Barış ŞENSOY [3] , Emine KIRHAN [4] , Sümeyye GÜLLÜLÜ [5] , Melahat DİRİCAN [6] , Emre SARANDÖL [7]

Objectives: Kidney transplantation recipients (KTRs) have higher cardiovascular complications risk compared to the general population. Cardiovascular risk factors (CVRF, Traditional and non-traditional) are widely studied to understand the causes of increased cardiovascular disease (CVD) risk in KTRs. Fetuin-A prevents from vascular calcification (VC) by inhibiting production and collapsing of apatite crystals to the vascular wall. The relationship between fetuin-A levels and CVRF in KTRs was investigated in this study.

Methods: Sixty-two KTRs with no prior CVD history participated. Anthropometrical, laboratory (fetuin-A, inflammation markers, antioxidants, lipid peroxidation products) and cardiological (echocardiographic, pulse wave velocity) measurements were performed. Participants were divided into two groups according to normal (≥ 0.5 g/L, n = 32, NFA) and low (< 0.5 g/L, n = 30, LFA) fetuin-A levels according to manufacturer’s reference range, and the results were compared.

Results: No significant difference was observed in demographic features, body mass index, systolic and diastolic blood pressures, left ventricle mass index, waist and hip circumferences, left ventricle hypertrophy and waist-hip ratios between the two groups (p > 0.05). The ratios of drug usage such as immunosuppressives, anti-hypertensives and statin were comparable between two groups. Parathormone levels were significantly higher in the NFA group (p = 0.015) and glomerular filtration rate was calculated significantly higher in LFA group (p = 007). The comparison of other CVRF reveals no significant difference (p > 0.05).

Conclusions: Although many CVRF improved in KTRs, subclinical inflammation markers were still higher than the healthy population. Identification and early recognition of CVRF in high-risk individuals may contribute to the reduction of cardiovascular mortality. In our study, we observed no significant relationship between fetuin-A levels and CVRFs. We evaluated the relationship between serum fetuin-A levels on cardiovascular risk factors by its role in pathophysiology. 

Kidney transplantation, cardiovascular risk factor, fetuin-A
  • [1] Foley RN, Parfrey PS. Cardiovascular disease and mortality in ESRD. J Nephrol 1998;11:239-45.
  • [2] Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant 2004;4:1662-8.
  • [3] Kolonko A, Chudek J, Szotowska M, Kuczera P, Wiecek A. Cardiovascular risk factors and markers of atherosclerosis in stable kidney transplant recipients. Transplant Proc 2016;48:1543-50.
  • [4] Yilmaz MI, Sonmez A, Saglam M, Cayci T, Kilic S, Unal HU, et al. A longitudinal study of inflammation, CKD-mineral bone disorder, and carotid atherosclerosis after renal transplantation. Clin J Am Soc Nephrol 2015;10:471-9.
  • [5] Sharaf El Din UA, Salem MM, Abdulazim DO. Vascular calcification: When should we interfere in chronic kidney disease patients and how? World J Nephrol 2016;5:398-417.
  • [6] Ioannou K, Stel VS, Dounousi E, Jager KJ, Papagianni A, Pappas K, et al. Inflammation, endothelial dysfunction and increased left ventricular mass in chronic kidney disease (CKD) patients: a longitudinal study. PLoS One 2015;10:e0138461.
  • [7] Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, et al. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005;20:1676-85.
  • [8] Guerin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000;15:1014-21.
  • [9] Yildiz A, Fazlioglu M, Ersoy A, Gullulu M, Gullulu S, Yurtkuran M. Arterial elasticity measurement in renal transplant recipients. Transplant Proc 2007;39:1455-7.
  • [10] Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003;361:827-33.
  • [11] Cheung AK, Sarnak MJ, Yan G, Dwyer JT, Heyka RJ, Rocco MV, et al. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int 2000;58:353-62.
  • [12] WHO. BMI classification 20.03.2018. Available from: http://apps.who.int/bmi/index.jsp?introPage=intro_3.html.
  • [13] Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977;55:613-8.
  • [14] Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12.
  • [15] Joist H, Brennan DC, Coyne DW. Anemia in the kidney-transplant patient. Adv Chronic Kidney Dis 2006;13:4-10.
  • [16] Lebreton JP, Joisel F, Raoult JP, Lannuzel B, Rogez JP, Humbert G. Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant. J Clin Invest 1979;64:1118-29.
  • [17] Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317:1098.
  • [18] Caglar K, Yilmaz MI, Saglam M, Cakir E, Kilic S, Eyileten T, et al. Endothelial dysfunction and fetuin A levels before and after kidney transplantation. Transplantation 2007;83:392-7.
  • [19] Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, et al. Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol 2005;16:1494-500.
  • [20] Kiberd B, Keough-Ryan T, Panek R. Cardiovascular disease reduction in the outpatient kidney transplant clinic. Am J Transplant 2003;3:1393-9.
  • [21] Ix JH, Chertow GM, Shlipak MG, Brandenburg VM, Ketteler M, Whooley MA. Fetuin-A and kidney function in persons with coronary artery disease--data from the Heart and Soul Study. Nephrol Dial Transplant 2006;21:2144-51.
  • [22] Mark PB, Murphy K, Mohammed AS, Morris ST, Jardine AG. Endothelial dysfunction in renal transplant recipients. Transplant Proc 2005;37:3805-7.
  • [23] Mercanoglu F, Turkmen A, Kocaman O, Pinarbasi B, Dursun M, Selcukbiricik F, et al. Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels. Transplant Proc 2004;36:1357-60.
  • [24] Passauer J, Büssemaker E, Lassig G, Gross P. Kidney transplantation improves endothelium-dependent vasodilation in patients with endstage renal disease. Transplantation 2003;75:1907-10.
  • [25] Roos M, Heinemann FM, Lindemann M, Horn PA, Lutz J, Stock K, et al. Fetuin-A pretransplant serum levels, kidney allograft function and rejection episodes: a 3-year posttransplantation follow-up. Kidney Blood Press Res 2011;34:328-33.
  • [26] Marechal C, Schlieper G, Nguyen P, Kruger T, Coche E, Robert A, et al. Serum fetuin-A levels are associated with vascular calcifications and predict cardiovascular events in renal transplant recipients. Clin J Am Soc Nephrol 2011;6:974-85.
  • [27] Cianciolo G, Capelli I, Angelini ML, Valentini C, Baraldi O, Scolari MP, et al. Importance of vascular calcification in kidney transplant recipients. Am J Nephrol 2014;39:418-26.
  • [28] Min JK, Lin FY, Gidseg DS, Weinsaft JW, Berman DS, Shaw LJ, et al. Determinants of coronary calcium conversion among patients with a normal coronary calcium scan: what is the "warranty period" for remaining normal? J Am Coll Cardiol 2010;55:1110-7.
  • [29] McCullough PA. Annual progression of coronary calcification in trials of preventive therapies. Arch Intern Med 2009;169:2064-70.
  • [30] Nickel T, Schlichting CL, Weis M. Drugs modulating endothelial function after transplantation. Transplantation 2006;82(1 Suppl):S41-6.
  • [31] Westenfeld R, Schlieper G, Woltje M, Gawlik A, Brandenburg V, Rutkowski P, et al. Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis--implications for post-transplantation bone disease. Nephrol Dial Transplant 2011;26:4115-23.
  • [32] Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003;112:357-66.
  • [33] Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-18.
  • [34] Sigrist MK, Taal MW, Bungay P, McIntyre CW. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol 2007;2:1241-8.
  • [35] Sumida Y, Nakayama M, Nagata M, Nakashita S, Suehiro T, Kaizu Y, et al. Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease. Clin Nephrol 2010;73:360-9.
  • [36] Ombrellino M, Wang H, Yang H, Zhang M, Vishnubhakat J, Frazier A, et al. Fetuin, a negative acute phase protein, attenuates TNF synthesis and the innate inflammatory response to carrageenan. Shock 2001;15:181-5.
  • [37] Goldfarb-Rumyantzev AS, Naiman N. Genetic predictors of acute renal transplant rejection. Nephrol Dial Transplant 2010;25:1039-47.
  • [38] Dervisoglu E, Kir HM, Kalender B, Caglayan C, Eraldemir C. Serum fetuin--a concentrations are inversely related to cytokine concentrations in patients with chronic renal failure. Cytokine 2008;44:323-7.
  • [39] Heiss A, DuChesne A, Denecke B, Grotzinger J, Yamamoto K, Renne T, et al. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 2003;278:13333-41.
  • [40] Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 2001;31:509-19.
  • [41] Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM. Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 2003;23:489-94.
  • [42] Cozzolino M, Galassi A, Biondi ML, Turri O, Papagni S, Mongelli N, et al. Serum fetuin-A levels link inflammation and cardiovascular calcification in hemodialysis patients. Am J Nephrol 2006;26:423-9.
  • [43] El-Shehaby AM, Zakaria A, El-Khatib M, Mostafa N. Association of fetuin-A and cardiac calcification and inflammation levels in hemodialysis patients. Scand J Clin Lab Invest 2010;70:575-82.
  • [44] van Summeren MJ, Hameleers JM, Schurgers LJ, Hoeks AP, Uiterwaal CS, Kruger T, et al. Circulating calcification inhibitors and vascular properties in children after renal transplantation. Pediatr Nephrol 2008;23:985-93.
  • [45] Kuzniar J, Porazko T, Klinger M. Relationship between fetuin-A concentration, elevated levels of inflammatory markers, and arterial wall stiffness in end-stage kidney disease. J Ren Nutr 2008;18:83-6.
Birincil Dil en
Konular Biyokimya ve Moleküler Biyoloji, Kalp ve Kalp Damar Sistemi, Transplantasyon, Üroloji ve Nefroloji
Bölüm Original Article

Orcid: 0000-0003-1457-4366
Yazar: Nizameddin KOCA (Sorumlu Yazar)
Kurum: Department of Internal Medicine, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
Ülke: Turkey

Orcid: 0000-0002-0710-0923
Yazar: Alparslan ERSOY
Kurum: Department of Nephrology & Transplantation, Uludağ University School of Medicine, Bursa, Turkey
Ülke: Turkey

Orcid: 0000-0003-0066-9946
Yazar: Barış ŞENSOY
Kurum: Department of Cardiology, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
Ülke: Turkey

Orcid: 0000-0003-1521-9366
Yazar: Emine KIRHAN
Kurum: Department of Biochemistry, Tavşanlı State Hospital, Kütahya, Turkey
Ülke: Turkey

Orcid: 0000-0003-2831-002X
Yazar: Sümeyye GÜLLÜLÜ
Kurum: Department of Cardiology, Uludağ University School of Medicine, Bursa, Turkey
Ülke: Turkey

Orcid: 0000-0002-4956-5278
Yazar: Melahat DİRİCAN
Kurum: Department of Biochemistry, Uludağ University School of Medicine, Bursa, Turkey
Ülke: Turkey

Orcid: 0000-0002-2593-7196
Yazar: Emre SARANDÖL
Kurum: Department of Biochemistry, Uludağ University School of Medicine, Bursa, Turkey
Ülke: Turkey


Yayımlanma Tarihi : 4 Eylül 2019

EndNote %0 The European Research Journal The evaluation of the relationship between fetuin-A and traditional and non-traditional cardiovascular risk factors in kidney transplantation recipients %A Nizameddin Koca , Alparslan Ersoy , Barış Şensoy , Emine Kırhan , Sümeyye Güllülü , Melahat Di̇ri̇can , Emre Sarandöl %T The evaluation of the relationship between fetuin-A and traditional and non-traditional cardiovascular risk factors in kidney transplantation recipients %D 2019 %J The European Research Journal %P -2149-3189 %V 5 %N 5 %R doi: 10.18621/eurj.572606 %U 10.18621/eurj.572606