Summary
OBJECTIVES: Fetuin A, a circulating inhibitor of calcification, is regulated as a negative acute-phase protein. However, its relationship with outcomes of patients undergoing hemodialysis has not been well evaluated. The aim of our study was to determine the association between fetuin-A and some factors of metabolism and their impact on all-cause mortality in hemodialysis patients. PATIENTS AND METHODS: The study comprised 106 hemodialysis patients, 45 of whom were women. Levels of serum fetuin-A were measured by ELISA and serum intact parathyroid hormone (iPTH) by immunoassay in each patient. Serum Ca, serum P, Ca × P product, alkaline phosphatase, cholesterol, triglycerides, bicarbonate, albumin, homocysteine and C-reactive protein (CRP) were measured using routine laboratory methods. Survival rates were analyzed using Kaplan–Meier survival curves. A Cox regression model was used to access the possible influence of variables on all-cause mortality. RESULTS: The mean value of fetuin-A was 15.3 ± 3.8 g/l, range 5.5–23.7 g/l. Significant correlations were found between serum fetuin-A and serum iPTH (r = –0.239; P = 0.014), alkaline phosphatase (r = –0.240; P = 0.013), triglycerides (r = +0.236; P = 0.015) and serum albumin level (r = +0.286; P = 0.003). Patients were followed-up prospectively from the first day of the laboratory measurement for a maximum of 752 days or until death. A total of 24 patients died. Surviving patients had higher levels of fetuin-A (P = 0.005), serum cholesterol (P = 0.0001), triglycerides (P = 0.004), albumin (P = 0.0001) and homocysteine (P = 0.028). Kaplan–Meier survival analysis showed higher mortality in the first tertile of fetuin-A than in the third tertile (P = 0.0297). In our patients, serum Ca (P = 0.025), serum P (P = 0.040) and the Ca × P product (P = 0.039) were found to be predictors of mortality in the Cox multivariable regression model. CONCLUSIONS: In patients undergoing hemodialysis, lower fetuin-A levels are associated with higher mortality. Metabolism of Ca and P were directly associated with higher mortality.
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References
Unger F (2008) Health is Wealth – toward a European lead market in health care. Acta Medico-Biotechnica 1: 11–8
Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, et al (2005) Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 20: 1676–85
La Clair R, O'Neal K, Ofner S, Sosa MJ, Labarrere CA, et al (2008) Precision of biomarkers to define chronic inflammation in CKD. Am J Nephrol 28: 808–12
London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18: 1731–40
Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM (2001) Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 38: 938–42
Ketteler M (2005) Fetuin-A and extraosseous calcification in uremia. Curr Opin Nephrol Hypertens 14: 337–42
Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Boem R, et al (2003) Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 361: 827–33
Cozzolino M, Mazzaferro S, Pugliese F, Brancaccio D (2008) Vascular calcification and uremia: what do we know? Am J Nephrol 28: 339–46
Pupim LB, Himmelfarb J, McMonagle E, Shyr Y, Ikizler TA (2004) Influence of initiation of maintenance hemodialysis on biomarkers of inflammation and oxidative stress. Kidney Int 65: 2371–9
Honda H, Quereshi AR, Heimbuerger O, Barany P, Wang K, Pecoits-Filho R, et al (2006) Serum albumin, C-reactive protein, interleukin-6, and fetuin A as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 47: 139–48
Stenvinkel P, Wang K, Quereshi AR, Axelsson J, Pecoits-Filho R, Gao P, et al (2005) Low fetuin-A levels are associated with cardiovascular death: impact of variations in the gene encoding fetuin. Kidney Int 67: 2383–92
El-Abbadi M, Giachelli CM (2005) Arteriosclerosis, calcium phosphate deposition and cardiovascular disease in uremia: current concepts at the bench. Curr Opin Nephrol Hypertens 14: 519–24
Mehrotra R, Westenfeld R, Christenson P, Budoff M, Ipp E, Takasu J, et al (2005) Serum fetuin-A in nondialyzed patients with diabetic nephropathy: relationship with coronary artery calcification. Kidney Int 67: 1070–7
Moe MS, Reslerova M, Ketteler M, O'Neill K, Duan D, Koczman J (2005) Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease. Kidney Int 67: 2295–304
Cooper BA, Penne EL, Bartlett LH, Pollock CA (2004) Protein malnutrition and hypoalbuminemia as predictors of vascular events and mortality in ESRD. Am J Kidney Dis 43: 61–6
Reynolds JL, Skepper JN, McNair R, Kasama T, Gupta K, Weissberg PL, et al (2005) Multifunctional roles for serum protein fetuin-A in inhibition of vascular smooth muscle cell calcification. J Am Soc Nephrol 16: 2920–30
Kalpakian MA, Mehrotra R (2007) Vascular calcification and disordered mineral metabolism in dialysis patients. Semin Dial 20: 139–43
Mehrotra R (2007) Emerging role for fetuin-A as contributor to morbidity and mortality in chronic kidney disease. Kidney Int 72: 137–40
Hermans MMH, Brandenburg V, Ketteler M, Kooman JP, Van der Sande FM, Boeschoten EW (2007) Association of serum fetuin-A levels with mortality in dialysis patients. Kidney Int 72: 202–7
Papagianni A (2008) Serum fetuin-A levels, aortic calcification and mortality in chronic haemodialysis patients. NDT Plus 1: 341
Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK (2001) Association of elevated serum PO4, Ca × PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12: 2131–8
Marco MP, Craver L, Betriu A, Belart M, Fibla J, Fernandez E (2003) Higher impact of mineral metabolism on cardiovascular mortality in a European hemodialysis population. Kidney Int 63[Suppl 85]: 111–4
Noordzij M, Korevaar JC, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT (2005) The kidney disease outcomes quality initiative (K/DOQI) guideline for bone metabolism and disease in CKD: association with mortality in dialysis patients. Am J Kidney Dis 46: 925–32
Block GA, Klassen PS, Lazarus MJ, Ofsthun N, Lowrie EG, Chertow GM (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15: 2208–18
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Balon, B., Knehtl, M., Bevc, S. et al. Fetuin-A as a risk factor for mortality in hemodialysis patients. Wien Klin Wochenschr 122 (Suppl 2), 63–67 (2010). https://doi.org/10.1007/s00508-010-1348-7
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DOI: https://doi.org/10.1007/s00508-010-1348-7