Abstract
Vascular calcifications are recognized as important risk factors for uremia-induced cardiovascular disease. Yet some patients with chronic kidney disease (CKD) do not develop calcification despite exposure to the same uremic conditions. Physiological inhibitors of calcification such as fetuin A, which is an extraosseous calcification inhibitor, and osteoprotegerin (OPG), which is a regulator of bone resorption, may prevent the development and progression of vascular calcification. The aim of this work is to study the serum levels of fetuin A and OPG to understand their role in vascular calcification in patients with chronic renal impairment. A total of 80 subjects (60 CKD patients and 20 age- and sex-matched healthy controls) were studied. Fetuin A and osteoprotegerin were measured by ELISA; in addition to standard biochemical analysis, ECG and echocardiography were done to evaluate cardiovascular calcification. Fetuin A levels were significantly lower; OPG levels were significantly higher in the patients group compared to the controls. There was an inverse association between fetuin A and vascular calcifications in the patients group (P = −0.498, r = −0.001), while OPG showed a positive association (P = 0.510, r = 0.003). Serum fetuin A and osteoprotegerin levels were related to vascular calcification in CKD stages III, IV, and V. Decreased serum fetuin A may have a role in enhancing the cardiovascular morbidity and mortality in those patients by promoting a process of accelerated vascular calcification; elevated serum OPG levels increase with the progression of CKD, so these can be used as markers in the follow-up of those patients.
Similar content being viewed by others
References
Bargnoux AS, Dupuy AM, Garrigue V, Deleuze S, Cristol JP, Mourad G (2006) Renal transplantation decreases osteoprotegerin levels. Transplant Proc 38:2317–2318
Block GA, Spiegel DM, Ehrlich J et al (2005) Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 68:1815–1824
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342
Caglar K, Yilmaz MI, Saglam M, Cakir E, Kilic S, Sonmez A, Eyileten T, Yenicesu M, Oguz Y, Tasar M, Vural A, Ikizler TA, Stenvinkel P, Lindholm B (2008) Serum fetuin-A concentration and endothelial dysfunction in chronic kidney disease. Nephron Clin Pract 108:c233–c240. doi:10.1159/000120209
Coen G, Ballanti P, Balducci A, Calabria S, Fischer MS, Jankovic L, Manni M, Morosetti M, Moscaritolo E, Sardella D, Bonucci E (2002) Serum osteoprotegerin and renal osteodystrophy. Nephrol Dial Transplant 17:233–238
Cottone S, Palermo A, Arsena R, Riccobene R, Guarneri M, Mulè G et al (2010) Relationship of fetuin-A with glomerular filtration rate and endothelial dysfunction in moderate-severe chronic kidney disease. JNEPHROL 23(01):62–69
Cozzolino M, Biondi ML, Galassi A et al (2007) Gene polymorphisms and serum alpha-2-Heremans–Schmid levels in Italian haemodialysis patients. Am J Nephrol 27:639–642
El-Abbadi M, Giachelli CM (2007) Mechanisms of vascular calcification. Adv Chronic Kidney Dis 14:54–66
Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal failure. Am J Kidney Dis 32(Suppl 5):S112–S119
Grzegorzewska AE, Mlot M (2004) Serum osteoprotegerin level is lower in peritoneal dialysis patients than hemodialysis ones. Rocz Akad Med Bialymst 49:193–196
Jono S, Shioi A, Ikari Y, Nishizawa Y (2006) Vascular calcification in chronic kidney disease. J Bone Miner Metab 24:176–181
Kazama JJ, Shigematsu T, Yano K, Tsuda E, Miura M, Iwasaki Y et al (2002) Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure. Am J Kidney Dis 39:525–532
Ketteler M, Bongartz P, Westenfeld R (2003) Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 361:827–833
Ketteler M, Gross ML, Ritz E (2005) Calcification and cardiovascular problems in renal failure. Kidney Int 94(Suppl):S120–S127
Khamis T (2005) Epidemiology of chronic renal failure in Egypt. J Med Sci 5(7):825–829
Leung L (1993) Histidine-rich glycoprotein: an abundant plasma protein in search of a function. J Lab Clin Med 121:630–631
Moe SM, Chen NX (2004) Pathophysiology of vascular calcification in chronic kidney disease. Cir Res 95:560–567
Moe SM, Chen NX (2005) Inflammation and vascular calcification. Blood Purif 23:64–71
Morena M, Terrier N, Jaussent I, Leray-Moragues H, Chalabi L et al (2006) Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J Am Soc Nephrol 17:262–270
National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2suppl 1):S1–S266
Obrador GT, Ruthazer R, Arora P, Kausz AT, Pereira BJ (2005) Prevalence of and factors associated with suboptimal care before initiation of dialysis in the United States. J Am Soc Nephrol 10:1793–1800
Price PA, Lim JE (2003) The inhibition of calcium phosphate precipitation by fetuin is accompanied by the formation of a fetuin–mineral complex. J Biol Chem 278:22144–22152
Price PA, June HH, Buckley JR (2001) Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 21:1610–1616
Sarnak MJ, Levey AS (2000) Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis 35(4 suppl 1):S117–S131
Sato T, Tominaga Y, Iwasaki Y, Kazama JJ, Shigematsu T, Inagaki H et al (2001) Osteoprotegerin levels before and after renal transplantation. Am J Kidney Dis 38(Suppl 1):S175–S177
Schafer C, Heiss A, Schwarz A (2003) The serum protein alpha 2-Heremans–Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 112:357–366
Shroff RC, Shah V, Hiorns MP et al (2008) The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis. Nephrol Dial Transplant 23:3263–3271
Tonelli M, Pfeffer MA (2007) Kidney disease and cardiovascular risk. Annu Rev Med 58:123–139
Vattikuti R, Towler DA (2004) Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol Endocrinol Metab 286:E686–E696
Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, Liu SF, Li PK, Sanderson JE (2005) Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 20:1676–1685
Westenfeld R, Jahnen-Dechent W, Ketteler M (2007) Vascular calcification and fetuin-A deficiency in chronic kidney disease. Trends Cardiovasc Med 17:124–128
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nessim, I.G., el Wahab, A.A., Madani, H.A. et al. Evaluation of serum osteoprotegerin and fetuin A levels in Egyptian patients with chronic kidney disease. Comp Clin Pathol 20, 421–425 (2011). https://doi.org/10.1007/s00580-011-1281-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00580-011-1281-9