Abstract
Objective
Copper is an essential mineral nutrient for humans. Serum copper levels of hemodialysis patients are higher than those of healthy subjects, but it remains to be elucidated whether increased serum copper may have harmful effects. In addition, a recent in vitro study has shown that sevelamer can adsorb copper. In the present study, we searched for clinical factors associated with serum copper levels in hemodialysis patients.
Methods
This cross-sectional study included patients undergoing hemodialysis for more than 6 months. In these patients, we statistically tested associations between serum copper levels and other parameters, including nutritional markers, lipid profiles, oxidative stress, inflammation, and sevelamer administration.
Results
Among 48 patients (male/female = 28:20, age 71 ± 10 years, hemodialysis duration 84 ± 72 months), sevelamer hydrochloride was administered in 39 patients (81.3 %). In univariate analysis, serum copper levels showed significant positive correlations with serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde modified-LDL and negative correlations with plasma total homocysteine levels and the administered dose of sevelamer. In multivariate analysis, serum levels of LDL-cholesterol and hs-CRP were found to be independent determinants of serum copper levels.
Conclusion
We found that serum copper levels were independently associated with dyslipidemia and inflammation in hemodialysis patients, but the pathogenic roles of copper remain to be elucidated. In addition, potential effect of sevelamer on serum copper levels should be examined in appropriately designed studies.
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References
Tapiero H, Townsend DM, Tew KD (2003) Trace elements in human physiology and pathology. Copper. Biomed Pharmacother 57:386–398
Walter RM Jr, Uriu-Hare JY, Olin KL et al (1991) Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care 14:1050–1056
Bo S, Durazzo M, Gambino R et al (2008) Associations of dietary and serum copper with inflammation, oxidative stress, and metabolic variables in adults. J Nutr 138:305–310
Magalova T, Brtkova A, Bederova A, Kajaba I, Puchonova I (1994) Serum copper and zinc in industrial centers in Slovakia. Biol Trace Elem Res 40:225–235
Ferns GA, Lamb DJ, Taylor A (1997) The possible role of copper ions in atherogenesis: the Blue Janus. Atherosclerosis 133:139–152
Faraci FM, Didion SP (2004) Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 24:1367–1373
Shukla N, Maher J, Masters J, Angelini GD, Jeremy JY (2006) Does oxidative stress change ceruloplasmin from a protective to a vasculopathic factor? Atherosclerosis 187:238–250
Tonelli M, Wiebe N, Hemmelgarn B et al (2009) Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med 7:25
Takagi K, Masuda K, Yamazaki M et al (2010) Metal ion and vitamin adsorption profiles of phosphate binder ion-exchange resins. Clin Nephrol 73:30–35
Tsubakihara Y, Nishi S, Akiba T et al (2010) 2008 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease. Ther Apher Dial 14:240–275
Kalantar-Zadeh K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD (2003) Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis 42:761–773
Panichi V, Rosati A, Bigazzi R et al (2011) Anaemia and resistance to erythropoiesis-stimulating agents as prognostic factors in haemodialysis patients: results from the RISCAVID study. Nephrol Dial Transplant 26:2641–2648
Locsey L, Papp L (1983) Study of trace elements in patients on haemodialysis. Int Urol Nephrol 15:289–295
Healy H, Reith D, Morgan C, Clague A, Westhuyzen J (2000) Are metalloproteins and acute phase reactants associated with cardiovascular disease in end-stage renal failure? Ann Clin Lab Sci 30:295–304
Navarro-Alarcon M, Reyes-Perez A, Lopez-Garcia H, Palomares-Bayo M, Olalla-Herrera M, Lopez-Martinez MC (2006) Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical markers. Biol Trace Elem Res 113:209–222
Koca T, Berber A, Koca HB, Demir TA, Koken T (2010) Effects of hemodialysis period on levels of blood trace elements and oxidative stress. Clin Exp Nephrol 14:463–468
Veighey K, Booth J, Davenport A (2011) Does the choice of phosphate binder affect trace element levels in chronic kidney disease patients treated by regular haemodialysis? Nephrol Dial Transplant 26:1006–1010
Sondheimer JH, Mahajan SK, Rye DL et al (1988) Elevated plasma copper in chronic renal failure. Am J Clin Nutr 47:896–899
Ari E, Kaya Y, Demir H, Asicioglu E, Keskin S (2011) The correlation of serum trace elements and heavy metals with carotid artery atherosclerosis in maintenance hemodialysis patients. Biol Trace Elem Res 144:351–359
Higuchi T, Matsukawa Y, Okada K et al (2006) Correction of copper deficiency improves erythropoietin unresponsiveness in hemodialysis patients with anemia. Intern Med 45:271–273
Rounis E, Laing CM, Davenport A (2010) Acute neurological presentation due to copper deficiency in a hemodialysis patient following gastric bypass surgery. Clin Nephrol 74:389–392
Nishizawa Y, Shoji T, Kakiya R et al (2003) Non-high-density lipoprotein cholesterol (non-HDL-C) as a predictor of cardiovascular mortality in patients with end-stage renal disease. Kidney Int 63(Suppl 84):S117–S120
Shoji T, Masakane I, Watanabe Y, Iseki K, Tsubakihara Y, Committee of Renal Data Registry, Japanese Society for Dialysis Therapy (2011) Elevated non-high-density lipoprotein cholesterol (non-HDL-C) predicts atherosclerotic cardiovascular events in hemodialysis patients. Clin J Am Soc Nephrol 6:1112–1120
Uauy R, Olivares M, Gonzalez M (1998) Essentiality of copper in humans. Am J Clin Nutr 67(5 Suppl):952S–959S
Lin YF, Chien CT, Kan WC et al (2011) Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients: a randomized, open-label, parallel-group study. Clin Drug Investig 31:257–267
Chertow GM, Burke SK, Raggi P, Treat to Goal Working Group (2002) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62:245–252
Navarro-Gonzalez JF, Mora-Fernandez C, Muros de Fuentes M, Donate-Correa J, Cazana-Perez V, Garcia-Perez J (2011) Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients. Clin J Am Soc Nephrol 6:2272–2279
Ikee R, Tsunoda M, Sasaki N, Sato N, Hashimoto N (2012) Potential influence of sevelamer hydrochloride on responsiveness to erythropoiesis-stimulating agents in haemodialysis patients. Nephrology (Carlton) 17:225–229
Nakai S, Iseki K, Itami N et al (2012) Overview of regular dialysis treatment in Japan (as of 31 December 2009). Ther Apher Dial 16:11–53
Goto S, Fujii H, Kim JI, Fukagawa M (2010) Homocysteine and folic acid levels in hemodialysis patients treated with sevelamer hydrochloride. Clin Nephrol 73:420–425
Kirschbaum B (2000) Relationships between the copper and iron systems in hemodialysis patients and variables affecting these systems. Biol Trace Elem Res 77:13–24
Guo CH, Chen PC, Yeh MS, Hsiung DY, Wang CL (2011) Cu/Zn ratios are associated with nutritional status, oxidative stress, inflammation, and immune abnormalities in patients on peritoneal dialysis. Clin Biochem 44:275–280
Guo CH, Ko WS, Chen PC, Hsu GS, Lin CY, Wang CL (2009) Alterations in trace elements and oxidative stress in uremic patients with dementia. Biol Trace Elem Res 131:13–24
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Ikee, R., Tsunoda, M., Sasaki, N. et al. Clinical factors associated with serum copper levels and potential effect of sevelamer in hemodialysis patients. Int Urol Nephrol 45, 839–845 (2013). https://doi.org/10.1007/s11255-012-0211-3
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DOI: https://doi.org/10.1007/s11255-012-0211-3