Skip to main content
Log in

Clinical factors associated with serum copper levels and potential effect of sevelamer in hemodialysis patients

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Tapiero H, Townsend DM, Tew KD (2003) Trace elements in human physiology and pathology. Copper. Biomed Pharmacother 57:386–398

    Article  PubMed  CAS  Google Scholar 

  2. 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

    Article  PubMed  Google Scholar 

  3. 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

    PubMed  CAS  Google Scholar 

  4. 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

    Article  PubMed  CAS  Google Scholar 

  5. Ferns GA, Lamb DJ, Taylor A (1997) The possible role of copper ions in atherogenesis: the Blue Janus. Atherosclerosis 133:139–152

    Article  PubMed  CAS  Google Scholar 

  6. Faraci FM, Didion SP (2004) Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 24:1367–1373

    Article  PubMed  CAS  Google Scholar 

  7. 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

    Article  PubMed  CAS  Google Scholar 

  8. Tonelli M, Wiebe N, Hemmelgarn B et al (2009) Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med 7:25

    Article  PubMed  Google Scholar 

  9. 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

    PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. 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

    Article  PubMed  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. Locsey L, Papp L (1983) Study of trace elements in patients on haemodialysis. Int Urol Nephrol 15:289–295

    Article  PubMed  CAS  Google Scholar 

  14. 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

    PubMed  CAS  Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. Sondheimer JH, Mahajan SK, Rye DL et al (1988) Elevated plasma copper in chronic renal failure. Am J Clin Nutr 47:896–899

    PubMed  CAS  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  PubMed  Google Scholar 

  21. 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

    PubMed  CAS  Google Scholar 

  22. 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

    Article  Google Scholar 

  23. 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

    Article  PubMed  CAS  Google Scholar 

  24. Uauy R, Olivares M, Gonzalez M (1998) Essentiality of copper in humans. Am J Clin Nutr 67(5 Suppl):952S–959S

    PubMed  CAS  Google Scholar 

  25. 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

    Article  PubMed  Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. 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

    Article  PubMed  CAS  Google Scholar 

  28. 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

    Article  CAS  Google Scholar 

  29. 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

    Article  PubMed  Google Scholar 

  30. 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

    PubMed  CAS  Google Scholar 

  31. 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

    Article  PubMed  CAS  Google Scholar 

  32. 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

    Article  PubMed  CAS  Google Scholar 

  33. 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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ryota Ikee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-012-0211-3

Keywords

Navigation