Skip to main content

Advertisement

SpringerLink
Log in

Serum Zn Levels and Cu/Zn Ratios Worsen in Hemodialysis Patients, Implying Increased Cardiovascular Risk: A 2-Year Longitudinal Study

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The objective of this study was to analyze serum Zn and Cu concentrations and Cu/Zn ratios in 116 hemodialysis patients (HPs) over a 2-year longitudinal study at four time points (6-month intervals). The relation exerted on these values by 26 biochemical and nutritional indexes, the age and drug consumption of the patients, and the etiology of their disease were also evaluated. A healthy control group (n = 50) was also studied. Mean serum Zn concentrations were lower (p = 0.009) and the Cu/Zn ratios higher (p = 0.009) in HPs than in controls. Serum Cu levels in HP did not differ to those of controls. At all four sampling times, the mean serum Zn levels and Cu/Zn ratios were lower and higher, respectively, in HPs than in the controls. There was a significant reduction in serum Zn levels and an increase in Cu concentrations and Cu/Zn ratios in HPs from the second to the fourth sampling. Serum Zn levels of the HPs diminish with age older than 50 years. Serum Cu levels were significantly higher in patients consuming antihypercalcemic or anti-infarction drugs, whereas serum Cu levels and Cu/Zn ratios were significantly lower in those treated with diuretics. Diminished Zn levels were negatively correlated with low-density lipoprotein (LDL) cholesterol in HPs; however, enhanced Cu/Zn ratios were positively correlated with total cholesterol and LDL cholesterol. Both findings indicate an increased cardiovascular risk. We conclude that this study contributes the first evidence of a correlation between marked dyslipidemia and worsened Cu/Zn ratios in HPs, implying an increased risk of diseases associated with elevated oxidative stress, inflammation, and depressed immune function, such as cardiovascular diseases.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tomic S, Brkic S, Maric D, Mikic AN (2008) Lipid and protein oxidation in female patients with chronic fatigue syndrome. Arch Med Sci 8:886–891

    Google Scholar 

  2. Himmelfarb J (2008) Oxidative stress in hemodialysis. Contrib Nephrol 161:132–137

    Article  PubMed  Google Scholar 

  3. Crisponi G, Nurchi VM, Fanni D, Gerosa C, Nemolato S, Faa G (2010) Copper-related diseases: from chemistry to molecular pathology. Coord Chem Rev 254:876–889

    Article  CAS  Google Scholar 

  4. Nihi MM, Manfro RC, Martins C, Suliman M, Murayama Y, Riella MC (2010) Association between body fat, inflammation and oxidative stress in hemodialysis. J Bras Nefrol 32:9–15

    Article  PubMed  Google Scholar 

  5. Koc-Zorawska E, Malyszko J, Zbroch E, Malyszko J, Mysliwiec M (2012) Vascular adhesion protein-1 and renalase in regard to diabetes in hemodialysis patients. Arch Med Sci 8:1048–1052

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Gilmour ER, Hartley GH, Goodship THJ (1998) Trace elements and vitamins in renal disease. In: Mitch WE, Klahr S (eds) Handbook of nutrition and the kidney, 3rd edn. Lippincott-Raven, Philadelphia, pp 107–122

    Google Scholar 

  7. Gentil MG, Maná GM, D’Amico G, Testolin G, Porrini M, Simonetti P (1988) Vitamina nutrición en pacientes con insuficiencia renal crónica y la manipulación de la dieta. Contrib Nephrol 65:43–50

    Google Scholar 

  8. Guo C-H, Wang C-L (2013) Research paper effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients. Int J Med Sci 10:79–89

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Rashidi AA, Salehi M, Piroozmand A, Sagheb MM (2009) Effects of zinc supplementation on serum zinc and C-reactive protein concentrations in hemodialysis patients. J Ren Nutr 19:475–478

    Article  CAS  PubMed  Google Scholar 

  10. Bozalioglu S, Ozkan Y, Turan M, Simsek B (2005) Prevalence of zinc deficiency and immune response in short-term hemodialysis. J Trace Elem Med Biol 18:243–249

    Article  CAS  PubMed  Google Scholar 

  11. Kasama RK (2010) Trace minerals in patients with end-stage renal disease. Semin Dialysis 23:561–570

    Article  Google Scholar 

  12. Navarro-Alarcón M, Reyes-Pérez A, López-García H, Palomares-Bayo M, Olalla-Herrera M, López-Martínez 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  Google Scholar 

  13. Sahin H, Uyanik F, Inanc N, Erdem O (2009) Serum zinc, plasma ghrelin, leptin levels, selected biochemical parameters and nutritional status in malnourished hemodialysis patients. Biol Trace Elem Res 127:191–199

    Article  CAS  PubMed  Google Scholar 

  14. Tonelli M, Wiebe N, Hemmelgarn B, Klarenbach S, Field C, Manns B, Thadhani R, Gill J (2009) Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med 7:25

    Article  PubMed Central  PubMed  Google Scholar 

  15. Ikee R, Tsunoda M, Sasaki N, Sato N, Hashimoto N (2013) Clinical factors associated with serum copper levels and potential effect of sevelamer in hemodialysis patients. Int Urol Nephrol 45:839–845

    Article  CAS  PubMed  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. Guo C-H, Chen P-C, Yeh M-S, Hsiung D-Y, Wang C-L (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  CAS  PubMed  Google Scholar 

  18. Kang YJ (2011) Copper and homocysteine in cardiovascular diseases. Pharmacol Ther 129:321–331

    Article  CAS  PubMed  Google Scholar 

  19. Karahan SC, Deger O, Orem A, Ucar F, Erem C, Alver A (2001) The effects of impaired trace element status on polymorphonuclear leukocyte activation in the development of vascular complications in type 2 diabetes mellitus. Clin Chem Lab Med 39:109–115

    Article  CAS  PubMed  Google Scholar 

  20. Barrera R, Schattner M, Gabovich N, Zhang J, Saeed M, Genao A (2003) Bacteremic episodes and copper/zinc ratio in patients receiving home parenteral nutrition. Nutr Clin Pract 18:529–532

    Article  CAS  PubMed  Google Scholar 

  21. Martí del Moral L, Agil A, Navarro-Alarcón M, López-Gª de la Serrana H, Palomares-Bayo M, Oliveras-López MJ (2011) Altered serum selenium and uric acid levels and dyslipidemia in hemodialysis patients could be associated with an enhanced cardiovascular risk. Biol Trace Elem Res 144:496–503

    Article  PubMed  Google Scholar 

  22. Navarro M, Wood R (2003) Plasma changes in micronutrients following a multivitamin and mineral supplement in healthy humans. J Am Coll Nutr 22:24–132

    Article  Google Scholar 

  23. 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  CAS  PubMed  Google Scholar 

  24. Aranha LN, Lobo JC, Stockler-Pinto MB, Leal VO, Machado JP, Mafra D (2012) Relationship between zinc levels and plasma leptin in hemodialysis patients. J Trace Elem Med Biol 26:238–242

    Article  CAS  PubMed  Google Scholar 

  25. Ribeiro RC, Sales VS, Neves FA, Draibe S, Brandao-Neto J (2004) Effects of zinc on cell-mediated immunity in chronic hemodialysis patients. Biol Trace Elem Res 98:209–217

    Article  CAS  PubMed  Google Scholar 

  26. Huang JW, Hung KY, Lee SH (2000) Trace elements in blood and dialysate among continuous ambulatory peritoneal dialysis patients: a prospective, multicenter collaborative study. Dial Transplant 29:62–68

    Google Scholar 

  27. Dogan A, Dip A, Söylemezoglu (2008) Effects of hemodialysisi on blood lead, cadmium, zinc and copper levels in chronic renal failure patients. Toxicol Lett 180S:S202

    Article  Google Scholar 

  28. Batista MN, Cuparri L, Campos Pedrosa LF, Almeida MG, Almeida JB, Quieroz de Medeiros AC, Canziani MEF (2006) Effect of end-stage renal disease and diabetes on zinc and copper status. Biol Trace Elem Res 112:1–11

    Article  CAS  PubMed  Google Scholar 

  29. Berger MM, Shenkin A, Revelly JP, Roberts E, Cayeux MC, Baines M, Chiolero RL (2004) Copper, selenium, zinc and thiamine balances during continuous venovenous hemodiafiltration inc critically ill patients. Am J Clin Nutr 80:410–416

    CAS  PubMed  Google Scholar 

  30. Takeda T, Yukioka T, Shimazaki S (2000) Cupric sulfate intoxication with rhabdomyolysis, treated with chelating agents and blood purification. Intern Med 39:253–255

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition and Food Chemistry, School of Pharmacy, University of Granada, 18071, Granada, Spain

    Maria Luisa Reina de la Torre, Miguel Navarro-Alarcón, Loreto Martí del Moral, Herminia López-Gª de la Serrana, María Jesús Oliveras López & Rosa María Blanca Herrera

  2. Hemodialysis Service, Guadix Hospital, Granada, Spain

    Magdalena Palomares-Bayo

  3. Department of Pharmacology, School of Medicine, University of Granada, 18071, Granada, Spain

    Ahmad Agil

Authors
  1. Maria Luisa Reina de la Torre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miguel Navarro-Alarcón
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Loreto Martí del Moral
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Herminia López-Gª de la Serrana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Magdalena Palomares-Bayo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María Jesús Oliveras López
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rosa María Blanca Herrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ahmad Agil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miguel Navarro-Alarcón.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reina de la Torre, M.L., Navarro-Alarcón, M., del Moral, L.M. et al. Serum Zn Levels and Cu/Zn Ratios Worsen in Hemodialysis Patients, Implying Increased Cardiovascular Risk: A 2-Year Longitudinal Study. Biol Trace Elem Res 158, 129–135 (2014). https://doi.org/10.1007/s12011-014-9921-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-9921-y

Keywords

Search

Navigation