Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Nutrition in acute and chronic diseases

Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: Cross-sectional data from the NHANES 2011–2016

Abstract

Background & objective

Chronic kidney disease (CKD) is a common condition in worldwide with underlying causes. The role of trace elements such as copper and zinc in CKD is uncertain. We aimed to examine the relationship of serum copper and zinc with kidney function status and explore its possible effect modifiers in the general population.

Methods

Data from 5353 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed for the role of trace elements in the age range 18 to 80 years. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and increased urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g.

Results

Findings showed a significant positive association between serum copper and urinary ACR (OR = 1.04, 95% CI = 1.00–1.07). Serum copper levels of 18.0 μmol/L (median) or higher (reference level <18.0 μmol/L) were significantly associated with increased urinary ACR (OR = 1.67, 95% CI = 1.21–2.31) after adjusting for confounding factors. In contrast, there was a significant inverse association between serum zinc and reduced eGFR (OR = 0.89,95% CI = 0.81–0.99). Where serum zinc level was greater than 12.3 μmol/L (median), the prevalence of reduced eGFR was lower (OR = 0.65, 95% CI = 0.16–0.60). In addition, a stratified analysis based on various risk factors found that in those individuals with serum albumin greater than 43 g/L or systolic blood pressure greater than 120 mmHg, positive correlations between serum copper and risk of increased urinary ACR was more significant.

Conclusions

Our findings suggest that the reference levels of serum copper and zinc levels in healthy individuals may be different from current understanding. If further studies substantiate the same, the results will be a useful guide for designing future clinical trials and nutritional guidelines.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Multivariate adjusted association between serum zinc and copper concentrations and kidney function status*.
Fig. 2: Stratified analysis for the kidney outcomes and trace elements in various subgroups*.

Data availability

The datasets analysed during the current study are available in the National Health and Nutrition Examination Survey repository, [https://wwwn.cdc.gov/nchs/nhanes].

References

  1. Mills KT, Xu Y, Zhang W, Bundy JD, Chen CS, Kelly TN, et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int. 2015;88:950–7.

    Article  Google Scholar 

  2. Stevens PE, Levin A. Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158:825–30.

    Article  Google Scholar 

  3. Huan L, Yuezhong L, Chao W, HaiTao T. The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China. Clinics. 2016;71:243–50.

    Article  Google Scholar 

  4. Liu S, Niu J, Wu S, Xin Z, Zhao Z, Xu M, et al. Urinary albumin-to-creatinine ratio levels are associated with subclinical atherosclerosis and predict CVD events and all-cause deaths: A prospective analysis. BMJ Open. 2021;11:e40890.

    Google Scholar 

  5. Chang DR, Yeh HC, Ting IW, Lin CY, Huang HC, Chiang HY, et al. The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality. Sci Rep. 2021;11:7851.

    CAS  Article  Google Scholar 

  6. Strain JJ. Newer aspects of micronutrients in chronic disease: Copper. Proc Nutr Soc. 1994;53:583–98.

    CAS  Article  Google Scholar 

  7. Linder MC, Hazegh-Azam. M. Copper biochemistry and molecular biology. Am J Clin Nutr. 1996;63:797S–811S.

    CAS  PubMed  Google Scholar 

  8. Chen A, Li G, Liu. Y. Association between copper levels and myocardial infarction: A meta-analysis. Inhal Toxicol. 2015;27:237–46.

    CAS  Article  Google Scholar 

  9. Ebara M, Fukuda H, Hatano R, Saisho H, Nagato Y, Suzuki K, et al. Relationship between copper, zinc, and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma. J Hepatol. 2000;33:415–22.

    CAS  Article  Google Scholar 

  10. Grammer TB, Kleber ME, Silbernagel G, Pilz S, Scharnagl H, Lerchbaum E, et al. Copper, ceruloplasmin, and long-term cardiovascular and total mortality (the Ludwigshafen Risk and Cardiovascular Health Study). Free Radic Res. 2014;48:706–15.

    CAS  Article  Google Scholar 

  11. King JC. Zinc: An essential but elusive nutrient. Am J Clin Nutr. 2011;94:679S–84S.

    Article  Google Scholar 

  12. Prasad AS. Zinc: An antioxidant and anti-inflammatory agent: Role of zinc in degenerative disorders of aging. J Trace Elem Med Biol. 2014;28:364–71.

    CAS  Article  Google Scholar 

  13. Roney N, Osier M, Paikoff SJ, Smith CV, Williams M, De Rosa. CT. ATSDR evaluation of the health effects of zinc and relevance to public health. Toxicol Ind Health. 2006;22:423–93.

    CAS  Article  Google Scholar 

  14. Tsuboi A, Terazawa WM, Kazumi T, Fukuo K. Serum copper, zinc and risk factors for cardiovascular disease in community-living Japanese elderly women. Asia Pac J Clin Nutr. 2014;23:239–45.

    CAS  PubMed  Google Scholar 

  15. Freitas EP, Cunha AT, Aquino SL, Pedrosa LF, Lima SC, Lima JG, et al. Zinc status biomarkers and cardiometabolic risk factors in metabolic syndrome: A case-control study. Nutrients. 2017;9:175.

  16. Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. https://www.cdc.gov/nchs/nhanes/index.htm.

  17. Kobayashi K, Katsuya Y, Abdulah R, Koyama. H. Rapid and direct determination of selenium, copper, and zinc in blood plasma by flow injection-inductively coupled plasma-mass spectrometry. Biol Trace Elem Res. 2007;115:87–93.

    CAS  Article  Google Scholar 

  18. National Health and Nutrition Examination Survey 2011-2012 Data Documentation, Codebook, and Frequencies. Copper, Selenium & Zinc - Serum (CUSEZN_G). https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/CUSEZN_G.htm.

  19. National Health and Nutrition Examination Survey 2013-2014 Data Documentation, Codebook, and Frequencies. Copper, Selenium & Zinc - Serum (CUSEZN_H). https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/CUSEZN_H.htm.

  20. National Health and Nutrition Examination Survey. NHANES 2011-2012 Laboratory Methods. https://wwwn.cdc.gov/nchs/data/nhanes/2011-2012/labmethods/CUSEZN_G_met_serum_elements.pdf.

  21. National Health and Nutrition Examination Survey. 2017_MEC_Laboratory_Procedures_Manual. https://wwwn.cdc.gov/nchs/data/nhanes/2015-2016/manuals/2016_MEC_Laboratory_Procedures_Manual.pdf.

  22. National Health and Nutrition Examination Survey 2015-2016 Data Documentation, Codebook, and Frequencies. Copper, Selenium & Zinc - Serum (CUSEZN_I). https://wwwn.cdc.gov/Nchs/Nhanes/2015-2016/CUSEZN_I.htm.

  23. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AR, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.

    Article  Google Scholar 

  24. Shen Y, Yin Z, Lv Y, Luo J, Shi W, Fang J, et al. Plasma element levels and risk of chronic kidney disease in elderly populations (≥90 Years old). Chemosphere 2020;254:126809.

    CAS  Article  Google Scholar 

  25. Makhlough A, Makhlough M, Shokrzadeh M, Mohammadian M, Sedighi O, Faghihan M. Comparing the levels of trace elements in patients with diabetic nephropathy and healthy individuals. Nephrourol Mon. 2015;7:e28576.

    Article  Google Scholar 

  26. Liu X, Zhao Y, Feng. Y. Estimation of 24-h urine protein excretion using urine albumin-to-creatinine ratio from an in-hospital population. Med Sci Monit. 2022;28:e934307.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Yang F, Yi X, Guo J, Xu S, Xiao Y, Huang X, et al. Association of plasma and urine metals levels with kidney function: A population-based cross-sectional study in China. Chemosphere 2019;226:321–8.

    CAS  Article  Google Scholar 

  28. Brewer GJ. Risks of copper and iron toxicity during aging in humans. Chem Res Toxicol. 2010;23:319–26.

    CAS  Article  Google Scholar 

  29. de Romana DL, Olivares M, Uauy R, Araya. M. Risks and benefits of copper in light of new insights of copper homeostasis. J Trace Elem Med Biol. 2011;25:3–13.

    Article  Google Scholar 

  30. Gaetke LM, Chow-Johnson HS, Chow. CK. Copper: Toxicological relevance and mechanisms. Arch Toxicol. 2014;88:1929–38.

    CAS  Article  Google Scholar 

  31. Gaetke LM, Chow CK. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 2003;189:147–63.

    CAS  Article  Google Scholar 

  32. Pereira TC, Campos MM, Bogo. MR. Copper toxicology, oxidative stress, and inflammation using zebrafish as experimental model. J Appl Toxicol. 2016;36:876–85.

    CAS  Article  Google Scholar 

  33. Uriu-Adams JY, Keen. CL. Copper, oxidative stress, and human health. Mol Asp Med. 2005;26:268–98.

    CAS  Article  Google Scholar 

  34. Baltaci AK, Yuce K, Mogulkoc. R. Zinc metabolism and metallothioneins. Biol Trace Elem Res. 2018;183:22–31.

    CAS  Article  Google Scholar 

  35. Hambidge M, Krebs. NF. Zinc metabolism and requirements. Food Nutr Bull. 2001;22:126–32.

    Article  Google Scholar 

  36. Wastney ME, House WA, Barnes RM, Subramanian KN. Kinetics of zinc metabolism: Variation with diet, genetics and disease. J Nutr. 2000;130(5S Suppl):1355S–9S.

    CAS  Article  Google Scholar 

  37. Mocchegiani E, Giacconi R, Muzzioli M, Cipriano. C. Zinc, infections and immunosenescence. Mech Ageing Dev. 2000;121:21–35.

    CAS  Article  Google Scholar 

  38. Mocchegiani E, Muzzioli M, Giacconi. R. Zinc and immunoresistance to infection in aging: New biological tools. Trends Pharm Sci. 2000;21:205–08.

    CAS  Article  Google Scholar 

  39. Maruyama Y, Nakashima A, Fukui A, Yokoo. T. Zinc deficiency: Its prevalence and relationship to renal function in Japan. Clin Exp Nephrol 2021;25:771–8.

    CAS  Article  Google Scholar 

  40. Ye M, Li G, Yan P, Ren J, Zheng L, Han D, et al. Removal of metals from lead-zinc mine tailings using bioleaching and followed by sulfide precipitation. Chemosphere 2017;185:1189–96.

    CAS  Article  Google Scholar 

  41. Lezaic V, Ristic S, Dopsaj V, Marinkovic. J. Is morning urinary protein-to-creatinine ratio a reliable estimator of 24-hour proteinuria in patients with kidney diseases? SRP Arh Celok Lek. 2010;138:726–31.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the investigators and participants of the National Health and Nutrition Examination Survey, which made this report possible.

Funding

This work was supported by High Level-Hospital Program, Health Commission of Guangdong Province, China (HKUSZH20192026).

Author information

Authors and Affiliations

Authors

Contributions

CJ and GW designed the research; CJ analyzed the data; CJ and HY wrote the paper. All authors contributed to data collection and reviewed/edited the manuscript for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gang Wang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jiang, C., Ye, H., Cui, L. et al. Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: Cross-sectional data from the NHANES 2011–2016. Eur J Clin Nutr (2022). https://doi.org/10.1038/s41430-022-01181-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41430-022-01181-8

Search

Quick links