Skip to main content
SpringerLink
Log in

Associations of Blood Heavy Metals with Uric Acid in the Korean General Population: Analysis of Data from the 2016–2017 Korean National Health and Nutrition Examination Survey

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

Abstract

We hypothesized that blood heavy metal levels such as lead, cadmium, and mercury were associated with uric acid level and hyperuricemia, and that this association remains significant after adjustment for other metals. We tested this hypothesis using the Korean National Health and Nutrition Examination Survey data. Beta coefficients and 95% confidence intervals (95% CIs) were calculated using multiple linear regression, and odds ratios (ORs) and 95% CIs were calculated using logistic regression in the cross-sectional study design. Relative to women, men had a higher geometric mean (GM) of lead (1.95 vs. 1.50 μg/dL) and mercury (3.94 vs. 2.77 μg/L), a lower GM of cadmium (0.80 vs. 1.04 μg/L), and a higher arithmetic mean (AM) of uric acid (5.84 vs. 4.40 mg/dL). Women had significant positive associations of log uric acid level with doubling of lead and mercury, and negative association with cadmium. Logistic regression analysis indicated the inverse association of serum hyperuricemia with doubling of blood metals was only significant for cadmium in women (OR = 0.641, 95% CI = 0.463 to 0.886) and the associations of serum hyperuricemia in the highest versus lowest quartiles of heavy metals were only significant for cadmium in women (OR = 0.495, 95% CI = 0.246 to 0.998). For both genders, age and estimated glomerular filtration rate (e-GFR) had negative associations with uric acid, but hypertension and triglycerides had positive associations with uric acid. In conclusion, blood lead and mercury levels were positively associated with uric acid level, but blood cadmium level was inversely associated with uric acid level and hyperuricemia in women.

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

Similar content being viewed by others

Data Availability

Available

References

  1. Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41(6):1183–1190

    CAS  Google Scholar 

  2. Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V (2016) Regulation of uric acid metabolism and excretion. Int J Cardiol 213:8–14

    PubMed  Google Scholar 

  3. Borghi C (2017) The management of hyperuricemia: back to the pathophysiology of uric acid. Curr Med Res Opin 33(sup3):1–4

    PubMed  Google Scholar 

  4. So A, Thorens B (2010) Uric acid transport and disease. J Clin Invest 120(6):1791–1799

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Dehghan A, van Hoek M, Sijbrands EJ, Hofman A, Witteman JC (2008) High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care 31(2):361–362

    CAS  PubMed  Google Scholar 

  6. El Ridi R, Tallima H (2017) Physiological functions and pathogenic potential of uric acid: a review. J Adv Res 8(5):487–493

    PubMed  PubMed Central  Google Scholar 

  7. Onat A, Uyarel H, Hergenc G, Karabulut A, Albayrak S, Sari I, Yazici M, Keles I (2006) Serum uric acid is a determinant of metabolic syndrome in a population-based study. Am J Hypertens 19(10):1055–1062

    CAS  PubMed  Google Scholar 

  8. Madero M, Sarnak MJ, Wang X, Greene T, Beck GJ, Kusek JW, Collins AJ, Levey AS, Menon V (2009) Uric acid and long-term outcomes in CKD. Am J Kidney Dis 53(5):796–803

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kanbay M, Segal M, Afsar B, Kang D-H, Rodriguez-Iturbe B, Johnson RJ (2013) The role of uric acid in the pathogenesis of human cardiovascular disease. Heart 99(11):759–766

    CAS  PubMed  Google Scholar 

  10. Baker JF, Krishnan E, Chen L, Schumacher HR (2005) Serum uric acid and cardiovascular disease: recent developments, and where do they leave us? Am J Med 118(8):816–826

    CAS  PubMed  Google Scholar 

  11. Fang J, Alderman MH (2000) Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Health and Nutrition Examination Survey. JAMA 283(18):2404–2410

  12. Ioachimescu AG, Brennan DM, Hoar BM, Hazen SL, Hoogwerf BJ (2008) Serum uric acid is an independent predictor of all-cause mortality in patients at high risk of cardiovascular disease: a preventive cardiology information system (PreCIS) database cohort study. Arthritis Rheum 58(2):623–630

    CAS  PubMed  Google Scholar 

  13. Ekong EB, Jaar BG, Weaver VM (2006) Lead-related nephrotoxicity: a review of the epidemiologic evidence. Kidney Int 70(12):2074–2084

    CAS  PubMed  Google Scholar 

  14. Khalil-Manesh F, Gonick HC, Cohen AH, Alinovi R, Bergamaschi E, Mutti A, Rosen VJ (1992) Experimental model of lead nephropathy. I Continuous high-dose lead administration. Kidney Int 41(5):1192–1203

    CAS  PubMed  Google Scholar 

  15. Akesson A, Lundh T, Vahter M, Bjellerup P, Lidfeldt J, Nerbrand C, Samsioe G, Stromberg U, Skerfving S (2005) Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect 113(11):1627–1631

    PubMed  PubMed Central  Google Scholar 

  16. Tsaih SW, Korrick S, Schwartz J, Amarasiriwardena C, Aro A, Sparrow D, Hu H (2004) Lead, diabetes, hypertension, and renal function: the normative aging study. Environ Health Perspect 112(11):1178–1182

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Fadrowski JJ, Navas-Acien A, Tellez-Plaza M, Guallar E, Weaver VM, Furth SL (2010) Blood lead level and kidney function in US adolescents: the third National Health and Nutrition Examination Survey. Arch Intern Med 170(1):75–82

    CAS  PubMed  Google Scholar 

  18. Navas-Acien A, Tellez-Plaza M, Guallar E, Muntner P, Silbergeld E, Jaar B, Weaver V (2009) Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis. Am J Epidemiol 170(9):1156–1164

    PubMed  PubMed Central  Google Scholar 

  19. Kim Y, Lee BK (2012) Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data. Environ Res 118:124–129

    CAS  PubMed  Google Scholar 

  20. Scinicariello F, Abadin HG, Murray HE (2011) Association of low-level blood lead and blood pressure in NHANES 1999-2006. Environ Res 111(8):1249–1257

    CAS  PubMed  Google Scholar 

  21. Lee BK, Ahn J, Kim NS, Lee CB, Park J, Kim Y (2016) Association of blood pressure with exposure to lead and cadmium: analysis of data from the 2008-2013 Korean National Health and Nutrition Examination Survey. Biol Trace Elem Res 174(1):40–51

    CAS  PubMed  Google Scholar 

  22. Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H (2000) Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study. J Rheumatol 27(7):1708–1712

    CAS  PubMed  Google Scholar 

  23. Krishnan E, Lingala B, Bhalla V (2012) Low-level lead exposure and the prevalence of gout: an observational study. Ann Intern Med 157(4):233–241

    PubMed  Google Scholar 

  24. Dai H, Huang Z, Deng Q, Li Y, Xiao T, Ning X, Lu Y, Yuan H (2015) The effects of Lead exposure on serum uric acid and hyperuricemia in Chinese adults: a cross-sectional study. Int J Environ Res Public Health 12(8):9672–9682

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Jung W, Kim Y, Lihm H, Kang J (2019) Associations between blood lead, cadmium, and mercury levels with hyperuricemia in the Korean general population: a retrospective analysis of population-based nationally representative data. Int J Rheum Dis 22(8):1435–1444

    CAS  PubMed  Google Scholar 

  26. Sun H, Wang N, Chen C, Nie X, Han B, Li Q, Zhu C, Chen Y, Xia F, Chen Y (2017) Cadmium exposure and its association with serum uric acid and hyperuricemia. Sci Rep 7(1):1–8

    Google Scholar 

  27. Jarup L, Persson B, Elinder CG (1995) Decreased glomerular filtration rate in solderers exposed to cadmium. Occup Environ Med 52(12):818–822

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Nordberg GF, Nogawa K, Nordberg M (2014) Cadmium. In: Nordberg GF, Fowler BA, Nordberg M (eds) Handbook on the toxicology of metals. Academic Press, Amsterdam, pp 668–716

    Google Scholar 

  29. Thomas LD, Hodgson S, Nieuwenhuijsen M, Jarup L (2009) Early kidney damage in a population exposed to cadmium and other heavy metals. Environ Health Perspect 117(2):181–184

    CAS  PubMed  Google Scholar 

  30. Ferraro PM, Costanzi S, Naticchia A, Sturniolo A, Gambaro G (2010) Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006. BMC Public Health 10:304

    PubMed  PubMed Central  Google Scholar 

  31. Hwangbo Y, Weaver VM, Tellez-Plaza M, Guallar E, Lee BK, Navas-Acien A (2011) Blood cadmium and estimated glomerular filtration rate in Korean adults. Environ Health Perspect 119(12):1800–1805

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Eum KD, Lee MS, Paek D (2008) Cadmium in blood and hypertension. Sci Total Environ 407(1):147–153

    CAS  PubMed  Google Scholar 

  33. Lee BK, Kim Y (2012) Association of blood cadmium with hypertension in the Korean general population: analysis of the 2008-2010 Korean National Health and Nutrition Examination Survey data. Am J Ind Med 55(11):1060–1067

    CAS  PubMed  Google Scholar 

  34. ATSDR (1999) Toxicological profile for mercury (update). US Agency for Toxic Substances and Disease Registry, Atlanta

  35. Friberg L (1991) Environmental Health Criteria 118; inorganic mercury. WHO, Geneva

  36. Lee H, Kim Y, Sim CS, Ham JO, Kim NS, Lee BK (2014) Associations between blood mercury levels and subclinical changes in liver enzymes among South Korean general adults: analysis of 2008-2012 Korean national health and nutrition examination survey data. Environ Res 130:14–19

    CAS  PubMed  Google Scholar 

  37. Jarup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182

    PubMed  Google Scholar 

  38. Mozaffarian D, Rimm EB (2006) Fish intake, contaminants, and human health evaluating the risks and the benefits. JAMA 296(15):1885–1899

    CAS  PubMed  Google Scholar 

  39. Lee BK, Kim Y (2012) Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: analysis of 2008-2009 Korean National Health and Nutrition Examination Survey data. Environ Res 112:155–163

    CAS  PubMed  Google Scholar 

  40. World Health Organization (2000) The Asia-Pacific perspective: redefining obesity and its treatment. Health Communications Australia, Sydney

  41. World Health Organization (2010) Global recommendations on physical activity for health. World Health Organization, Geneva

    Google Scholar 

  42. Jeong T-D, Lee W, Chun S, Lee SK, Ryu J-S, Min W-K, Park JS (2013) Comparison of the MDRD study and CKD-EPI equations for the estimation of the glomerular filtration rate in the Korean general population: the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010. Kidney Blood Press Res 37(4–5):443–450

    CAS  PubMed  Google Scholar 

  43. National Toxicology Program (2012) NTP Monograph: health effects of low-level lead. Research Triangle Park, National Toxicology Program, NC, USA

  44. American Conference of Governmental Industrial Hygienists (2018) Documentation of the threshold limit values and biological exposure indices, 7th edition - 2017 Supplement. ACGIH, Cincinnati

  45. Centers for Disease Control and Prevention (2009) Fourth national report on human exposure to environmental chemicals updated table [https://www.cdc.gov/exposurereport/index.html]. Accessed 3 Feb 2020

  46. Ahn J, Kim NS, Lee BK, Oh I, Kim Y (2019) Changes of atmospheric and blood concentrations of Lead and cadmium in the general population of South Korea from 2008 to 2017. Int J Environ Res Public Health 16(12):2096

  47. Heitland P, Koster HD (2006) Biomonitoring of 37 trace elements in blood samples from inhabitants of northern Germany by ICP-MS. J Trace Elem Med Biol 20(4):253–262

    CAS  PubMed  Google Scholar 

  48. Becker K, Kaus S, Krause C, Lepom P, Schulz C, Seiwert M, Seifert B (2002) German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. Int J Hyg Environ Health 205(4):297–308

    PubMed  Google Scholar 

  49. Schulz C, Wilhelm M, Heudorf U, Kolossa-Gehring M, Human Biomonitoring Commission of the German Federal Environment A (2011) Update of the reference and HBM values derived by the German Human Biomonitoring Commission. Int J Hyg Environ Health 215(1):26–35

    CAS  PubMed  Google Scholar 

  50. Moon CS, Zhang ZW, Shimbo S, Watanabe T, Moon DH, Lee CU, Lee BK, Ahn KD, Lee SH, Ikeda M (1995) Dietary intake of cadmium and lead among the general population in Korea. Environ Res 71(1):46–54

    CAS  PubMed  Google Scholar 

  51. Ikeda M, Zhang ZW, Shimbo S, Watanabe T, Nakatsuka H, Moon CS, Matsuda-Inoguchi N, Higashikawa K (2000) Urban population exposure to lead and cadmium in east and south-east Asia. Sci Total Environ 249(1–3):373–384

    CAS  PubMed  Google Scholar 

  52. Korean Ministry of Health and Welfare (2014) The sixth Korean National Health and Nutrition Examination Survey. Korean Ministry of Health and Welfare, Seoul

  53. Kim NS, Ahn J, Lee BK, Park J, Kim Y (2017) Environmental exposures to lead, mercury, and cadmium among South Korean teenagers (KNHANES 2010-2013): body burden and risk factors. Environ Res 156:468–476

    CAS  PubMed  Google Scholar 

  54. Lee BK, Kim Y (2016) Association of blood cadmium level with metabolic syndrome after adjustment for confounding by serum ferritin and other factors: 2008-2012 Korean National Health and Nutrition Examination Survey. Biol Trace Elem Res 171(1):6–16

    CAS  PubMed  Google Scholar 

  55. Scott LLF, Nguyen LM (2011) Geographic region of residence and blood lead levels in US children: results of the National Health and Nutrition Examination Survey. Int Arch Occup Environ Health 84(5):513–522

    CAS  PubMed  Google Scholar 

  56. Satarug S, Garrett SH, Sens MA, Sens DA (2010) Cadmium, environmental exposure, and health outcomes. Environ Health Perspect 118(2):182–190

    CAS  PubMed  Google Scholar 

  57. Dai X, Deng Q, Guo D, Ni L, Li J, Chen Z, Zhang L, Xu T, Song W, Luo Y, Hu L, Hu C, Yi G, Pan Z (2019) Association of urinary metal profiles with serum uric acid: a cross-sectional study of traffic policemen in Wuhan, China. BMJ Open 9(5):e022542

    PubMed  PubMed Central  Google Scholar 

  58. Lai L-H, Chou S-Y, Wu F-Y, Chen JJ-H, Kuo H-W (2008) Renal dysfunction and hyperuricemia with low blood lead levels and ethnicity in community-based study. Sci Total Environ 401(1–3):39–43

    CAS  PubMed  Google Scholar 

  59. Choe S-Y, Kim S-J, Kim H-G, Lee JH, Choi Y, Lee H, Kim Y (2003) Evaluation of estrogenicity of major heavy metals. Sci Total Environ 312(1–3):15–21

    CAS  PubMed  Google Scholar 

  60. Nicholls A, Snaith ML, Scott JT (1973) Effect of oestrogen therapy on plasma and urinary levels of uric acid. Br Med J 1(5851):449–451

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Yahyaoui R, Esteva I, Haro-Mora JJ, Almaraz MC, Morcillo S, Rojo-Martinez G, Martinez J, Gomez-Zumaquero JM, Gonzalez I, Hernando V et al (2008) Effect of long-term administration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons. J Clin Endocrinol Metab 93(6):2230–2233

    CAS  PubMed  Google Scholar 

  62. Ali S, Hussain S, Khan R, Mumtaz S, Ashraf N, Andleeb S, Shakir HA, Tahir HM, Khan MKA, Ulhaq M (2019) Renal toxicity of heavy metals (cadmium and mercury) and their amelioration with ascorbic acid in rabbits. Environ Sci Pollut Res Int 26(4):3909–3920

    CAS  PubMed  Google Scholar 

  63. Nan H, Qiao Q, Dong Y, Gao W, Tang B, Qian R, Tuomilehto J (2006) The prevalence of hyperuricemia in a population of the coastal city of Qingdao, China. J Rheumatol 33(7):1346–1350

    PubMed  Google Scholar 

  64. Li Y, Stamler J, Xiao Z, Folsom A, Tao S, Zhang H (1997) Serum uric acid and its correlates in Chinese adult populations, urban and rural, of Beijing. The PRC-USA collaborative study in cardiovascular and cardiopulmonary epidemiology. Int J Epidemiol 26(2):288–296

    CAS  PubMed  Google Scholar 

  65. Vuorinen-Markkola H, Yki-Jarvinen H (1994) Hyperuricemia and insulin resistance. J Clin Endocrinol Metab 78(1):25–29

    CAS  PubMed  Google Scholar 

  66. Ter Maaten JC, Voorburg A, Heine RJ, Ter Wee PM, Donker AJ, Gans RO (1997) Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects. Clin Sci (Lond) 92(1):51–58

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Occupational Health, Catholic University of Daegu, Gyeongsan, South Korea

    Jungsun Park

  2. Department of Occupational and Environmental Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, # 290-3 Cheonha-dong, Dong-gu, Ulsan, 44033, South Korea

    Yangho Kim

Authors
  1. Jungsun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yangho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Design and concept of the study: Jungsun Park, Yangho Kim

The acquisition, analysis of data for the work: Yangho Kim

Drafting the manuscript of the study: Jungsun Park

Revising manuscript critically: Yangho Kim

Final approval of the version to be published: Jungsun Park, Yangho Kim

Accountability for the accuracy and integrity of any part of this paper: Yangho Kim

Corresponding author

Correspondence to Yangho Kim.

Ethics declarations

This survey was approved by the Institutional Review Board of the Korean Centers for Disease Control and Prevention (approval nos. 2013–07CON-03–4C, 2013–12EXP-03–5C).

Conflict of Interest

The authors declare that they have no conflicts of interest.

Institution and Ethics Approval and Informed Consent

All participants provided written informed consent.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, J., Kim, Y. Associations of Blood Heavy Metals with Uric Acid in the Korean General Population: Analysis of Data from the 2016–2017 Korean National Health and Nutrition Examination Survey. Biol Trace Elem Res 199, 102–112 (2021). https://doi.org/10.1007/s12011-020-02152-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02152-5

Keywords

Search

Navigation