Skip to main content
Log in

Low-Level Environmental Cadmium Exposure Induces Kidney Tubule Damage in the General Population of Korean Adults

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Cadmium (Cd) is the most potent nephrotoxic heavy metal and may affect bone; it also has a long biological half-life in the human body. This study was designed to assess the effect of environmental low-level Cd exposure on kidney function and bone in the general population. The subjects of this cross-sectional study were 1907 healthy Korean adults who had not been exposed to Cd occupationally. We analyzed the concentrations of Cd in the urine, markers of renal tubule damage, such as β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) activity in the urine, calculated the estimated glomerular filtration rate (eGFR) using serum creatinine, and measured bone mineral density (BMD). Also, we analyzed malondialdehyde (MDA) levels in the urine. The geometric mean concentration of Cd in urine was higher in women (1.36 μg/g creatinine) than in men (0.82 μg/g creatinine). Urinary Cd was significantly positively correlated with urinary β2-MG and NAG activity, whereas it was negatively correlated with eGFR and BMD. The risk of renal tubule damage was significantly associated with urine Cd level, and the association remained significant after controlling for various confounding variables. However, no association was observed between urinary Cd level and glomerular dysfunction or bone damage. The concentration of MDA was increased with urinary Cd level in a dose-dependent manner. These findings suggest that low-level environmental Cd exposure may cause microscopic damage to renal tubules through oxidative stress but might not impair kidney glomeruli or bones.

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

  • Agarwal R, Chase SD (2002) Rapid, fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples. J Chromatogr B Analyt Technol Biomed Life Sci 775:121–126

    Article  CAS  Google Scholar 

  • Akerstrom M, Sallsten G, Lundh T, Barregard L (2013) Associations between urinary excretion of cadmium and proteins in a nonsmoking population: renal toxicity or normal physiology? Environ Health Perspect 121:187–191

    Google Scholar 

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

    Article  Google Scholar 

  • Akesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skerfving S, Vahter M (2006) Cadmium-induced effects on bone in a population-based study of women. Environ Health Perspect 114:830–834

    Article  Google Scholar 

  • Alfvén T, Elinder CG, Carlsson MD, Grubb A, Hellström L, Persson B, Pettersson C, Spång G, Schütz A, Järup L (2000) Low-level cadmium exposure and osteoporosis. J Bone Miner Res 15:1579–1586

    Article  Google Scholar 

  • ATSDR (2012) Toxicological profile for cadmium. Division of Toxicology, Agency for Toxic Substances and Disease Registry, Atlanta

    Google Scholar 

  • Becker K, Schulz C, Kaus S, Seiwert M, Seifert B (2003) German Environmental Survey 1998 (GerES III): environmental pollutants in the urine of the German population. Int J Hyg Environ Health 206:15–24

    Article  CAS  Google Scholar 

  • Bernard A (2004) Renal dysfunction induced by cadmium: biomarkers of critical effects. Biometals 17:519–523

    Article  CAS  Google Scholar 

  • Bernard A (2008) Cadmium & its adverse effects on human health. Indian J Med Res 128:557–564

    CAS  Google Scholar 

  • Borné Y, Söderholm M, Barregard L, Fagerberg B, Persson M, Melander O, Thévenod F, Hedblad B, Engström G (2016) Genome wide association study identifies two loci associated with cadmium in erythrocytes among never-smokers. Hum Mol Genet 25:2342–2348

    Article  Google Scholar 

  • Brzóska MM, Moniuszko-Jakoniuk J (2005) Bone metabolism of male rats chronically exposed to cadmium. Toxicol Appl Pharmacol 207:195–211

    Article  Google Scholar 

  • Buser MC, Ingber SZ, Raines N, Fowler DA, Scinicariello F (2016) Urinary and blood cadmium and lead and kidney function: NHANES 2007–2012. Int J Hyg Environ Health 219:261–267

    Article  CAS  Google Scholar 

  • Byber K, Lison D, Verougstraete V, Dressel H, Hotz P (2016) Cadmium or cadmium compounds and chronic kidney disease in workers and the general population: a systematic review. Cri Rev Toxicol 46:191–240

    Article  CAS  Google Scholar 

  • Campbell JR, Auinger P (2007) The association between blood lead levels and osteoporosis among adults—results from the third national health and nutrition examination survey (NHANES III). Environ Health Perspect 115:1018–1022

    Article  CAS  Google Scholar 

  • Chaumont A, Nickmilder M, Dumont X, Lundh T, Skerfving S, Bernard A (2012) Associations between proteins and heavy metals in urine at low environmental exposures: evidence of reverse causality. Toxicol Lett 210:345–352

    Article  CAS  Google Scholar 

  • EFSA (2009) Cadmium in food. Scientific opinion of the panel on contaminants in the food chain. EFSA J 980:1–139

    Google Scholar 

  • Eom SY, Choi SH, Ahn SJ, Kim DK, Kim DW, Lim JA, Choi BS, Shin HJ, Yun SW, Yoon HJ, Kim YM, Hong YS, Yun YW, Sohn SJ, Kim H, Park KS, Pyo HS, Kim H, Oh SY, Kim J, Lee SA, Ha M, Kwon HJ, Park JD (2014) Reference levels of blood mercury and association with metabolic syndrome in Korean adults. Int Arch Occup Environ Health 87:501–513

    Article  CAS  Google Scholar 

  • Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y, Ukai H, Okamoto S, Sakurai H, Honda S, Ikeda M (2003) No clear-cut evidence for cadmium-induced renal tubular dysfunction among over 10,000 women in the Japanese general population: a nationwide large-scale survey. Int Arch Occup Environ Health 76:186–196

    CAS  Google Scholar 

  • Godt J, Scheidig F, Grosse-Siestrup C, Esche V, Brandenburg P, Reich A, Groneberg DA (2006) The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol 1:22

    Article  Google Scholar 

  • Horiguchi H, Oguma E, Sasaki S, Miyamoto K, Ikeda Y, Machida M, Kayama F (2005) Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers. Environ Res 97:83–92

    Article  CAS  Google Scholar 

  • Hornung RW, Reed LD (1990) Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg 5:46–51

    Article  CAS  Google Scholar 

  • Huang M, Choi SJ, Kim DW, Kim NY, Bae HS, Yu SD, Kim DS, Kim H, Choi BS, Yu IJ, Park JD (2013) Evaluation of factors associated with cadmium exposure and kidney function in the general population. Environ Toxicol 28:563–570

    Article  CAS  Google Scholar 

  • 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 119:1800–1805

    Article  CAS  Google Scholar 

  • Ikeda M, Moriguchi J, Sakuragi S, Ohashi F (2013) Association of past diseases with levels of cadmium and tubular dysfunction markers in urine of adult women in non-polluted areas in Japan. Int Arch Occup Environ Health 86:343–355

    Article  CAS  Google Scholar 

  • Järup L, Akesson A (2009) Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol 238:201–208

    Article  Google Scholar 

  • Järup L, Berglund M, Elinder CG, Nordberg G, Vahter M (1998) Health effects of cadmium exposure—a review of the literature and a risk estimate. Scand J Work Environ Health 24:1–51

    Article  Google Scholar 

  • Jin T, Nordberg G, Ye T, Bo M, Wang H, Zhu G, Kong Q, Bernard A (2004) Osteoporosis and renal dysfunction in a general population exposed to cadmium in China. Environ Res 96:353–359

    Article  CAS  Google Scholar 

  • Kazantzis G (2004) Cadmium, osteoporosis and calcium metabolism. Biometals 17:493–498

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kjellstrom T (1992) Mechanism and epidemiology of bone effects of cadmium. IARC Sci Publ 118:301–310

    Google Scholar 

  • Klaassen CD, Liu J, Diwan BA (2009) Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 238:215–220

    Article  CAS  Google Scholar 

  • Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F, Collaboration Chronic Kidney Disease Epidemiology (2007) Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53:766–772

    Article  CAS  Google Scholar 

  • Lim JA, Kwon HJ, Ha M, Kim H, Oh SY, Kim JS, Lee SA, Park JD, Hong YS, Sohn SJ, Pyo H, Park KS, Lee KG, Kim YD, Jun S, Hwang MS (2015) Korean research project on the integrated exposure assessment of hazardous substances for food safety. Environ Health Toxicol 30:e2015004

    Article  Google Scholar 

  • Moon C-S, Lee CK, Lee JT, Kim JM, Paik J-M, Ikeda M (2012) Time trends in dietary cadmium intake of Korean women. Toxicol Res 1:145–150

    Article  CAS  Google Scholar 

  • Moulis JM, Thévenod F (2010) New perspectives in cadmium toxicity: an introduction. Biometals 23:763–768

    Article  CAS  Google Scholar 

  • Myong JP, Kim HR, Baker D, Choi B (2012) Blood cadmium and moderate-to-severe glomerular dysfunction in Korean adults: analysis of KNHANES 2005–2008 data. Int Arch Occup Environ Health 85:885–893

    Article  CAS  Google Scholar 

  • NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Article  Google Scholar 

  • Nordberg GF (2009) Historical perspectives on cadmium toxicology. Toxicol Appl Pharmacol 238:192–200

    Article  CAS  Google Scholar 

  • Prozialeck WC, Edwards JR (2010) Early biomarkers of cadmium exposure and nephrotoxicity. Biometals 23:793–809

    Article  CAS  Google Scholar 

  • Ryu DY, Lee SJ, Park DW, Choi BS, Klaassen CD, Park JD (2004) Dietary iron regulates intestinal cadmium absorption through iron transporters in rats. Toxicol Lett 152:19–25

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Shaikh ZA, Vu TT, Zaman K (1999) Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants. Toxicol Appl Pharmacol 154:256–263

    Article  CAS  Google Scholar 

  • Thévenod F, Friedmann JM (1999) Cadmium-mediated oxidative stress in kidney proximal tubule cells induces degradation of Na+/K(+)-ATPase through proteasomal and endo-/lysosomal proteolytic pathways. FASEB J 13:1751–1761

    Google Scholar 

  • Thijssen S, Cuypers A, Maringwa J, Smeets K, Horemans N, Lambrichts I, Van Kerkhove E (2007) Low cadmium exposure triggers a biphasic oxidative stress response in mice kidneys. Toxicology 236:29–41

    Article  CAS  Google Scholar 

  • Trzcinka-Ochocka M, Jakubowski M, Szymczak W, Janasik B, Brodzka R (2010) The effects of low environmental cadmium exposure on bone density. Environ Res 110:286–293

    Article  CAS  Google Scholar 

  • Tsuchiya K (1969) Causation of Ouch-Ouch Disease (Itai-Itai Byõ): an introductory review. II. Epidemiology and evaluation. Keio J Med 18:195–211

    Article  CAS  Google Scholar 

  • Wallin M, Barregard L, Sallsten G, Lundh T, Karlsson MK, Lorentzon M, Ohlsson C, Mellström D (2016) Low-level cadmium exposure is associated with decreased bone mineral density and increased risk of incident fractures in elderly men: the MrOS Sweden study. J Bone Miner Res 31:732–741

    Article  CAS  Google Scholar 

  • Wang D, Sun H, Wu Y, Zhou Z, Ding Z, Chen X, Xu Y (2016) Tubular and glomerular kidney effects in the Chinese general population with low environmental cadmium exposure. Chemosphere 147:3–8

    Article  CAS  Google Scholar 

  • Weaver VM, Kotchmar DJ, Fadrowski JJ, Silbergeld EK (2016) Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment? J Expo Sci Environ Epidemiol 26:1–8

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by a Grant (14162MFDS655) from the Ministry of Food and Drug Safety in 2015.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jung-Duck Park.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eom, SY., Seo, MN., Lee, YS. et al. Low-Level Environmental Cadmium Exposure Induces Kidney Tubule Damage in the General Population of Korean Adults. Arch Environ Contam Toxicol 73, 401–409 (2017). https://doi.org/10.1007/s00244-017-0443-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-017-0443-4

Navigation