Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Associations of Low Environmental Exposure to Multiple Metals with Renal Tubular Impairment in Korean Adults

  • Lim, Hyungryul (Department of Preventive Medicine, Dankook University College of Medicine) ;
  • Lim, Ji-ae (Department of Preventive Medicine, Dankook University College of Medicine) ;
  • Choi, Jong Hyuk (Department of Preventive Medicine, Dankook University College of Medicine) ;
  • Kwon, Ho-jang (Department of Preventive Medicine, Dankook University College of Medicine) ;
  • Ha, Mina (Department of Preventive Medicine, Dankook University College of Medicine) ;
  • Kim, Heon (Department of Preventive Medicine, Chungbuk National University College of Medicine) ;
  • Park, Jung-duck (Department of Preventive Medicine, Chung-ang University College of Medicine)
  • Received : 2015.12.01
  • Accepted : 2016.01.03
  • Published : 2016.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

Recently several studies reported that the renal toxicity of lead (Pb) and cadmium (Cd) may exist in even a low level exposure. In terms of the deterioration of tubular function, it affects the loss of divalent metals and leads to other complications, so renal tubular effect of heavy metals should be well managed. Considering the exposure to heavy metals in reality, it is hard to find the case that human is exposed to only one heavy metal. We designed a cross-sectional study using Korean Research Project on the Integrated Exposure Assessment (KRIEFS) data to investigate the renal effects of multiple metal exposure in general population. We used blood Pb and urinary Cd as exposure measures, and urinary N-acetyl-${\beta}$-D-glucosaminidase (NAG) and ${\beta}_2$-microglobulin (${\beta}_2$-MG) as renal tubular impairment outcome. We conducted linear regression to identify the association between each heavy metal and urinary NAG and ${\beta}_2$-MG. And then, we conducted linear regression including the interaction term. Of 1953 adults in KRIEFS (2010~2011), the geometric mean of blood Pb and urinary Cd concentration was $2.21{\mu}g/dL$ (geometric $SD=1.49{\mu}g/dL$) and $1.08{\mu}g/g\;cr$ (geometric $SD=1.98{\mu}g/g\;cr$), respectively. In urinary Cd, the strength of the association was also high after adjusting (urinary NAG: ${\beta}=0.44$, p < 0.001; urinary ${\beta}_2$-MG: ${\beta}=0.13$, p = 0.002). Finally, we identified the positive interactions for the two renal biomarkers. The interaction effect of the two heavy metals of ${\beta}_2$-MG was greater than that of NAG. It is very important in public health perspective if the low level exposure to multiple heavy metals has an interaction effect on kidney. More epidemiological studies for the interaction and toxicological studies on the mechanism are needed.

Keywords

References

  1. Burns, M.S. and Gerstenberger, S.L. (2014) Implications of the new Centers for Disease Control and Prevention blood lead reference value. Am. J. Public Health, 104, e27-33.
  2. Joint FAO/WHO Expert Committee on Food Additives (JECFA). (2010) Evaluation of certain food additives and contaminants (Seventy-first report). WHO Tech. Rep. Ser., 960.
  3. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). (2009) Cadmium in food - Scientific opinion of the Panel on Contaminants in the Food Chain. EFSA J., 980, 1-139.
  4. Son, J.Y., Lee, J., Paek, D. and Lee, J.T. (2009) Blood levels of lead, cadmium, and mercury in the Korean population: results from the Second Korean National Human Exposure and Bio-monitoring Examination. Environ. Res., 109, 738-744. https://doi.org/10.1016/j.envres.2009.03.012
  5. Korean Centers for Disease Control and Prevention. (2011) 2010 National Health Statistics, Korean National Health and Nutrition Examination Survey (KNHANES). First year.
  6. U.S. Centers for Disease Control and Prevention. (2015) Fourth national report on human exposure to environmental chemicals.
  7. Becker, K., Kaus, S., Krause, C., Lepom, P., Schulz, C., Seiwert, M. and Seifert, B. (2002) German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. Int. J. Hyg. Environ. Health, 205, 297-308. https://doi.org/10.1078/1438-4639-00155
  8. Skalova, S. (2005) The diagnostic role of urinary N-acetylbeta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment. Acta Med. (Hradec Kralove), 48, 75-80.
  9. Zeng, X., Hossain, D., Bostwick, D.G., Herrera, G.A. and Zhang, P.L. (2014) Urinary beta2-Microglobulin Is a Good Indicator of Proximal Tubule Injury. J. Biomarkers, 2014, 492838.
  10. Klaassen, C. (2013) Casarett & Doull's Toxicology: The Basic Science of Poisons (Eighth edition). McGraw-Hill Education, pp. 990-995.
  11. Huang, M., Choi, S.J., Kim, D.W., Kim, N.Y., Bae, H.S., Yu, S.D., Kim, D.S., Kim, H., Choi, B.S., Yu, I.J. and Park, J.D. (2013) Evaluation of factors associated with cadmium exposure and kidney function in the general population. Environ. Toxicol., 28, 563-570. https://doi.org/10.1002/tox.20750
  12. Suwazono, Y., Nogawa, K., Uetani, M., Miura, K., Sakata, K., Okayama, A., Ueshima, H., Stamler, J. and Nakagawa, H. (2011) Application of hybrid approach for estimating the benchmark dose of urinary cadmium for adverse renal effects in the general population of Japan. J. Appl. Toxicol., 31, 89-93. https://doi.org/10.1002/jat.1582
  13. Kim, Y.D., Yim, D.H., Eom, S.Y., Moon, S.I., Park, C.H., Kim, G.B., Yu, S.D., Choi, B.S., Park, J.D. and Kim, H. (2014) Differences in the susceptibility to cadmium-induced renal tubular damage and osteoporosis according to sex. Environ. Toxicol. Pharmacol., 38, 272-278. https://doi.org/10.1016/j.etap.2014.06.002
  14. Kim, Y.D., Yim, D.H., Eom, S.Y., Moon, S.I., Park, C.H., Kim, G.B., Yu, S.D., Choi, B.S., Park, J.D. and Kim, H. (2015) Temporal changes in urinary levels of cadmium, Nacetyl-beta-d-glucosaminidase and beta2-microglobulin in individuals in a cadmium-contaminated area. Environ. Toxicol. Pharmacol., 39, 35-41. https://doi.org/10.1016/j.etap.2014.10.016
  15. Nishijo, M., Suwazono, Y., Ruangyuttikarn, W., Nambunmee, K., Swaddiwudhipong, W., Nogawa, K. and Nakagawa, H. (2014) Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand. BMC Public Health, 14, 702. https://doi.org/10.1186/1471-2458-14-702
  16. Wang, G. and Fowler, B.A. (2008) Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic. Toxicol. Appl. Pharmacol., 233, 92-99. https://doi.org/10.1016/j.taap.2008.01.017
  17. Navas-Acien, A., Tellez-Plaza, M., Guallar, E., Muntner, P., Silbergeld, E., Jaar, B. and Weaver, V. (2009) Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis. Am. J. Epidemiol., 170, 1156-1164. https://doi.org/10.1093/aje/kwp248
  18. Trzeciakowski, J.P., Gardiner, L. and Parrish, A.R. (2014) Effects of environmental levels of cadmium, lead and mercury on human renal function evaluated by structural equation modeling. Toxicol. Lett., 228, 34-41. https://doi.org/10.1016/j.toxlet.2014.04.006
  19. Hambach, R., Lison, D., D'Haese, P.C., Weyler, J., De Graef, E., De Schryver, A., Lamberts, L.V. and van Sprundel, M. (2013) Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers. Toxicol. Lett., 222, 233-238. https://doi.org/10.1016/j.toxlet.2013.06.218
  20. Lim, J.A., Kwon, H.J., Ha, M., Kim, H., Oh, S.Y., Kim, J.S., Lee, S.A., Park, J.D., Hong, Y.S., Sohn, S.J., Pyo, H., Park, K.S., Lee, K.G., Kim, Y.D., Jun, S. and Hwang, H.S. (2015) Korean research project on the integrated exposure assessment of hazardous substances for food safety. Environ. Health Toxicol., 30, e2015004. https://doi.org/10.5620/eht.e2015004
  21. Barbier, O., Jacquillet, G., Tauc, M., Cougnon, M. and Poujeol, P. (2005) Effect of Heavy Metals on, and Handling by, the Kidney. Nephron Physiol., 99, 105-110. https://doi.org/10.1159/000083981
  22. Garcon, G., Leleu, B., Marez, T., Zerimech, F., Haguenoer, J.M., Furon, D. and Shirali, P. (2007) Biomonitoring of the adverse effects induced by the chronic exposure to lead and cadmium on kidney function: usefulness of alpha-glutathione S-transferase. Sci. Total Environ., 377, 165-172. https://doi.org/10.1016/j.scitotenv.2007.02.002
  23. Shelley, R., Kim, N.S., Parsons, P., Lee, B.K., Jaar, B., Fadrowski, J., Agnew, J., Matanoski, G.M., Schwartz, B.S., Steuerwald, A., Todd, A., Simon, D. and Weaver, V.M. (2012) Associations of multiple metals with kidney outcomes in lead workers. Occup. Environ. Med., 69, 727-735. https://doi.org/10.1136/oemed-2012-100765
  24. Korean Ministry of Food and Drug Safety. (2012) A study on the integrated exposure to hazardous materials for safety control.

Cited by

  1. Shedding New Lights with the Breakthrough Ideas to Understand Current Trends in Modern Toxicology vol.32, pp.1, 2016, https://doi.org/10.5487/TR.2016.32.1.001
  2. Non-cancer, cancer, and dermal sensitization risk assessment of heavy metals in cosmetics vol.81, pp.11, 2018, https://doi.org/10.1080/15287394.2018.1451191