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요비중 또는 크레아티닌 보정에 따른 요중 카드뮴과 신장손상지표와의 관련성 비교

Differences in Urine Cadmium Associations with Renal Damage Markers According to the Adjustment with Specific Gravity or Urinary Creatinine

  • 김용대 (충북대학교 예방의학교실) ;
  • 엄상용 (충북대학교 예방의학교실) ;
  • 임동혁 (충북대학교 예방의학교실) ;
  • 권순길 (충북대학교 내과학교실) ;
  • 박충희 (국립환경과학원 환경건강연구부 환경보건연구과) ;
  • 김근배 (국립환경과학원 환경건강연구부 환경보건연구과) ;
  • 유승도 (국립환경과학원 환경건강연구부 환경보건연구과) ;
  • 최병선 (중앙대학교 예방의학교실) ;
  • 박정덕 (중앙대학교 예방의학교실) ;
  • 김헌 (충북대학교 예방의학교실)
  • Kim, Yong-Dae (Department of Preventive Medicine, Chungbuk National University) ;
  • Eom, Sang-Yong (Department of Preventive Medicine, Chungbuk National University) ;
  • Yim, Dong-Hyuk (Department of Preventive Medicine, Chungbuk National University) ;
  • Kwon, Soon Kil (Department of Internal Medicine, College of Medicine, Chungbuk National University) ;
  • Park, Choong-Hee (Environmental Health Research Division, Environmental Health Research Department, National Institute of Environmental Research) ;
  • Kim, Guen-Bae (Environmental Health Research Division, Environmental Health Research Department, National Institute of Environmental Research) ;
  • Yu, Seung-Do (Environmental Health Research Division, Environmental Health Research Department, National Institute of Environmental Research) ;
  • Choi, Byung-Sun (Department of Preventive Medicine, Chung-Ang University) ;
  • Park, Jung-Duck (Department of Preventive Medicine, Chung-Ang University) ;
  • Kim, Heon (Department of Preventive Medicine, Chungbuk National University)
  • 투고 : 2019.01.03
  • 심사 : 2019.02.18
  • 발행 : 2019.02.28

초록

일반적으로 요중 카드뮴 농도는 요비중 또는 요중 크레아티닌 농도로 보정한 값을 사용해왔다. 그러나 어떤 보정방법이 더 타당한지에 대한 논란은 계속되고 있다. 본 연구에서는 비교적 큰 규모의 일반인구집단을 대상으로 요중 카드뮴농도와 각종 신장손상지표들과의 관련성을 평가함에 있어 요비중 보정 방법과 요중 크레아티닌 보정 방법 중 어느 방법이 더 타당한지 비교 평가하였다. 1,086명의 자원자 중 신장질환의 질병력이 있는 사람을 제외한 862명이 최종적으로 연구대상에 포함되었다. 대상자들로부터 측정한 요중 카드뮴 농도 및 malondialdehyde (MDA), N-acetyl-${\beta}$-D-glucosaminidase 농도, 혈중 크레아티닌을 이용하여 산출한 사구체여과율 등의 신장손상지표들간의 관련성을 평가하였다. 연구 결과, 요중 크레아티닌 농도보다는 요비중으로 보정한 카드뮴 농도가 각종 신장손상지표와 높은 상관성이 있음을 보여주었다. 특히, 요비중 보정 카드뮴 농도는 요중 MDA 농도와 양의 상관관계를, 사구체여과율과는 음의 상관관계를 보여주었다. 이러한 결과는 일반인구집단에서 카드뮴 노출이 많아질수록 사구체여과율이 감소함을 의미하며 이러한 기전에서 산화적스트레스가 관여하고 있음을 보여준다. 또한, 사구체여과율이 카드뮴 노출에 의한 유용한 신장손상지표 중 하나로 사용될 수 있음을 의미한다.

In general, specific gravity (SG) and urinary creatinine (CR) have been used to adjust urinary cadmium (Cd) concentrations. However, the validity of correction methods has been controversial. We compared the two adjustments to evaluate associations between urinary Cd and various renal damage markers and to evaluate the relationship between urinary Cd concentration and renal disease markers, such as estimated glomerular filtration rate (eGFR), in a relatively large general population sample. Among the 1,086 volunteers who were enrolled in this study, 862 healthy volunteers who did not have kidney disease were included in the final analysis. Urinary Cd, malondialdehyde (MDA), and N-acetyl-${\beta}$-D-glucosaminidase (NAG) concentrations were measured, the creatinine-based eGFR was calculated, and the relationships between these markers were subsequently analyzed. This study showed the use of urinary Cd concentration adjusted with SG rather than with urinary creatinine may be appropriate in studies evaluating renal function based on Cd exposure. Urinary Cd concentration adjusted with SG had a positive correlation with urinary MDA levels and a negative correlation with eGFR. This relationship was relatively stronger in women than in men. This study showed that urinary Cd level was associated with decreased eGFR in the general population, and oxidative stress was likely to act as an intermediator in this process. These results suggest that eGFR can be a very good indicator of kidney damage caused by Cd exposure in the general population.

키워드

SMGHBM_2019_v29n2_265_f0001.png 이미지

Fig. 1. Association between logarithmic urinary cadmium level and urinary malondialdehyde (MDA), N-acetyl-β-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) according to the gender. A, C, E in men; B, D, F in women

Table 1. Characteristics of subjects and their biological parameters according to the gender and urinary cadmium level

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Table 2. Pearson correlation coefficients between logarithmic urinary cadmium (Cd) level and urinary malondialdehyde (MDA), N-acetyl-β-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR)

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Table 3. General linear model for changes in logarithmic eGFR

SMGHBM_2019_v29n2_265_t0003.png 이미지

참고문헌

  1. Agarwal, R. and Chase, S. D. 2002. Rapid, fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 775, 121-126. https://doi.org/10.1016/S1570-0232(02)00273-8
  2. Bernard, A. 2004. Renal dysfunction induced by cadmium: biomarkers of critical effects. Biometals 17, 519-523. https://doi.org/10.1023/B:BIOM.0000045731.75602.b9
  3. Bernard, A. 2008. Cadmium & its adverse effects on human health. Indian J. Med. Res. 128, 557-564.
  4. Buser, M. C., Ingber, S. Z., Raines, N. and Fowler, D. A., Scinicariello, F. 2016. Urinary and blood cadmium and lead and kidney function: NHANES 2007-2012. Int. J. Hyg. Environ. Health 219, 261-267. https://doi.org/10.1016/j.ijheh.2016.01.005
  5. Chung, S., Chung, J. H., Kim, S. J., Koh, E. S., Yoon, H. E., Park, C. W., Chang, Y. S. and Shin, S. J. 2014. Blood lead and cadmium levels and renal function in Korean adults. J. Clin. Exp. Nephrol. 18, 726-734. https://doi.org/10.1007/s10157-013-0913-6
  6. Eom, S. Y., Seo, M. N., Lee, Y. S., Park, K. S., Hong, Y. S., Sohn, S. J., Kim, Y. D., Choi, B. S., Lim, J. A., Kwon, H. J., Kim, H. and Park, J. D. 2017. Low-level environmental cadmium exposure induces kidney tubule damage in the general population of Korean adults. Arch. Environ. Contam. Toxicol. 73, 401-409. https://doi.org/10.1007/s00244-017-0443-4
  7. Godt, J., Scheidig, F., Grosse-Siestrup, C., Esche, V., Brandenburg, P., Reich, A. and Groneberg, D. A. 2006. The toxicity of cadmium and resulting hazards for human health. J. Occup. Med. Toxicol. 1, 22. https://doi.org/10.1186/1745-6673-1-22
  8. Haddam, N., Samira, S., Dumont, X., Taleb, A., Lison, D., Haufroid, V. and Bernard, A. 2011. Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers. Environ. Health 10, 37. https://doi.org/10.1186/1476-069X-10-37
  9. Ikeda, M., Ezaki, T., Tsukahara, T., Moriguchi, J., Furuki, K., Fukui, Y., Okamoto, S., Ukai, H. and Sakurai, H. 2003. Bias induced by the use of creatinine-corrected values in evaluation of beta2-microgloblin levels. Toxicol. Lett. 145, 197-207. https://doi.org/10.1016/S0378-4274(03)00320-5
  10. Jarup, L. and Akesson, A. 2009. Current status of cadmium as an environmental health problem. Toxicol. Appl. Pharmacol. 238, 201-208. https://doi.org/10.1016/j.taap.2009.04.020
  11. Jarup, L., Berglund, M., Elinder, C. G., Nordberg, G. and 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. https://doi.org/10.5271/sjweh.270
  12. Jatlow, P., McKee, S. and O'Malley, S. S. 2003. Correction of urine cotinine concentrations for creatinine excretion: is it useful? Clin. Chem. 49, 1932-1934. https://doi.org/10.1373/clinchem.2003.023374
  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. 2015. Temporal changes in urinary levels of cadmium, N-acetyl-${\beta}$-d-glucosaminidase and ${\beta}$2-microglobulin in individuals in a cadmium-contaminated area. Environ. Toxicol. Pharmacol. 39, 35-41. https://doi.org/10.1016/j.etap.2014.10.016
  14. Klaassen, C. D., Liu, J. and Diwan, B. A. 2009. Metallothionein protection of cadmium toxicity. Toxicol. Appl. Pharmacol. 238, 215-220. https://doi.org/10.1016/j.taap.2009.03.026
  15. Levey, A. S., Coresh, J., Greene, T., Marsh, J., Stevens, L. A., Kusek, J. W. and Van Lente, F. 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. https://doi.org/10.1373/clinchem.2006.077180
  16. Nordberg, G., Jin, T., Wu, X., Lu, J., Chen, L., Liang, Y., Lei, L., Hong, F., Bergdahl, I. A. and Nordberg, M. 2012. Kidney dysfunction and cadmium exposure--factors influencing dose-response relationships. J. Trace Elem. Med. Biol. 26, 197-200. https://doi.org/10.1016/j.jtemb.2012.03.007
  17. Schisterman, E. F., Cole, S. R. and Platt, R. W. 2009. Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology 20, 488-495. https://doi.org/10.1097/EDE.0b013e3181a819a1
  18. Subramanian, K. S., Meranger, J. C. and MacKeen, J. E. 1983. Graphite furnace atomic absorption spectrometry with matrix modification for determination of cadmium and lead in human urine. Anal. Chem. 55, 1064-1067. https://doi.org/10.1021/ac00258a020
  19. Weaver, V. M., Vargas, G. G., Silbergeld, E. K., Rothenberg, S. J., Fadrowski, J. J., Rubio-Andrade, M., Parsons, P. J., Steuerwald, A. J., Navas-Acien, A. and Guallar, E. 2014. Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents. Environ. Res. 132, 226-232. https://doi.org/10.1016/j.envres.2014.04.013