Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. 2002 Feb; 110(2): 151–155.
PMCID: PMC1240729
Research Article

Effects of exposure to low levels of environmental cadmium on renal biomarkers.


We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers.

Full Text

The Full Text of this article is available as a PDF (527K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mueller PW, Price RG, Finn WF. New approaches for detecting thresholds of human nephrotoxicity using cadmium as an example. Environ Health Perspect. 1998 May;106(5):227–230. [PMC free article] [PubMed]
  • Mueller PW, Hall WD, Caudill SP, MacNeil ML, Arepally A. An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension. Am J Hypertens. 1995 Nov;8(11):1072–1082. [PubMed]
  • Lauwerys RR, Bernard AM, Roels HA, Buchet JP. Cadmium: exposure markers as predictors of nephrotoxic effects. Clin Chem. 1994 Jul;40(7 Pt 2):1391–1394. [PubMed]
  • Roels H, Djubgang J, Buchet JP, Bernard A, Lauwerys R. Evolution of cadmium-induced renal dysfunction in workers removed from exposure. Scand J Work Environ Health. 1982 Sep;8(3):191–200. [PubMed]
  • Roels HA, Lauwerys RR, Buchet JP, Bernard AM, Vos A, Oversteyns M. Health significance of cadmium induced renal dysfunction: a five year follow up. Br J Ind Med. 1989 Nov;46(11):755–764. [PMC free article] [PubMed]
  • Mueller PW, Paschal DC, Hammel RR, Klincewicz SL, MacNeil ML, Spierto B, Steinberg KK. Chronic renal effects in three studies of men and women occupationally exposed to cadmium. Arch Environ Contam Toxicol. 1992 Jul;23(1):125–136. [PubMed]
  • Goren MP, Wright RK, Horowitz ME. Cumulative renal tubular damage associated with cisplatin nephrotoxicity. Cancer Chemother Pharmacol. 1986;18(1):69–73. [PubMed]
  • Goren MP, Wright RK, Horowitz ME, Crom WR, Meyer WH. Urinary N-acetyl-beta-D-glucosaminidase and serum creatinine concentrations predict impaired excretion of methotrexate. J Clin Oncol. 1987 May;5(5):804–810. [PubMed]
  • Kawada T, Tohyama C, Suzuki S. Significance of the excretion of urinary indicator proteins for a low level of occupational exposure to cadmium. Int Arch Occup Environ Health. 1990;62(1):95–100. [PubMed]
  • Mueller PW, Smith SJ, Steinberg KK, Thun MJ. Chronic renal tubular effects in relation to urine cadmium levels. Nephron. 1989;52(1):45–54. [PubMed]
  • Chia KS, Ong CN, Ong HY, Endo G. Renal tubular function of workers exposed to low levels of cadmium. Br J Ind Med. 1989 Mar;46(3):165–170. [PMC free article] [PubMed]
  • Piscator M. Long-term observations on tubular and glomerular function in cadmium-exposed persons. Environ Health Perspect. 1984 Mar;54:175–179. [PMC free article] [PubMed]
  • Roels HA, Lauwerys RR, Buchet JP, Bernard A. Environmental exposure to cadmium and renal function of aged women in three areas of Belgium. Environ Res. 1981 Feb;24(1):117–130. [PubMed]
  • Mueller PW. Detecting the renal effects of cadmium toxicity. Clin Chem. 1993 May;39(5):743–745. [PubMed]
  • Roels H, Bernard AM, Cárdenas A, Buchet JP, Lauwerys RR, Hotter G, Ramis I, Mutti A, Franchini I, Bundschuh I, et al. Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium. Br J Ind Med. 1993 Jan;50(1):37–48. [PMC free article] [PubMed]
  • Paschal DC, Burt V, Caudill SP, Gunter EW, Pirkle JL, Sampson EJ, Miller DT, Jackson RJ. Exposure of the U.S. population aged 6 years and older to cadmium: 1988-1994. Arch Environ Contam Toxicol. 2000 Apr;38(3):377–383. [PubMed]
  • Yamanaka O, Kobayashi E, Nogawa K, Suwazono Y, Sakurada I, Kido T. Association between renal effects and cadmium exposure in cadmium-nonpolluted area in Japan. Environ Res. 1998 Apr;77(1):1–8. [PubMed]
  • Bernard A, Thielemans N, Roels H, Lauwerys R. Association between NAG-B and cadmium in urine with no evidence of a threshold. Occup Environ Med. 1995 Mar;52(3):177–180. [PMC free article] [PubMed]
  • Järup L, Carlsson MD, Elinder CG, Hellström L, Persson B, Schütz A. Enzymuria in a population living near a cadmium battery plant. Occup Environ Med. 1995 Nov;52(11):770–772. [PMC free article] [PubMed]
  • Järup L, Hellström L, Alfvén T, Carlsson MD, Grubb A, Persson B, Pettersson C, Spång G, Schütz A, Elinder CG. Low level exposure to cadmium and early kidney damage: the OSCAR study. Occup Environ Med. 2000 Oct;57(10):668–672. [PMC free article] [PubMed]
  • Pruszkowska E, Carnrick GR, Slavin W. Direct determination of cadmium in urine with use of a stabilized temperature platform furnace and Zeeman background correction. Clin Chem. 1983 Mar;29(3):477–480. [PubMed]
  • Jung K, Scholz D. An optimized assay of alanine aminopeptidase activity in urine. Clin Chem. 1980 Aug;26(9):1251–1254. [PubMed]
  • LEABACK DH, WALKER PG. Studies on glucosaminidase. 4. The fluorimetric assay of N-acetyl-beta-glucosaminidase. Biochem J. 1961 Jan;78:151–156. [PMC free article] [PubMed]
  • Mueller PW, MacNeil ML, Steinberg KK. Stabilization of alanine aminopeptidase, gamma glutamyltranspeptidase, and N-acetyl-beta-D-glucosaminidase activity in normal urines. Arch Environ Contam Toxicol. 1986 Jul;15(4):343–347. [PubMed]
  • Kowal NE, Zirkes M. Urinary cadmium and beta 2-microglobulin: normal values and concentration adjustment. J Toxicol Environ Health. 1983 Apr-Jun;11(4-6):607–624. [PubMed]
  • Mueller PW, Caudill SP. Urinary albumin excretion in children: factors related to elevated excretion in the United States population. Ren Fail. 1999 May-Jul;21(3-4):293–302. [PubMed]
  • Bernard A, Stolte H, De Broe ME, Mueller PW, Mason H, Lash LH, Fowler BA. Urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins. IV. Current information on interpreting the health implications of tests. Ren Fail. 1997 Jul;19(4):553–566. [PubMed]
  • Bernard A, Lauwerys R. Cadmium, NAG activity, and beta 2-microglobulin in the urine of cadmium pigment workers. Br J Ind Med. 1989 Sep;46(9):679–680. [PMC free article] [PubMed]
  • Fels LM, Bundschuh I, Gwinner W, Jung K, Pergande M, Graubaum HJ, Price RG, Taylor SA, De Broe ME, Nuyts GD, et al. Early urinary markers of target nephron segments as studied in cadmium toxicity. Kidney Int Suppl. 1994 Nov;47:S81–S88. [PubMed]
  • Jin T, Nordberg G, Wu X, Ye T, Kong Q, Wang Z, Zhuang F, Cai S. Urinary N-acetyl-beta-D-glucosaminidase isoenzymes as biomarker of renal dysfunction caused by cadmium in a general population. Environ Res. 1999 Aug;81(2):167–173. [PubMed]
  • Lybarger JA, Lichtveld MY, Amler RW. Biomedical testing of the kidney for persons exposed to hazardous substances in the environment. Ren Fail. 1999 May-Jul;21(3-4):263–274. [PubMed]
  • Jensen GE, Christensen JM, Poulsen OM. Occupational and environmental exposure to arsenic--increased urinary arsenic level in children. Sci Total Environ. 1991 Sep;107:169–177. [PubMed]
  • Iwata K, Saito H, Moriyama M, Nakano A. Renal tubular function after reduction of environmental cadmium exposure: a ten-year follow-up. Arch Environ Health. 1993 May-Jun;48(3):157–163. [PubMed]
  • Roels HA, Van Assche FJ, Oversteyns M, De Groof M, Lauwerys RR, Lison D. Reversibility of microproteinuria in cadmium workers with incipient tubular dysfunction after reduction of exposure. Am J Ind Med. 1997 May;31(5):645–652. [PubMed]
  • Hotz P, Buchet JP, Bernard A, Lison D, Lauwerys R. Renal effects of low-level environmental cadmium exposure: 5-year follow-up of a subcohort from the Cadmibel study. Lancet. 1999 Oct 30;354(9189):1508–1513. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...