Analysis for threshold levels of cadmium in urine that induce tubular dysfunction among women in non-polluted areas in Japan

Int Arch Occup Environ Health. 2003 Apr;76(3):197-204. doi: 10.1007/s00420-002-0390-9. Epub 2002 Dec 19.

Abstract

Objective: To examine if there is a threshold in urinary cadmium concentration that induces elevation in urinary microglobulins.

Methods: The database developed in a previous field survey (Ezaki et al. 2002) was employed. In the survey conducted in 2000 and 2001, more than 10,000 middle-aged women (with no occupational exposure to Cd) in ten prefectures all over Japan gave morning spot urine samples, which were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U), and creatinine (cr). The urinary analyte concentrations were corrected for cr concentration (to be expressed as, e.g., Cd-Ucr), and the data thus obtained were subjected to statistical evaluation. The largest geometric mean (GM) for Cd-Ucr among the ten prefecture was 3.2 microg Cd/g cr, and the maximum Cd-Ucr observed among the women studied was 20.9 microg Cd/g cr.

Results: Both alpha(1)-MG-Ucr and beta(2)-MG-Ucr increased as a function of the increase in Cd-Ucr among all the women and also in sub-populations of narrow age ranges (i.e., 41-50 and 51-60 years), with no apparent threshold Cd-Ucr. Comparison of the cases exceeding cut-off alpha(1)-MG-Ucr and beta(2)-MG-Ucr levels also indicated a Cd dose-dependent increase in the prevalence, similarly without a threshold Cd-Ucr. In addition, such findings were essentially reproducible when elevation in alpha(1)-MG-Ucr and beta(2)-MG-Ucr levels was examined with the three essential elements, especially with Ca-Ucr and Mg-Ucr, although less clearly with Zn-Ucr. The observations as a whole suggest a possibility that the dose-dependent increases in alpha(1)-MG-Ucr and beta(2)-MG-Ucr with no apparent threshold for element concentration is not specific to Cd-Ucr but common to other elements.

Conclusions: No threshold Cd-Ucr was detected in relation to the increases in alpha(1)-MG-Ucr and beta(2)-MG-Ucr. The element dose-dependent increases in the two MGs with no threshold in the element concentration might be not limited to Cd, but common to other elements. Further studies are apparently necessary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cadmium / pharmacology
  • Cadmium / urine*
  • Cadmium Poisoning / urine*
  • Calcium / urine
  • Dose-Response Relationship, Drug
  • Environmental Exposure*
  • Environmental Monitoring
  • Female
  • Humans
  • Japan
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / urine*
  • Kidney Tubules / drug effects
  • Magnesium / urine
  • Middle Aged
  • Zinc / urine

Substances

  • Cadmium
  • Magnesium
  • Zinc
  • Calcium