Renal Tubular Function after Reduction of Environmental Cadmium Exposure: A Ten-year Follow-up

Abstract

A prospective follow-up study was carried out to assess the prognosis of renal tubular function after reduction of environmental cadmium exposure. Time-related changes in urinary beta 2-microglobulin and cadmium excretion were followed from 1979 to 1989 in 102 residents of a cadmium-polluted area in Nagasaki, Japan. The average dietary cadmium intake among the study population was more than 200 micrograms/d in 1969, which decreased to approximately half that amount in 1983 because cadmium-polluted paddy fields were replaced with new soil in 1981. The geometric mean urinary beta 2-microglobulin concentration for 28 subjects aged 40 y or older in 1979 increased from 1,135.8 micrograms/g creatinine in 1979 to 1,999.7 micrograms/g creatinine in 1989. A similar tendency was also observed in 16 subjects with urinary beta 2-microglobulin concentrations greater than 1,000 micrograms/g creatinine in 1979, although the statistical significance of the difference did not reach the 5% level, probably because of the small sample size. In 48 persons examined in 1982, 1986, and 1989, the geometric mean of urinary cadmium concentration decreased from 8.49 micrograms/g creatinine in 1982 to 6.03 micrograms/g creatinine in 1989. The tendency for increasing beta 2-microglobulin excretion observed in the present study could not be explained by aging alone. Thus, it was concluded that renal tubular dysfunction caused by environmental cadmium was irreversible and slowly progressive, even after reduction of exposure. Six of 8 subjects who had severe renal dysfunction and who were included in the study died before 1986 and could not be followed. The implication of loss of subjects because of death is also discussed.

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

“…Results of previous investigations have suggested that proteinuria resulting from high cadmium exposures has been irreversible and progressive (13,37), but reversibility of minor renal changes was found among workers following a reduction in cadmium exposure (38). The clinical significance of the observed relationship between low-level urinary cadmium and urinary NAG and AAP is difficult to discern.…”

The Threshold Cadmium Level That Causes a Substantial Increase in .BETA.2-Microglobulin in Urine of General Populations

“…Kido et al (1988) and Iwata et al (1993) reported that the dysfunction of renal tubules after Cd exposure may become irreversible when β 2 -MG-U cr levels exceed 1,000 μ g / g cr. In a long run, an increase in mortality and reduction in life span was also observed among the residents with 1,000 μ g β 2 -MG / g cr in urine (Iwata et al 1991;Nishijo et al 1994;Arisawa et al 2001).…”

“…The group in Area A in the upper-left corner in the figure included many cases of Itai-itai disease patients and suspects who were all at advanced ages (AM age of cases was in a range of 65 to 82 years with the eldest at 91 years; e.g., Kasuya et al 1992;Aoshima 2004). It is conceivable that while Cd-U cr decreased during hospitalization, tubular dysfunction stayed unimproved or even progressed (Kido et al 1988;Iwata et al 1993), so that Cd-U cr levels were relatively low although β 2 -MG-U cr levels were high. In Area B which is just below Area A, there was no case of the patients or suspects (e.g., Ogata et al 1976;Saito et al 1997).…”

The effect of urinary cadmium on cardiovascular fitness as measured by VO2 max in white, black and Mexican Americans

“…Edling et al (1986), reported subjects exposed to 0.5mg Cd/m 3 had induced renal damage in the form of beta 2-microglobunuria [15]. Iwata et al (1993) and Butchet et al (1990) also obtained similar results, these investigators found associations between levels of cadmium exposure with proteinuria and glomerular filtration rate among workers exposed to cadmium oxide in a nickel-cadmium battery manufacturing factory [16,17].…”