Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure

Abstract

Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women's health survey in southern Sweden (Women's Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53-64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 microg/L) and urine (0.52 microg/L; density adjusted = 0.67 microg/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-beta-D-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 microg/L (0.8 microg/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.

Figure 1

Associations (crude) between urinary NAG (A), creatinine clearance (B), and GFR (C) and urinary cadmium (categorized) in a population-based study from 1999 through early 2000 on 816 women in southern Sweden. Boxes indicate 25th, 50th (solid line), and 75th percentiles, and whiskers indicate minimum and maximum, excluding outliers (circles; a few, not shown in the figure but included in all the calculations). Numbers inside boxes indicate the number of samples. The dashed line indicates the median in the lowest urinary cadmium exposure category. p-Values for differences between the lowest exposure group and the following groups are indicated (Dunnett’s test including the significant confounders and covariates according to Table 3).