Relationships of environmental cadmium exposure with changes of renal function and urinary transforming growth factor-β1

Background The chronic toxicity of cadmium far exceeds that of other heavy metals. Cadmium mainly accumulates in the kidney, and its toxic effects on renal function and related doseresponse relationship need to be further studied.

Objective This experiment evaluates the relationships of environmental cadmium exposure with the changes of renal function and urinary transforming growth factor (TGF)-β1 levels.

Methods A cross-sectional study was used to recruit 229 residents of a cadmium-polluted irrigation area (a low-level environmental cadmium exposure area where soil cadmium level was 0.238 mg·kg^-1, slightly lower than the national environmental quality standard limit for soil cadmium of 0.3 mg·kg^-1) and 212 residents of a non-cadmium-polluted area (where soil cadmium level was 0.077 mg·kg^-1) in North China. The participants had lived there for more than 10 years. Their peripheral blood and urine samples were collected, the urinary cadmium (UCd), urinary transforming growth factor-β1 (UTGF-β1), urinary micro-albumin (UALB), urinary N-acetyl-β-D-glucosaminidase (UNAG), and serum and urinary creatinine levels were measured, and estimated glomerular filtration rate (eGFR) was calculated. The indicators were expressed as median (M) and the 25th and 75th percentages (P₂₅, P₇₅). Kruskal-Wallis test was used to compare the renal function indexes and urinary TGF-β1 levels at different UCd levels. Spearman rank correlation analysis was adopted to assess the correlations of UCd with renal function indexes and urinary TGF-β1. The relationships of UCd with urinary TGF-β1, UALB, UNAG, and eGFR were analyzed by restricted cubic spline after adjusting for gender and age.

Results The UCd level of residents in the cadmium-polluted area was 1.07 (0.57, 2.61) μg·g^-1 (adjusted for UCr, thereafter), which was higher than that in the non-cadmium-polluted area0.75 (0.43, 1.21) μg·g^-1, P < 0.001. The levels of UNAG and UALB of residents in the cadmiumpolluted area were 17.26 (12.29, 26.11) U·g^-1 and 12.97 (8.59, 20.88) mg·g^-1, which were higher than those in the non-cadmium-polluted area; the eGFR and urinary TGF-β1 levels were 56.38 (48.63, 63.90) mL·min^-1 and 21.22 (12.01, 36.26) ng·L^-1, lower than those in the noncadmium-polluted area (all P < 0.05). There were significant differences in renal function indexes among the residents grouped by quartiles of UCd levels; specifically, with the increase of UCd levels, UNAG, UALB, and urinary TGF-β1 increased, while eGFR decreased. The results of restricted cubic spline analysis revealed that the correlations of UCd with UNAG and urinary TGF-β1 (χ²=8.24, P=0.0162; χ²=17.90, P < 0.001) were significant and non-linear (χ²_non-linear=3.93, P_non-linear=0.047 6; χ²_non-linear=8.60, P_non-linear=0.003 4). When UCd was higher than 0.750 μg·g^-1, UNAG and TGF-β1 showed an increasing trend.

Conclusion Long-term low-dose cadmium exposure may cause adverse effects on renal function and urinary TGF-β1 levels.