Chronic trimethyltin chloride exposure and the development of kidney stones in rats

摘要

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague–Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 μg kg⁻¹ day⁻¹. Transient behavioral changes were observed in the high-dose group during the first 2weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H⁺/K⁺-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 μg kg⁻¹ day⁻¹ dose group and 3 out of 9 rats in the 131.3 μg kg⁻¹ day⁻¹ dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.