Cadmium-induced renal dysfunction: New mechanism, treatment and prevention

Abstract

Cadmium-induced renal dysfunction has hitherto been regarded as noncurative, with the renal dysfunction occurring when the cadmium concentration in the renal cortex exceeded a critical concentration for the renal cortex, 200 μg/g wet weight. However, we have identified a mechanism that is quite different from the above working hypothesis: cadmium induces hepatic dysfunction through cadmium-induced free radicals in the liver. Hepatic cadmium-thionein is released into the bloodstream upon hepatic dysfunction and enters the renal tubular lumen by freely passing through the renal glomeruli to result in injury to the brush border membrane of the proximal convoluted tubules. The critical concentration of plasma cadmium, an alternative biomarker for cadmium-thionein in the renal proximal tubules, for inducing renal dysfunction was found to be 100 &mu Cd/L and was quite independent of the cadmium level in the renal cortex. Cadmium-induced renal dysfunction was therefore considered reversible following cessation of cadmium exposure, when the renal dysfunction was not so serious, probably as a result of decreased levels of plasma cadmium-thionein. We also succeeded in improving cadmium-induced renal dysfunction through subcutaneous glycyrrhizin administrations, by lowering the plasma cadmium-thionein due to alleviation of the destruction of hepatic cells. We further succeeded in ameliorating cadmium-induced renal dysfunction through administration of acetazolamide, a carbonic anhydrase blocker, due to the depressed plasma cadmium-thionein associated with improvement of the hepatic dysfunction. J. Trace Elem. Exp. Med. 11:275–288, 1998. © 1998 Wiley-Liss, Inc.