CADMIUM-INDUCED RENAL DYSFUNCTION - NEW MECHANISM, TREATMENT AND PREVENTION

Cadmium-induced renal dysfunction has hitherto been regarded as noncur ative, with the renal dysfunction occurring when the cadmium concentra tion in the renal cortex exceeded a critical concentration for the ren al cortex, 200 mu g/g wet weight. However, we have identified a mechan ism 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 u pon hepatic dysfunction and enters the renal tubular lumen by freely p assing through the renal glomeruli to result in injury to the brush bo rder membrane of the proximal convoluted tubules. The critical concent ration of plasma cadmium, an alternative biomarker for cadmium-thionei n in the renal proximal tubules, for inducing renal dysfunction was fo und to be 100 mu g 8 Cd/L and was quite independent of the cadmium lev el in the renal cortex. Cadmium-induced renal dysfunction was therefor e considered reversible following cessation of cadmium exposure, when the renal dysfunction was not so serious, probably as a result of decr eased levels of plasma cadmium-thionein. We also succeeded in improvin g cadmium-induced renal dysfunction through subcutaneous glycyrrhizin administrations, by lowering the plasma cadmium-thionein due to allevi ation of the destruction of hepatic cells. We further succeeded in ame liorating cadmium-induced renal dysfunction through administration of acetazolamide, a carbonic anhydrase blocker, due to the depressed plas ma cadmium-thionein associated with improvement of the hepatic dysfunc tion. J. Trace Elem. Exp. Med. 11:275-288, 1998. (C) 1998 Wiley-Liss, Inc.