The cellular pathology of the kidney is studied in rats following exposure to toxic metals. A series of experiments is being conducted to determine the influence of essential trace metal metabolism on metal nephrotoxicity. Metabolic parameters and indicators of toxicity measured include cell ultrastructure, toxic and trace metal burden and excretion, changes in metal-binding protein, e.g., metallothionein. Results to date indicate that: o Lead exposure increases urinary zinc in a dose and exposure length-dependent manner; urinary calcium is increased at the highest lead dose only. o Calcium content of kidney is normally low, but there is a discontinuous increase in calcium concentration, indicative of renal cell injury, if blood lead concentration exceeds 45 Mug/dl. o Increased blood pressure occurs in rats after moderate exposure to lead for 12 months (mean blood lead, 45 Mug/dl). o Animals injected with cadmium have increased metallothionein content of liver and kidney with liver metallothionein concentration two-fold greater then kidney. Zinc deficiency results in less increase in kidney metallothionein with cadmium exposure, greater increase in non-metallothionein bound cadmium, and increased susceptibility to cadmium nephrotoxicity. The purpose of these studies is twofold: one is to determine biologic indicators of renal toxicity in response to toxic metal exposure. The second is to determine the role of metal binding proteins and essential metals on toxicity. From these studies the influence of various factors on risk to exposure to toxic metals may be estimated. The identification of indicators of exposure and biologic effect may have application in prevention of toxicity.
