Further accumulation of Cd in renal cellular membranes caused by administration of desferrioxamine to Cd-burdened rats

Background. Desferrioxamine (DFO) a chelating agent, is used to treat metal toxicity caused by iron and aluminum in patients on hemodialysis. We hypothesized that DFO could also be used to treat cadrium-induced nephropathy. Animal experiments were therefore performed to explore whether DFO removed cadmium (Cd) from the kidneys of rats with a Cd burden. Methods. Rats received subcutaneous injections of Cd chloride (3 mg Cd/kg per day, days 0–7) followed by DFO (50 mg/kg per day, days 8–14). Levels of Cd were determined in liver, kidneys, and plasma. Enzymes assays and histopathological examination were performed in kidneys. Results. In liver, Cd injections elevated Cd levels; subsequent injections of DFO lowered the Cd levels compared with levels after injections of Cd alone. In kidneys, Cd injections increased levels of total Cd and Cd bound to cellular membranes (Mem-Cd), and decreased leucine aminopeptidase (LAP) activity (a marker of renal injury); subsequent injections of DFO elevated levels of total Cd and Mem-Cd, and lowered LAP activity compared with fundings after the injection of Cd alone. After the injections of Cd alone and DFO following Cd the renal levels of Cd were below the critical concentration required to cause renal injury, since no histopathological changes were observed in the kidney. Conclusion. DFO administration to Cd-burdened rats removed Cd from the liver, but led to accumulation of Cd in the kidneys, particularly in the cellular membranes. These results suggest that if DFO is given long-term to Cd-burdened patients, the Cd level in kidneys, particularly in renal cellular membranes, could reach concentrations that could cause manifest renal injury. Received: April 13, 1998 / Accepted: August 6, 1998