Prolonged
cadmium exposure has been associated with
proteinuria, calcuria and loss of
calcium from bones in humans. Previous studies have shown that kidney uptake of
cadmium in vivo results from proximal tubule absorption of the circulating
cadmium metallothionein complex (
CdMT), and intracellular release of the Cd2+ ion prior to induction of renal
metallothionein. Parenteral administration of
CdMT has been found to selectively damage the proximal tubule cell lysosome system with development of a tubular
proteinuria pattern similar to that observed under chronic exposure conditions. The present studies also demonstrate a concomitant calcuria but no changes in the excretion of other
electrolytes or
glucose using this model. These marked changes in renal
calcium metabolism occurred in the absence of mitochondrial damage, changes in total, Na/K or Mg-stimulated
ATPase activities, renal
ATP levels, membrane 45Ca2+ transport or overt tubule cell
necrosis during an 8 hour period following
CdMT injection.
Proteinuria and calcuria were prevented by prior
zinc induction of the renal MT pool. Data from these studies indicate that renal proximal tubule cell uptake and degradation of the circulating
CdMT complex produces both a marked
proteinuria and calcuria. The calcuria does not appear to stem from changes in renal energy metabolism or membrane transport of this
element but is probably a secondary result of
calcium binding to excreted
proteins which are increased in urine to a similar extent. The studies also suggest that
zinc status and maintenance of the renal ZnMT pool may play an important role in regulating
cadmium-induced renal
proteinuria and calcuria by preventing Cd2+ perturbation of the proximal tubule cell lysosome system.