Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium-polluted rice for 22 months

To determine whether low-dose oral administration of cadmium (Cd) induces r enal toxicity, six groups of female Sprague-Dawley rats were fed a diet con taining low amounts of CdCl2 or Cd-polluted rice at concentrations up to 40 ppm, and were killed after 12, 18, and 22 months (experiment 1). In additi on to the determination of cortical Cd levels and histopathological assessm ent of kidneys, labeling indices (LIs) for proliferating cell nuclear antig en (PCNA) in the renal cortical tubular epithelium of Cd-treated rats were determined as a measure of regenerative activity. For comparison, the kidne ys of rats given diets containing small to large amounts of CdCl2 up to 600 ppm for 4 months were similarly examined (experiment 2). Animals in experi ment 1 demonstrated spontaneous chronic nephropathy and fluctuation in the tubular PCNA LI, but these findings were not correlated with renal Cd level s at 22 months. PCNA LI on the other hand, appeared to be linked to the sev erity of chronic nephropathy. In experiment 2, levels of CdCl2 of 200 ppm o r more clearly induced degeneration and apoptosis of proximal tubules with high correlations between renal Cd levels, PCNA LI, and the severity of tub ular degeneration. The results demonstrated that, in contrast to high-dose Cd administration, treatment with 40 ppm or less for 22 months did not infl uence tubular regeneration as a component of nonspecific chronic nephropath y, suggesting that long-term oral administration of low levels of Cd does n ot injure renal tubules in female rats.