The survival of
breast cancer patients has significantly improved through the treatment with
anthracyclines. Although
anthracyclines are known to produce renal disease in experimental animals, little is known about the toxicity of
anthracyclines at clinically relevant doses in humans. In a previous study on
cancer patients we have observed an increase in the urinary activity of
N-acetyl-beta-D-glucosaminidase (NAG), an
indicator of renal tubular cell dysfunction that was accompanied by increased urinary
zinc loss. Because an increase in NAG activity was reported after the treatment with
anthracyclines, we hypothesized that an increase in urinary NAG activity in
breast cancer patients treated with
anthracycline-based regimens will be accompanied by hyperzincuria and hypozincemia. Urinary and serum
zinc, urinary NAG and serum
creatinine were examined during
chemotherapy in 26
breast cancer patients treated with
anthracycline-based
chemotherapy. A trend for increased NAG activity, as compared to baseline, was observed throughout the first 4 cycles of treatment. NAG activity was significantly elevated compared to pretreatment levels one week after the first, third and fourth dose of
chemotherapy. Serum
creatinine concentrations decreased significantly after the second cycle of
therapy. On the other hand, urinary and serum
zinc levels did not change significantly during the treatment. In conclusion, our data confirm the presence of mild renal tubular cell dysfunction in
breast cancer patients treated with
doxorubicin-based
chemotherapy. Increased urinary NAG is accompanied by a decrease in serum
creatinine which is consistent with hyperfiltration. These changes are not associated with abnormalities of renal
zinc handling or a decrease in serum
zinc concentrations.