Combination chemotherapy and renal enzyme and protein excretion in patients with breast cancer

This study investigated the effect of doxorubicin-based chemotherapy on the kidney, as assessed by enzymuria, proteinuria and albuminuria in patients with breast cancer. Nine patients with breast cancer received primary (neo-adjuvant) chemotherapy - intravenous doxorubicin (50 mg/m 2 ), vincristine (1.2 mg/m 2 ), cyclophosphamide (1 g/m 2 ) and oral prednisolone (40 mg/day for 5 days) and venous blood and urine samples were taken before treatment and on days 1,10 and 20, after chemotherapy (Pulse 1). This regime was then repeated (Pulse 2). Urine activities of gamma-glutamyl-transferase (GGT), alanine aminopeptidase and N-acetyl-β-D-glucosaminidase (NAG), and proteinuria and albuminuria were measured. After initiation of the first pulse of chemotherapy, significantly increased NAG and GGT enzymuria were noted on days 1 and 20, while increased proteinuria was present only on day 1. Following the second pulse of chemotherapy increased proteinuria was observed on days 1 and 10. Creatinine clearance rates remained unaltered throughout. A group of six healthy age- and sex-matched controls, with no known renal disease, were also studied and enzymuria, proteinuria and creatinine clearance rates were not significantly altered over the experimental period. This study indicates that chemotherapy produces a moderate renal insult as manifested by increased NAG enzymuria and proteinuria without affecting overall renal function. The results suggest that renal function should be monitored in patients undergoing repeated cycles of chemotherapy, especially if there has been combinations with, or previous exposure to, chemotherapeutic agents with known nephrotoxic potential.