Enzymuria following amphotericin B application in the rat

The effect of amphotericin B application on urinary renal tubule enzyme excretion was investigated in rats treated with amphotericin B (1.5 mg kg-1 b.i.d., i.v.) for 4 days. Application of amphotericin B induced a significant higher daily urinary enzyme activity of the renal tubular enzymes N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (GRS), alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT) in comparison with controls and sodium deoxycholate treated animals as well. A significant increase in the renal excretion of NAG, GRS, AAP and GGT occurred after the first day of amphotericin B treatment and continued until the fourth day. Following treatment for 4 days with amphotericin B urine AAP activity amounted to 69 +/- 19 U g-1 creatinine, control: 39 +/- 7 U g-1 creatinine (P < 0.05). After 4 days GGT excretion increased to 803 +/- 238 U g-1 creatinine, control: 445 +/- 106 U g-1 creatinine (P < 0.05). At the fourth day NAG excretion was 80 +/- 39 U g-1 creatinine, control: 23 +/- 5 U g-1 creatinine (P < 0.05) and GRS 724 +/- 604 U g-1 creatinine (amphotericin B), control: 276 +/- 158 U g-1 creatinine (P < 0.05). Treatment with amphotericin B decreased the creatinine clearance significantly: 0.94 +/- 0.16 ml-1 min-1 vs. control 1.35 +/- 0.29 ml-1min-1 (P < 0.05). Fractional sodium and potassium excretion was not influenced by amphotericin B. The application of sodium deoxycholate had no influence on urinary renal tubular enzyme activity. The results show that amphotericin B application induces early enzymuria of renal tubule enzymes suggesting damage of proximal renal tubules.