Enzymuria following amphotericin B application in the rat.

Area of Science:

• Nephrology
• Pharmacology
• Toxicology

Background:

• Amphotericin B is a critical antifungal agent with known nephrotoxic potential.
• Assessing early markers of renal injury is crucial for managing amphotericin B therapy.
• Urinary enzyme excretion can serve as a sensitive indicator of renal tubule damage.

Purpose of the Study:

• To investigate the effect of amphotericin B on urinary renal tubule enzyme excretion in rats.
• To determine if amphotericin B induces early signs of proximal renal tubule damage.
• To compare the effects of amphotericin B with sodium deoxycholate on renal enzyme excretion.

Main Methods:

• Rats were treated with amphotericin B (1.5 mg/kg b.i.d., i.v.) for 4 days.
• Urinary enzyme activity of N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (GRS), alanine-aminopeptidase (AAP), and gamma-glutamyltransferase (GGT) was measured daily.
• Creatinine clearance, fractional sodium, and potassium excretion were assessed.
• Control groups received saline or sodium deoxycholate.

Main Results:

• Amphotericin B significantly increased daily urinary excretion of NAG, GRS, AAP, and GGT compared to controls.
• Elevated enzyme excretion began after the first day of treatment and continued for 4 days.
• Creatinine clearance was significantly reduced in amphotericin B-treated rats (0.94 ml/min vs. 1.35 ml/min in controls).
• Sodium deoxycholate did not affect urinary renal tubular enzyme activity.

Conclusions:

• Amphotericin B administration induces early enzymuria, characterized by increased excretion of renal tubule enzymes.
• These findings suggest that amphotericin B causes damage to the proximal renal tubules.
• Urinary enzyme levels can serve as an early indicator of amphotericin B-induced nephrotoxicity.