Furosemide enhancement of experimental gentamicin nephrotoxicity: comparison of functional and morphological changes with activities of urinary enzymes.

Dogs were given gentamicin (10 mg/kg) intramuscularly every 8 hr for 10 days. Levels of serum creatinine rose by day 6 (0.91 +/- 0.08 vs. 0.75 +/- 0.02 mg/dl for controls, P less than 0.05) and of blood urea nitrogen by day 8 (24.3 +/- 4.80 vs. 16.1 +/- 0.90 mg/dl for controls, P less than 0.05). Gentamicin nephrotoxicity occurred earlier and was more marked when furosemide (2 mg/kg) was added: the level of serum creatinine by day 6 was 1.62 +/- 0.25 mg/dl (P less than 0.05), and the level of blood urea nitrogen by day 8 was 181 +/- 23.5 mg/dl (P less than 0.01). Elevations in the activities of the urinary enzymes beta-glucuronidase, N-acetyl-beta-glucosaminidase, and muramidase preceded rises in levels of serum creatinine and blood urea nitrogen. Examination of serial percutaneous renal biopsy specimens showed that gentamicin administration was associated with hyaline droplet degeneration, lysosomal changes, and, later, cell necrosis (primarily of the proximal tubules). Changes in renal morphology were more severe and occurred earlier when furosemide was administered concomitantly. In summary, furosemide enhanced gentamicin nephrotoxicity. Enzymuria was an early sign of gentamicin nephrotoxicity.