Effect of osmotic diuresis on gentamicin-induced nephrotoxicity in rats

The effect of isosorbide diuresis on gentamicin excretion and tissue accumulation as well as gentamicin-induced histopathologic changes in renal tissue were examined in rats. Gentamicin (30, 60, 120, 160 mg/kg) was administered s.c. for 10 consecutive days with or without isosorbide pretreatment. Osmotic diuresis with isosorbide did not significantly reduce the dose-dependent extent of gentamicin accumulation in renal tissues in comparison to nondiuresed rats. Although the urinary concentration of gentamicin was reduced in the diuresed animals, total gentamicin excretion remained unaffected. In addition, diuresis altered neither the renal excretion of the proximal tubular cell marker enzyme, N-acetyl-B-glucosaminidase, nor the severity of pathologic damage as determined by light microscopic examination of renal tissues. It appears that osmotically-induced diuresis alone is insufficient to prevent or significantly reduce gentamicin nephrotoxicity in rats. This is in contrast to other forms of diuretic therapy, such as furosemide, which have been shown to effectively reduce renal accumulation and resultant renal toxicity of aminoglycoside administration.