Aminoglycoside nephrotoxicity: a double blind prospective randomized study of gentamicin and tobramycin

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Abstract
Patients receiving gentamicin (25) or tobramycin (29) were evaluated in a randomized, prospective, double-blind study. Sequential serum samples for creatinine determination and urine samples for urinalysis, β-2-microglobulin, and N-acetyl-glucosaminidase assays were obtained to assess the frequency of nephrotoxicity and to evaluate measures possibly predicting impaired renal function. Each aminoglycoside induced measurable decrements in renal function. Although the mean total dose per kg and mean serum trough levels were slightly higher in the tobramycin group, there was a trend towards greater toxicity in those receiving gentamicin, whether measured as a mean increase in serum creatinine during therapy, as an elevation of 0·3 mg/dl or more in serum creatinine, or as at least a doubling of the serum creatinine. Adjusted for the dose or the serum trough level of aminoglycoside, increments in serum creatinine concentration were observed more often with gentamicin. The differences were minor and their clinical significance remains unestablished. The development of casts correlated with nephrotoxicity, but the remaining parameters were not helpful as predictors of renal functional impairment. Each aminoglycoside must be used cautiously, following previous guidelines, to lessen the incidence of toxicity. Dosage should be decreased when urinary casts appear.