Relationship between the nephrotoxicity and ototoxicity induced by gentamicin in the guinea pig

Guinea pigs were treated with daily single subcutaneous injections of 60 mg gentamicin per kg for 3 weeks. Renal, cochlear and vestibular functions were monitored before, during and after treatment. The degree and onset of gentamicin oto- and nephrotoxocity differed during the treatment period. Alterations to the kidney functions were observed from the first week while the onset of ototoxicity occurred later, at the third and fourth week for the cochlear and vestibular functions respectively. Moreover, when treatment ended, renal function demonstrated signs of recovery, while auditory and vestibular function continued to worsen. Deficits in cochlear function and structural changes (missing outer hair cells) correlated with gentamicin serum concentrations, while vestibular alterations (loss in nystagmic reactions) did not. No distinct relationship could be established between auditory and vestibular loss and the renal parameters monitored. The results suggest that gentamicin-induced nephro- and oto-toxicity are dissociated phenomena and that cochleotoxicity was dependent on aminoglycoside serum level.