Single dose gentamicin nephrotoxicity in the dog: early functional and ultrastructural changes.

A single dose (15mg/kg) of the aminoglycoside antibiotic gentamicin was administered intravenously to 4 purebred 5-month old beagles. Six 24-hour creatinine, urea, phosphate, sodium, and potassium clearances were performed, three before and three after gentamicin infusions, as were hematology and urinalysis. Animals were necropsied on the fourth day after drug infusion. Renal clearances tended to decrease. Light microscopy revealed no significant renal lesions, but transmission electron microscopy demonstrated increased cytosomes with myeloid figures (cytosegresomes) in the proximal tubule cells of treated dogs. These structures are characteristic markers of gentamicin. therapy. In addition, the proximal tubules of treated dogs contained single membrane limited vesicles with granular proteinaceous material; a structure not previously reported to be associated with aminoglycoside nephrotoxicity. The significance and relationship of these vesicles to the pathogenesis of gentamicin toxic nephropathy is not known. This study suggests that a single moderate dose of gentamicin is nephrotoxic in the beagle as judged by functional and morphological criteria.