GENTAMICIN NEPHROTOXICITY .2. PHYSIOLOGICAL, BIOCHEMICAL AND MORPHOLOGICAL EFFECTS OF PROLONGED ADMINISTRATION TO RATS

Abstract

The morphological, physiological and biochemical effects of gentamicin on the rat kidney following prolonged administration were studied. Sprague-Dawley and Fischer 344 strain rats were given 3, 10, 20 or 40 mg/kg body wt per day for 28 days. Morphologic alterations were evaluated by light microscopy and EM. Functional parameters included glomerular filtration rate, PAH [p-aminohippurate] secretion, renal plasma flow, Na reabsorption, K excretion, urine volume and protein and serum urea N. Oxidative metabolism of mitochondrial fractions from renal cortical homogenates was evaluated by O2 uptake and P:O ratios. The results indicate focal proximal tubular injury, decreased tubular maximum secretion of PAH and altered oxidative metabolism at the higher drug dose levels. Neither elevations of serum urea N nor alterations in glomerular filtration rate, renal plasma flow or Na or K excretion were observed. Apparently high dose levels (40 mg/kg per day) alter the structure and function of some proximal tubular segments when administered over prolonged periods. The alterations appear reversible. Although nephrotoxicity is identified under these conditions in rats, extrapolation to human patients usually receiving much lower doses must be guarded.