OXYTETRACYCLINE-INDUCED NEPHROTOXICOSIS IN DOGS AFTER INTRAVENOUS ADMINISTRATION FOR EXPERIMENTAL BONE LABELING

Tetracyclines have been used as in vivo indicators of new bone formati on because they form complexes with mineral at bone-forming surfaces. Four of 12 dogs in a bone-labeling study developed clinical signs of r enal disease (vomiting, diarrhea, dehydration, and azotemia) within 1 to 2 days of receiving oxytetracycline at a bone-labeling dose of 25 m g/kg of body weight, once daily for 2 consecutive days. To delineate t he relationship between oxytetracycline administration and renal damag e, six dogs were given the bone-labeling dose intravenously and were s ubsequently evaluated by determination of clinical signs, serum bioche mical analysis, urinalysis, and histologic examination (experiment 1). Drug administration was modified in the five dogs remaining in the bo ne-labeling orthopedic study. These dogs received the oxytetracycline dose as a slow intravenous infusion diluted with 250 ml of lactated Ri nger's solution (experiment 2). All six dogs of experiment 1 developed persistent isosthenuria within 2 days of receiving the bone-labeling dose of oxytetracycline. Clinical illness (three of six dogs) was asso ciated with azotemia, creatinemia, and hyperphosphatemia. All dogs had multifocal, mild to moderate flattening of renal tubular epithelium, characteristic of nephrosis. None of the dogs of experiment 2 develope d any clinical indications of renal disease, and the only biochemical abnormality was isosthenuria in two of the five dogs, Thus the develop ment of clinical signs and biochemical abnormalities associated with t he intravenous administration of oxytetracycline was obviated by the s low administration of a dilution of the calculated bone-labeling dose of the antibiotic.