Pathogenesis of nephrotoxicity of cephalosporins and aminoglycosides: a review of current concepts.

Third-generation cephalosporins promise to replace combinations containing aminoglycosides as safer, broad-spectrum antibiotic therapy. First, however, the possibility of nephrotoxicity as demonstrated with cephaloridine, must be excluded. For this reason, we must understand more about how cephalosporins and aminoglycosides damage the kidneys. Aminoglycosides accumulate in the renal lysosomes and may interfere with Na+-, K+-dependent adenosine triphosphatase activity. Experiments with cephaloridine and cephaloglycin, two nephrotoxic cephalosporins, indicate that they cause mitochondrial injury that leads to impaired cellular respiration. Results of experiments on the effects of treatments that combine cephalosporin with aminoglycosides or other drugs are confusing because inappropriate experimental models were used. Use of insensitive animals, administration of diuretics without prior induction of tubule damage, and insufficient dosages of drugs all cloud the interpretation of results. The standards for animal studies of cephalosporin nephrotoxicity should be revised to make them more relevant to humans.