Renal handling of gentamicin by normal and ischemic canine kidneys

The purpose of this study was to examine the pharmacokinetics of gentamicin renal uptake in dogs and assess the role of chronic renal ischemia. A stenosing silver clip was placed on the left renal artery of four mongrel dogs. Six months later, each dog received an infusion of gentamicin and inulin. Blood and urine samples were collected serially. In each dog, the ischemic left kidney was smaller and had a lower RPF and C_cr. The decrease in C_cr was highly correlated with the decrease in RPF. Measured gentamicin kidney concentrations were found to be in good agreement with predicted values based on the amount reabsorbed and the kidney weight. Within each animal (control vs. ischemic kidney), there was a significant correlation between the filtered load of gentamicin and both the renal reabsorption and excretion of gentamicin. These relationships exhibited high r² values, demonstrating that the induced ischemia did not alter the filtration or reabsorbtive mechanisms of gentamicin within the animal, but only decreased the filtered load. Between animals, gentamicin excretion was proportional to filtered load, but gentamicin reabsorption had the lowest r² value, explaining only 49% of the observed variance. The unexplained variance encountered in gentamicin reabsorption between animals establishes that there are important determinants of renal tissue concentration that are independent of filtration or filtered load. This study suggests that a reduction in glomerular filtration is not an important risk factor for elevated gentamicin renal tissue concentrations, provided that serum concentrations are controlled within the therapeutic range.