Decreased fractional renal excretion of gentamicin in subtotal nephrectomized dogs

The purpose of this investigation was to determine the effects of subtotal surgical nephrectomy (three-quarters removal of renal mass) on the renal handling of gentamicin in the dog. Three and one-half months after surgery, dogs were anesthetized and steady-state clearances of gentamicin, creatinine, inulin and p-aminohippurate were determined. Subtotal nephrectomy proportionately decreased creatinine, inulin and p-aminohippurate clearances, but resulted in a significantly (P less than .05) decreased fractional excretion of gentamicin (0.97 +/- 0.24) (mean +/- S.D.) compared to intact dogs (1.22 +/- 0.08). Gentamicin serum protein binding by equilibrium dialysis was approximately 15% in both groups. In vitro canine cortical tissue slices accumulated drug as the slice/medium ratio was greater than one (1.77 +/- 0.47). This study indicates that the renal handling of gentamicin is altered in this disease model. This decreased fractional excretion of gentamicin implies that the quantity of drug excreted by the diseased kidney cannot be precisely predicted on the basis of glomerular filtration rate alone when drug dosage regimens are designed for patients with renal disease.