Evidence for luminal uptake of gentamicin in the perfused rat kidney

Gentamicin nephrotoxicity is preceded by proximal tubular accumulation of the drug. To determine whether gentamicin enters cells from the peritubular surface or from the tubular lumen after filtration, we studied filtering and non-filtering isolated perfused rat kidneys. Filtering kidneys were perfused with 6 g/dl of albumin, non-filtering kidneys with 11 g/dl of albumin and a lower perfusion pressure after ureteral occlusion. Accumulation of [14C]gentamicin in filtering or non-filtering kidneys was compared to that of [14C]cephaloridine, which is taken up primarily at the antiluminal cell surface. Renal accumulation of gentamicin was approximately 4 times greater in filtering than in non-filtering kidneys after 1 hr of perfusion. In contrast, accumulation of [14C]cephaloridine was 38% greater in the non-filtering model. Gentamicin did not significantly change sodium reabsorption or glomerular filtration rate during the 60-min study. Fractional potassium excretion, however, was slightly but significantly increased by perfusion with gentamicin. Our results indicate that 1) renal tubular gentamicin uptake is primarily by filtration and subsequent reabsorption and 2) the non-filtering and filtering isolated perfused rat kidney may be used to investigate mechanisms of renal accumulation of other nephrotoxic agents.