EVIDENCE FOR LUMINAL UPTAKE OF GENTAMICIN IN THE PERFUSED RAT-KIDNEY

  • 1 January 1979
    • journal article
    • research article
    • Vol. 210  (2) , 247-251
Abstract
Gentamicin [an antibiotic] 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, filtering and non-filtering isolated perfused rat kidneys were studied. 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 h of perfusion. [14C]Cephaloridine accumulation was 38% greater in the non-filtering model. Gentamicin did not significantly change Na reabsorption or glomerular filtration rate during the 60-min study. Fractional K excretion was slightly but significantly increased by perfusion with gentamicin. Apparently, renal tubular gentamicin uptake is primarily by filtration and subsequent reabsorption, and the non-filtering and filtering isolated perfused rat kidney may be used to investigate mechanisms of renal accumulation of other nephrotoxic agents.