Aminoglycoside renal cortical kinetics: a clue to mechanisms of nephrotoxicity

In the presence of healthy renal tissues, aminoglycosides demonstrate important differences in quantitative renal cortical accumulation. These phenomena may correlate with clinical toxicity. Proximal tubular reabsorptive pathways appear to be of key significance in the production of high renal cortical drug concentrations. It appears that such drug transport can be blocked competitively. The presence of severe disease in renal tissues significantly influences the intrarenal distribution characteristics of antibiotics and is associated with reduced parenchymal concentration of all drugs, with the exception of doxycycline. Studies defining the intrarenal gradient characteristics of drugs provide us with a better understanding of factors of importance in appropriate antibiotic selection for the treatment of renal infections. The investigations also contribute to a better understanding of the mechanisms of antibiotic-induced nephrotoxicity and the potential clinical management by which such nephrotoxicity can be avoided. Study of the multiple physiologic and pathophysiologic factors that influence drug concentrations within the kidney should continue to provide us with information of both therapeutic and toxicologic value.