Aminoglycoside Nephrotoxicity

Aminoglycosides are life-saving antibiotics in patients with gram negative sepsis. Renal dysfunction occurs in approximately 10% of all clinical courses of aminoglycosides. Because of close pharmacokinetic and toxicologic similarities, rats are excellent human surrogates for comparing the nephrotoxic potentials of these antibiotics. Comparisons in rats are also more sensitive than clinical comparisons due to the insensitivities of clinical renal function tests, the confounding influences present in seriously-ill patients and the inability to make morphologic comparisons in the clinic. The pathogenesis of aminoglycoside nephrotoxicity is still evolving despite extensive world-wide investigations. However, these investigations have facilitated the identification of several inhibitors of aminoglycoside nephrotoxicity. The clinical usefulness of these inhibitors must still be established.