Aminoglycoside nephrotoxicity: pathogenesis and prevention

Nephrotoxicity resulting from aminoglycoside antibiotics is a serious clinical problem and the incidence is probably increasing. The mechanism of renal toxicity is unclear but these agents affect several nephron functions including glomerular filtration, proximal tubular reabsorption, and urinary concentration. The degree of toxicity appears to correlate with the level of renal tissue concentration of the aminoglycoside. Clinical nephrotoxicity is most likely to occur in the presence of volume depletion, advancing age, preexisting renal dysfunction and exposure to other nephrotoxins. Despite the use of dosing nomograms, nephrotoxicity still occurs in some patients and the decline in renal function may only become apparent after completion of the antibiotic course. Subclinical nephrotoxic effects from aminoglycosides probably occur in all patients treated with these agents and only the most severely affected have clinically apparent nephrotoxicity.