Aminoglycoside Nephrotoxicity in Humans

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Abstract
Aminoglycoside antibiotics are clearly nephrotoxic in humans, but since they are also highly efficacious in the treatment of serious infections caused by gram-negative bacteria, their nephrotoxicity must be viewed in perspective. Aminoglycosides cause both morphologic and functional alterations of the proximal renal tubules of humans. Although the proximal tubules appear to be affected in everyone who receives an aminoglycoside, most of the functions of the proximal tubule remain unimpaired. Exceptions include the proximal tubular reabsorption of β2-microglobulins and the renal excretion of several renal tubular enzymes. Glomerular dysfunction appears to arise subsequent to proximal tubular damage and the pathogenesis of the glomerular dysfunction remains an enigma. At a clinical level, aminoglycoside nephrotoxicity is infrequent, usually mild, and is probably always reversible if the aminoglycosides are used rationally. Variables that influence the incidence of nephrotoxicity include the dose and dosage regimen as well as the individual aminoglycoside chosen. In addition, host variables such as drug interactions, hypotension, and possibly other factors can influence nephrotoxicity. Viewed in perspective, aminoglycosides are valuable drugs that can be used relatively safely in humans.

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