Manifestations of and risk factors for aminoglycoside nephrotoxicity
- Brian S Decker, MD, PharmD
Brian S Decker, MD, PharmD
- Assistant Professor of Clinical Medicine
- Indiana University Department of Medicine
- Bruce A Molitoris, MD
Bruce A Molitoris, MD
- Professor of Medicine
- Indiana University School of Medicine
Acute kidney injury is a relatively common complication of therapy with the aminoglycoside antibiotics, with a rise in the plasma creatinine concentration of more than 0.5 to 1 mg/dL (44 to 88 micromol/L) or 50 percent increase in plasma creatinine concentration from baseline occurring in 10 to 20 percent of patients [1-4].
Aminoglycosides are freely filtered across the glomerulus and then partially taken up by, concentrated in, and produce damage to proximal tubular cells. The renal injury induced by these drugs is related to their preferential accumulation in the renal cortex. After administration, up to 5 to 10 percent of the parenteral dose is retained in the renal cortex, where it can achieve concentrations greatly exceeding the concurrent serum concentration . This preferential sequestration of aminoglycosides in proximal tubule cells accounts for the observation that renal failure may become clinically apparent as late as several days after the drug has been discontinued. (See "Pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity".)
The manifestations of and risk factors for aminoglycoside nephrotoxicity are reviewed here. Acute tubular necrosis due to ischemia or other insults and the pathogenesis and potential therapy of aminoglycoside nephrotoxicity are discussed separately. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults" and "Pathogenesis and etiology of ischemic acute tubular necrosis" and "Pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity".)
Nonoliguric acute kidney injury — Acute kidney injury from aminoglycoside exposure typically manifests after five to seven days of therapy. The nonoliguric aspect of the renal failure is secondary to a loss in renal concentrating ability believed to be the result of distal tubular damage.
The acute tubular necrosis that occurs from aminoglycoside exposure is rarely severe, with incremental increases in the plasma creatinine that are usually mild (0.5 to 2.0 mg/dL [44 to 177 micromol/liter]) . However, aminoglycosides can result in toxicity, mandating renal replacement therapy in patients who already have chronic kidney disease (CKD). The urine sediment most commonly shows mild proteinuria, hyaline, and granular casts. The fractional excretion of sodium is generally above 1 percent (calculator 1) or, for standard units, (calculator 2). (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury (acute renal failure)".)
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- Nonoliguric acute kidney injury
- Distal tubular dysfunction
- Electrolyte abnormalities
- RISK FACTORS
- Prolonged duration of therapy
- Advanced age
- Comorbid disease
- Reduced effective volume
- Concomitant medications
- Elevated plasma drug concentrations
- Type of aminoglycoside
- Frequency of dosing