aminoglycoside nephrotoxicity

Epidemiology

• common cause of hospital-acquired acute renal failure
• risk increases with patient's age, volume-depletion & pre-existing renal disease
• relatively low mortality
• increases cost of hospitalization

Pathology

• aminoglycosides accumulate in proximal tubular epithelial cells
• oncosis of proximal tubular epithelial cells (ATN)
• reversible abnormalities herald nephrotoxicity
  • glycosuria
  • enzymuria
  • aminoaciduria
  • tubular proteinuria (beta-2 microglobulin)
• renal K+ & Mg+2 wasting, polyuria & nephrogenic diabetes insipidus may occur

Clinical manifestations

• generally manifests as non-oliguric acute tubular necrosis when the sole cause of renal dysfunction
• decreased GFR may not become apparent for 1-2 weeks

Laboratory

• urine Na+ is generally > 40 meq/L
• fractional excretion of Na+ (FENA) is > 1.5%

Management

• therapeutic levels of aminoglycosides should be monitored daily
• dosage should be adjusted for creatinine clearance
• discontinue aminoglycoside at 1st sign of nephrotoxicity

Additional terms

• acute tubular necrosis; tubulorrhexis (ATN)
• aminoglycoside antibiotic
• oncosis (ischemic cell death)