The extent of nephrotoxicity for vancomycin remains controversial. In 1980s, vancomycin with a purity > 90% was available, and kidney toxicity defined by an increase in serum creatinine of at least 0.5 mg/dl, occurred in only about 5% of patients. However, dosing guidelines from the 1980s until 2008 recommended vancomycin trough concentrations between 5 and 15 μg/ml. Concern for treatment failures prompted recommendations for higher dosing (troughs 15 to 20 μg/ml) for serious infection, and acute kidney injury (AKI) rates attributable to the vancomycin increased.
Importantly, the risk of AKI increases with co-administration of other known nephrotoxins, in particular, aminoglycosides. Furthmore, the sort of infections treated with vancomycin may also cause AKI and sepsis is the most common cause of AKI in critically ill patients. Finally, studies in humans are mainly associations studies where the cause of AKI is usually multifacotorial.
Animal studies have demonstrated that higher doses and longer duration of vancomycin exposure correlates with increased histopathologic damage and elevations in urinary biomarkers of AKI.37-38 Damage is most prevalent at the proximal tubule, which is further supported by urinary biomarkers, such as kidney injury molecule-1 (KIM-1), clusterin, and osteopontin (OPN),
and in humans, insulin-like growth factor binding protein 7 (IGFBP7) as part of the nephrocheck test.
The mechanisms that underlie the pathogenesis of vancomycin nephrotoxicity are multifactorial but include interstitial nephritis, tubular injury due to oxidative stress, and cast formation.
Therapeutic drug monitoring can be used during vancomycin therapy to minimize the risk of nephrotoxicity associated with excessive drug exposure. Immunoassays are commonly utilized for measuring vancomycin levels.
In children, the concomitant administration of vancomycin and piperacillin/tazobactam has been associated with an elevated incidence of AKI, relative to other antibiotic regimens.