Risk factors for vancomycin nephrotoxicity
Onset / Magnitude
The onset of vancomycin nephrotoxicity typically ranges from four to
eight days from the start of therapy. The degree of vancomycin-induced
renal dysfunction is modest, with a typical decrease of 35-45% in
creatinine clearance from baseline.
The use of concomitant nephrotoxins is a significant risk factor for
development of nephrotoxicity.
Furosemide is not a direct nephrotoxin, but its use may cause
dehydration, which further increases the risk of developing
nephrotoxicity. One study showed that a loop diuretic was present in
63% of adult patients who had nephrotoxicity during vancomycin therapy
as compared with 44% with no renal toxicity.
Obesity was seen to be a significant predictor for occurrence and time
of development of nephrotoxicity. It is postulated that the volume of
distribution in the central compartment does not increase
proportionally with weight and thus accounts for the higher trough
values observed among obese patients.
Nephrotoxicity occurred in 9-21% of patients on high-dose therapy
compared with 2% in patients on standard-dose therapy in the absence
of concomitant risk factors for nephrotoxicity.
Duration of therapy
Prabaker et al. observed that the rate of nephrotoxicity increased
from 12 to 22% beyond ten days of therapy. Jeffres et al. observed an
odds ratio of 2.55 for nephrotoxicity after >= 14 days of treatment.
In another study, Hidayat et al. found that the risk appeared to
increase incrementally as the treatment was prolonged in patients who
achieved high trough levels (15 to 20 mcg/ml): 6% for >=7 days, 21%
for 8 to 14 days and 30% for >14 days.
A recent two-phase retrospective analysis identified vancomycin serum
trough concentrations >= 14 mcg/ml, duration of vancomycin therapy >=
7 days, and baseline SCR levels >= 1.7 mg/dl as independent predictors
A high APACHE II score, ICU stay, and receipt of vasopressor agents
appear to be significant risk factors for the development of nephrotoxicity.
Lodise et al. observed that ICU patients have a higher baseline risk
for development of nephrotoxicity than non-ICU patients at a lower trough
concentration threshold: >20% probability of nephrotoxicity at a trough >10
mcg/ml in ICU patients versus trough >20 mcg/ml in non-ICU patients.
Long term outcome
There is no evidence that acute vancomycin nephrotoxicity leads to
chronic kidney damage.
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