Incidence and risk factors of acute kidney injury associated with continuous intravenous high-dose vancomycin in critically ill patients: A retrospective cohort study

Abstract

For vancomycin therapy of severe infections, the Infectious Diseases Society of America recommends high vancomycin trough levels, whose potential for inducing nephrotoxicity is controversial. We evaluated the incidence and risk factors of acute kidney injury (AKI) in critically ill patients given continuous intravenous vancomycin with target serum vancomycin levels of 20 to 30 mg/L.We retrospectively studied 107 continuous intravenous vancomycin treatments of ≥48 hours' duration with at least 2 serum vancomycin levels ≥20 mg/L in critically ill patients. Nephrotoxicity was defined according to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for AKI (ie, serum creatinine elevation by ≥26.5 μmoL/L or to ≥1.5 times baseline). Risk factors for AKI were identified by univariate and multivariate analyses.AKI developed in 31 (29%) courses. Higher serum vancomycin levels were associated with AKI (P < 0.01). Factors independently associated with AKI were highest serum vancomycin ≥40 mg/L (odds ratio [OR], 3.75; 95% confidence interval [CI], 1.40-10.37; P < 0.01), higher cumulative number of organ failures (OR, 2.63 95%CI, 1.42-5.31; P < 0.01), and cirrhosis of the liver (OR, 5.58; 95%CI, 1.08-31.59; P = 0.04).In this study, 29% of critically ill patients had AKI develop during continuous intravenous vancomycin therapy targeting serum levels of 20 to 30 mg/L. Serum vancomycin level ≥40 mg/L was independently associated with AKI.

Figure 1

Flowchart of the study. Acute kidney injury (AKI) defined as serum creatinine elevation by ≥26.5 μmol/L or to ≥1.5 times baseline.

Figure 2

Acute kidney injury (AKI) according to peak serum vancomycin level. The difference between the 2 groups was statistically significant (P < 0.01). AKI defined as serum creatinine elevation by ≥26.5 μmol/L or to ≥1.5 times baseline.

Figure 3

Boxplot of peak serum vancomycin (mg/L) according to stages of acute kidney injury (AKI). A boxplot is shown for each of the four each AKI stages. The X axis shows the 4 AKI stages (0–3) and the Y axis the peak serum vancomycin level (mg/L). The shaded box indicates the middle 50% of the data; the lower and upper ends of this box are the lowest and highest quartiles, respectively. The solid black horizontal line through each shaded box indicates the median value. The circles above the vertical solid black lines are individual outliers. The P value is for the overall comparison of peak serum vancomycin levels for each AKI stage. The AKI stages are defined in the Kidney Disease Improving Global Outcomes Clinical Practice Guideline,^[15] reported in Table 1.