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Vancomycin-Induced Acute Kidney Injury in Intensive Care Patients: A Target Trial Emulation Study Using Multicenter
Izak A R Yasrebi-de Kom1,2, Kitty J Jager1,2, Vianda S Stel1,2
1Department of Medical Informatics, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Purpose:
The potential of vancomycin to cause acute kidney injury (AKI) in adult intensive care patients is subject to debate due to suboptimal designs of past studies. Therefore, we aimed to estimate the effect of initiating vancomycin versus one of several minimally nephrotoxic alternative antibiotics on the 14-day risk of AKI using the target trial emulation framework.
Methods:
A hypothetical trial was emulated using routinely collected data from 15 Dutch intensive care units (ICUs) spanning 2010-2019. We used an active comparator control group with the following alternative antibiotics: clindamycin, linezolid, teicoplanin, meropenem, cefazolin, and daptomycin. AKI was diagnosed according to the KDIGO serum creatinine (SCr) criteria. Cumulative incidence curves were estimated using the Aalen-Johansen method and adjusted for confounding and selection bias through inverse probability of treatment and censoring weighting. Given the time lag of 24-48 h between changes in renal function and SCr, we summarized the estimates by calculating the absolute risks and risk differences at both 2 and 14 days after initiation.
Results:
We included 1809 ICU admissions. After adjustment, vancomycin was associated with a higher risk of AKI at 14 days of follow-up compared to the alternative antibiotics (0.28 [95% confidence interval (CI) 0.21-0.34] vs. 0.17 [95% CI 0.14-0.20]; risk difference 0.11 [95% CI 0.04-0.19]), but not at 2 days of follow-up (0.10 [95% CI 0.06-0.12] vs. 0.10 [95% CI 0.08-0.11]; risk difference 0.00 [95% CI -0.03-0.03]).
Conclusions:
Our findings indicate that vancomycin causes a higher risk of AKI compared to the alternative antibiotics. We recommend clinicians to be compliant with vancomycin-induced AKI prevention strategies, such as therapeutic drug monitoring or the consideration of an alternative antibiotic if possible.
Insights
Vancomycin increases the risk of acute kidney injury (AKI) in intensive care unit (ICU) patients by 14 days compared to alternative antibiotics. Clinicians should consider prevention strategies and alternative treatments when possible.
Area of Science:
- Nephrology
- Critical Care Medicine
- Pharmacology
Background:
- The nephrotoxicity of vancomycin in adult intensive care patients is debated due to prior study limitations.
- Target trial emulation offers a robust framework to assess drug-induced adverse events.
Purpose of the Study:
- To estimate the 14-day risk of acute kidney injury (AKI) associated with vancomycin initiation versus alternative antibiotics in ICU patients.
- To address the controversy surrounding vancomycin's nephrotoxic potential using a rigorous emulation method.
Main Methods:
- A target trial was emulated using routinely collected data from 15 Dutch ICUs (2010-2019).
- Vancomycin was compared against a panel of minimally nephrotoxic antibiotics (clindamycin, linezolid, teicoplanin, meropenem, cefazolin, daptomycin).
- Acute kidney injury (AKI) was defined by KDIGO serum creatinine criteria, with confounding adjusted via inverse probability weighting.
Main Results:
- In 1809 ICU admissions, vancomycin was linked to a higher 14-day AKI risk (28% vs. 17%; risk difference 11%).
- No significant difference in AKI risk was observed at 2 days (10% vs. 10%; risk difference 0%).
Conclusions:
- Vancomycin use is associated with an increased risk of AKI in ICU patients compared to alternative antibiotics.
- Implementing vancomycin-induced AKI prevention strategies, including therapeutic drug monitoring and considering alternatives, is recommended.
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