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Published on: February 2, 2021
A Large Cohort Study to Identify Risk Factors of Acute Kidney Injury in Pediatric Patients Undergoing Intravenous
Rahul K Goyal1, Brady S Moffett2,3, Kristine A Parbuoni1
1School of Pharmacy, University of Maryland Baltimore, Baltimore, Maryland, USA.
Insights
Clinical factors, not vancomycin levels, are key predictors of acute kidney injury (AKI) in children. Current dosing guidelines may not improve outcomes and require further study for optimal pediatric vancomycin therapy.
Area of Science:
- Pharmacology
- Nephrology
- Pediatric Medicine
Background:
- Acute kidney injury (AKI) is a concern in pediatric patients receiving vancomycin.
- The relative importance of vancomycin exposure versus clinical factors in AKI development is not well understood.
Purpose of the Study:
- To identify risk factors for AKI in pediatric patients on intravenous vancomycin.
- To assess the role of vancomycin concentrations in AKI.
- To evaluate the safety of recent (2020) vancomycin dosing guideline changes.
Main Methods:
- Retrospective cohort study using hospital data (2011-2019).
- Defined AKI using modified KDIGO criteria.
- Utilized population pharmacokinetic modeling and multivariate logistic regression to identify risk factors.
- Performed simulations to evaluate 2020 guideline recommendations.
Main Results:
- 18.9% of 1714 pediatric patients developed AKI.
- Independent risk factors for AKI included younger age, ICU stay, vasopressors, and certain concomitant antibiotics (piperacillin/tazobactam, amphotericin B).
- Vancomycin AUC showed a modest association with AKI, less predictive than clinical factors. Simulations suggested 2020 guidelines might slightly increase AKI incidence without clear benefit.
Conclusions:
- Clinical factors are more predictive of AKI than vancomycin exposure in pediatric patients.
- The clinical necessity of increased vancomycin dosing per 2020 guidelines is questionable due to low mortality rates and modest efficacy.
- Further prospective studies are needed to balance therapeutic benefits and nephrotoxicity risks for optimal pediatric vancomycin dosing.
Background And Objectives:
The relative contribution of vancomycin exposure versus clinical factors to acute kidney injury (AKI) development in pediatric patients remains unclear. This study examined risk factors for AKI in pediatric patients receiving intravenous vancomycin therapy, with particular focus on elucidating the role of vancomycin concentrations and evaluating the safety implications of recent dosing guideline changes published in 2020.
Methods:
For this retrospective cohort study, Texas Children's Hospital database was queried between 2011 and 2019 for demographics, concomitant medications, vancomycin dosing and levels, serum creatinine, and mortality. AKI was defined using modified KDIGO criteria. Empirical Bayesian forecasting with a published population pharmacokinetic (PK) model generated rich PK profiles from sparse sampling data. Multivariate logistic regression was used to identify risk factors, and simulations were performed to evaluate 2020 guideline recommendations.
Results:
The final analysis dataset included 2318 vancomycin courses in 1714 unique patients. The typical dosing regimen in our dataset was 45 mg/kg/day every 8 h. AKI occurred in 18.9% of patients. Independent risk factors included lower age, ICU residence, vasopressor administration, concurrent piperacillin/tazobactam, and amphotericin B use. While vancomycin 24-h area under the curve (AUC0-24) showed statistically significant association with AKI, the relationship was modest with minimal improvement in model performance compared to clinical factors alone. Simulations of 2020 guideline recommendations (60-80 mg/kg/day) predicted modest increases in AKI incidence from 19% to 21% when AUC was capped at 600 mg·h/L. However, given low mortality rate (1.9%) in our dataset despite only 43% of patients achieving the recommended AUC target of 400 mg·h/L, the clinical necessity for increased dosing remains questionable.
Conclusions:
Clinical factors are substantially more predictive of AKI than vancomycin exposure in pediatric patients. Given the questionable clinical necessity for increased dosing based on low mortality rates, prospective studies incorporating clinical efficacy endpoints are needed to establish optimal dosing strategies that balance therapeutic benefit with nephrotoxicity risk.
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