Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients

Pediatr Crit Care Med. 2017 Sep;18(9):e388-e394. doi: 10.1097/PCC.0000000000001228.


Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault.

Design: Retrospective, two-center, cohort study from 2003 to 2016.

Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals.

Patients: Children from 1 to 21 years old.

Interventions: None.

Measurements and main results: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 µg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R = 0.083).

Conclusions: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / pharmacokinetics*
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Creatinine / metabolism
  • Critical Care
  • Critical Illness*
  • Drug Monitoring
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Infant
  • Linear Models
  • Male
  • Metabolic Clearance Rate
  • Models, Theoretical*
  • Retrospective Studies
  • Vancomycin / pharmacokinetics*
  • Young Adult


  • Anti-Bacterial Agents
  • Biomarkers
  • Vancomycin
  • Creatinine