Renal Function Descriptors in Neonates: Which Creatinine‐Based Equation Best Describes Vancomycin Clearance?

BACKGROUND: Glomerular function develops rapidly in the first month of life. Several estimated glomerular filtration rate (eGFR) equations have been applied to estimate the rate of clearance (CL) of renally-excreted drugs. This study aimed to compare eGFR with reference values and analyze their influence on vancomycin CL. Data were collected for neonates (3-30 days postnatal age; PNA) with ≥ 1 vancomycin serum concentration(s). Complete data could not be analyzed before September 8, 2014. A population PK model was constructed using NONMEM 7.2. eGFR was calculated using creatinine (Cr)-based equations from modified Schwartz (1), Leger (2), Pottel (3), and British Columbia’s Children’s Hospital (4) equations. Reference eGFR values were derived from Cr. RESULTS: A total of 528 neonates contributed vancomycin 6121 concentrations. The median gestational age (GA) was 29 (IQR 25-36) weeks. Schwartz equation provided comparable results with reference values in preterm neonates, i.e. 24.4 (20.6-26.6) mL/min/1.73 m2 at 14 days PNA in 29 weeks GA infants. In contrast, elevated eGFR were obtained: 46.7+/- 18.2 (2) 52.8 +/- (3), and 44.9 +/-17.6 (4) mL/min/1.7 m2. Theser were close to the values using equations based on cystatin C. Vancomycin PK was analyzed using a one-compartment model with first-order elimination. Weight, postmenstrual age, and eGFR were significant covariated for CL. Between-subject variability decreased by 38.3% with the inclusion of eGRF alone. Although Schwartz equation contributed the best fit, estimated CL (0.13 =/- 0.1 L/hr/kg) across eGRF equations were in reasonable agreement with literature values. Conclusion: Inclusion of eGFR can be used to estimate vancomycin C. The modified Schwartz equation was the best predictor of vancomycin CL in this neonatal population.