Background Serum creatinine (SCr) is used as a surrogate marker of glomerular filtration rate to guide dosing of drugs eliminated by the kidney. Serum Cystatin C (S-CysC) has been suggested as a more reliable biomarker than SCr for monitoring kidney function in adults and children. Purpose of this study was to evaluate whether S-CysC is a more useful marker for estimating vancomycin clearance in neonates and young infants.

Methods Pharmacokinetic (PK), Scr and S-CysC data were collected in patients undergoing continuous intravenous vancomycin treatment in the neonatal intensive care unit of Robert Debré Hospital - Paris. A population PK analysis was performed with the software package NONMEM, utilizing vancomycin therapeutic drug monitoring samples. S-CysC and SCr were compared in terms of usefulness to explain inter-individual variability (IIV) of vancomycin clearance. Statistical criteria were used for covariate selection.

Results A total of 58 concentrations from 47 patients (gestational age [GA] ranging from 23 to 41 weeks and postmenstrual age [PMA] ranging from 26 to 46 weeks) were modeled with an allometric one-compartment model with first-order elimination. The median (range) values for SCr and S-CysC were 41.5 (12.0 to 102.0) µmol/L and 1.38 (0.95 to 2.32) mg/L, respectively. When tested individually, SCr and S-CysC explained 26.4% and 9.8% of IIV of vancomycin clearance, respectively. PMA was superior as a covariate on clearance, over the combination of GA and postnatal age. As such, bodyweight, PMA, and SCr were retained as significant covariates on clearance in the final model.

Conclusions Serum Creatinine was found to be more useful than Serum Cystatin C to explain IIV of vancomycin clearance in this population. Further studies are needed to evaluate the utility of renal biomarkers to predict clearance and dosing of renally eliminated drugs in neonates.

Disclosure(s) Nothing to disclose