Abstract
AIMS: Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. METHODS: We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of GFR(birth) (GFR at birth), and an Emax model dependent on PNA (with GFR(max), PNA(50) (PNA at which half of GFRmax is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. RESULT: In the GFR model, GFR(birth) varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for PNA(50), and current weight for GFR(max). The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. CONCLUSIONS: GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age.