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Updated: Oct 2, 2025
Transdermal Measurement of Glomerular Filtration Rate in Mechanically Ventilated Piglets
Published on: September 13, 2022
Prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin
Yunjiao Wu1, Karel Allegaert2,3, Robert B Flint2,4
1Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Insights
Glomerular filtration rate (GFR) maturation in neonates is crucial for drug dosing. This study developed an optimized model showing GFR depends on birth weight, postnatal age, and gestational age for accurate predictions.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Neonatal Physiology
- Drug Development
Background:
- Accurate glomerular filtration rate (GFR) estimation is vital for predicting drug clearance in neonates and infants.
- Existing GFR maturation models require refinement to account for the heterogeneity in preterm and term infants.
Purpose of the Study:
- To describe GFR maturation in neonates and young infants (postnatal age < 90 days).
- To evaluate and optimize existing GFR maturation models using individual inulin clearance data.
- To develop a refined model for predicting GFR in this population.
Main Methods:
- Evaluation of seven published GFR maturation models against 381 individual inulin clearance (CL_inulin) datasets.
- Optimization of the best-performing model using NONMEM V7.4.3 software.
- Analysis of subject data including birth weight, gestational age, current weight, postnatal age, and CL_inulin.
Main Results:
- The De Cock 2014 model, incorporating birth weight and postnatal age, demonstrated the best predictive performance.
- The optimized model revealed that GFR at birth is primarily influenced by birth weight.
- Postnatal GFR maturation is dependent on postnatal age and gestational age, with higher gestational age correlating with faster maturation.
Conclusions:
- Neonatal GFR models must differentiate between prenatal maturation (linked to birth weight) and postnatal maturation.
- An optimized model was developed, demonstrating that postnatal GFR maturation in neonates and infants is dependent on postnatal age and gestational age.
- This refined model improves the prediction of GFR maturation in preterm and term neonates and young infants.
Abstract:
Describing glomerular filtration rate (GFR) maturation across the heterogeneous population of preterm and term neonates and infants is important to predict the clearance of renally cleared drugs. This study aims to describe the GFR maturation in (pre)term neonates and young infants (PNA < 90 days) using individual inulin clearance data (CLinulin). To this end, published GFR maturation models were evaluated by comparing their predicted GFR with CLinulin retrieved from literature. The best model was subsequently optimized in NONMEM V7.4.3 to better fit the CLinulin values. Our study evaluated seven models and collected 381 individual CLinulin values from 333 subjects with median (range) birthweight (BWb) 1880 g (580-4950), gestational age (GA) 34 weeks (25-43), current weight (CW) 1890 g (480-6200), postnatal age (PNA) 3 days (0-75), and CLinulin 2.20 ml/min (0.43-17.90). The De Cock 2014 model (covariates: BWb and PNA) performed the best in predicting CLinulin, followed by the Rhodin 2009 model (covariates: CW and postmenstrual age). The final optimized model shows that GFR at birth is determined by BWb, thereafter the maturation rate of GFR is dependent on PNA and GA, with a higher GA showing an overall faster maturation. To conclude, using individual CLinulin data, we found that a model for neonatal GFR requires a distinction between prenatal maturation quantified by BWb and postnatal maturation. To capture postnatal GFR maturation in (pre)term neonates and young infants, we developed an optimized model in which PNA-related maturation was dependent on GA.
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