Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the f
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ORIGINAL ARTICLE
Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first 6 weeks of life Tamara van Donge 1 & Karel Allegaert 2,3,4 & Verena Gotta 1 & Anne Smits 2,5 & Elena Levtchenko 2,6 & Djalila Mekahli 2,6 & John van den Anker 1,7,8 & Marc Pfister 1 Received: 24 April 2020 / Revised: 23 July 2020 / Accepted: 27 August 2020 # The Author(s) 2020
Abstract Background Characterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging. Methods We performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling. Key covariates such as gestational age (GA), mode of delivery (MOD), and treatment with ibuprofen or inotropic agents were investigated. Results A total of 2814 Scr concentrations were analyzed. GA was associated with Scr at birth (higher with advancing GA), and GA and MOD showed an association with postnatal maturation of CLcr (faster clearance increase with advancing GA and after C-section). Small CLcr decrease (≤ 5%) was quantified during ibuprofen treatment. For a GA of 27 weeks, mean Scr (estimated CLcr) at birth was 0.61 mg/dl (0.23 ml/min), increasing to 0.87 mg/dl (0.27 ml/min) at day three, and decreasing to 0.36 mg/dl (0.67 ml/min) at day 42 after birth. Conclusions We report the first mathematical model able to characterize Scr and CLcr in ELBW neonates during the first 6 weeks of life in a quantitative manner as a function of GA, MOD, and ibuprofen treatment. This model allows the derivation of GAadjusted reference ranges for ELBW neonates and provides a rationale for normative Scr concentrations, and as such will help clinicians to further optimize monitoring and treatment decisions in this vulnerable patient population. Keywords Reference ranges . Glomerular filtration rate . Creatinine reabsorption . ELBW neonates . Model-based simulations
Abbreviations BSA Body surface area CLBL Baseline creatinine clearance
creabirth ELBW GA
Creatinine concentration at birth Extremely low birth weight Gestational age
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00467-020-04749-3) contains supplementary material, which is available to authorized users. * Tamara van Donge [email protected] 1
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Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, Basel, Switzerland Department of Development and Regeneration, KU Leuven, Leuven, Belgium Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
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Department of Clinical Pharmacy, Erasmus MC, Rotterdam, The Netherlands
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Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
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Department of Pediatric Neph
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