Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first 6 weeks of life

T Donge, Karel Allegaert, V Gotta, A Smits, E Levtchenko, D Mekahli, John van den Anker, M Pfister

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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 GA-adjusted 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.

Original languageEnglish
Pages (from-to)649-659
Number of pages11
JournalPediatric Nephrology
Issue number3
Publication statusPublished - 2021

Bibliographical note

Funding Information:
Open access funding provided by University of Basel. Tamara van Donge, Verena Gotta, John van den Anker, and Marc Pfister are funded by the Eckenstein-Geigy foundation. Elena Levtchenko is funded by F.W.O. Vlaanderen, grant 1801110N. The research activities of Anne Smits are supported by the Clinical Research and Education Council of the University Hospitals Leuven. Code availability

Publisher Copyright:
© 2020, The Author(s).

Research programs

  • EMC OR-01


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