Tamara van Donge

Chapter 8 154 The aim of this study was to assess and quantify the effect of ibuprofen on serum creatinine profiles of ELBW neonates with various postnatal and gestational ages. This knowledge may support the interpretation of serum creatinine values in this neonatal subpopulation and inform clinicians on the kidney function and potential kidney injury in their patients. Method Ethics The studies involving human participants were reviewed and approved by the Ethics Committee UZ/KU Leuven (S63405, 17 June 2020). As this was a retrospective analysis of serum creatinine and clinical data, written consent from the legal guardians was not required to participate in this study in accordance with the national legislation and the institutional requirements. Serum creatinine dynamic model We applied a recently published dynamic model that characterized the serum creatinine concentrations for ELBW infants. 10 The model was developed based on 4026 serum creatinine concentrations collected during the first six weeks of life in 217 ELBW neonates. The median gestational age and birth weight was 27 weeks (26 – 28 weeks IQR) and 830 g (720 - 910 g IQR), respectively. The mode of delivery and gestational age showed an association with postnatal maturation of the creatinine clearance (faster clearance increase with advancing GA and after C-section). In this previous study, the elimination rate of creatinine (ket) was characterized as = !" !" #$ #$%& × ) *+,, ) -. *+,, / ) *+,, % &.( 0 "12 3 × +,-./0 (12) . Where t reflects postnatal age (days), CL BL reflects baseline creatinine clearance (L/day), emax is the maximum additional achieved clearance (L/day), t 50 corresponds to the time point where half of emax is achieved and the Hill coefficient describes the steepness of the creatinine-time relationship. Additional details on the dynamic model can be found in the original paper. 10 Ibuprofen treatment was included in the model on creatinine clearance at baseline (CL BL ) and accounted for a 5% decrease when ibuprofen was administered (CL BL i = 0.075 L/day × (1 + 2.55)). The study showed that ibuprofen treatment is associated with a decrease in creatinine clearance, whereas inotropic agents were not associated with changes in serum creatinine or creatinine clearance and therefore not included in the model. This study provided new insights on the perinatal factors (related to both physiology and pathophysiology) affecting serum creatinine and therefore influencing the