Tamara van Donge

Chapter 7 136 Discussion This is the first study that provides reference ranges for real world Scr concentrations and associated creatinine clearance for ELBW neonates by characterizing the dynamics of Scr concentrations during the first six weeks of life in a quantitative manner by means of a mathematical model. GA, MOD and ibuprofen treatment were key factors influencing individual creatinine profiles and corresponding creatinine clearance, while prenatal lung maturation and the need for treatment with inotropic agents were no significant covariates. There are several aspects that require further interpretation and context. First, in 2002, Léger et al. have applied population pharmacokinetic approaches to pediatric creatinine data with the aim of characterizing GFR. Their population comprised of children with a mean age of 11 years, making the results not translatable to our preterm neonatal population. 7 Vieux et al. obtained GFR reference values retrieved from regression models based on Scr assessments in plasma and urine on day 7, 14, 21 and 28 of life. 4 Their assessment of median GFR for a 27-week-old neonate on day 14 after birth was higher as compared to our calculations (16.22 ml/min/1.73m 2 vs 9.40 ml/min/1.73m 2 , Table 4). This difference might be explained by the fact that our population was considered more immature (smaller GA and lower birthweight) and different equations were applied for the calculation of individual BSA (Dubois and Dubois versus Ahn). 16,18 In the current study, BSA was calculated based on current weight measurements, reflecting an accurate image of postnatal development. Furthermore, it is well known that bilirubin is one of the most relevant interfering compounds when creatinine is measured. As bilirubin is mainly an issue in early neonatal life, and subsequently disappears, this also indicates that creatinine decrease in absolute values will be more pronounced over the first week(s) of neonatal life, suggested to reflect a higher creatinine clearance. Additionally, different assays were used for the Scr quantification (Jaffe versus enzymatic). 4,11 It has been previously shown that Jaffe Scr concentrations were significantly and systematically higher (difference 0.1-0.2 mg/ dl) compared to the enzymatic quantification throughout postnatal life. 19 Along the same line, there is a difference of about 0.1 mg/dl in urinary creatinine measurements between a Jaffe and an enzymatic assay. 20 The advantage of our study is that we characterized the dynamics of Scr concentrations over the entire six weeks after birth in a quantitative manner rather than comparing the GFR values on separate days in ELBW cases. Second, controversy remains referring to the first creatinine concentration at birth. We observed lower Crea birth concentrations in the more extreme preterm neonates, which are born during the second trimester (median [95% CI]; 0.50 mg/dl [0.31 - 0.81] at 24 weeks GA, Table 4). ELBW neonates who are born in the third trimester (>28 weeks), were characterized by higher Crea birth Scr (median [95% CI]; 0.79 mg/dl [0.50-1.29] at 32 weeks GA). This trend is