Does “Birth” as an Event Impact Maturation Trajectory of Renal Clearance via Glomerular Filtration? Reexamining Data in Preterm and Full‐Term Neonates by Avoiding the Creatinine Bias

Abstract

Glomerular filtration rate (GFR) is an important measure of renal function. Various models for its maturation have recently been compared; however, these have used markers, which are subject to different renal elimination processes. Inulin clearance data (a purer probe of GFR) collected from the literature were used to determine age-related changes in GFR aspects of renal drug excretion in pediatrics. An ontogeny model was derived using a best-fit model with various combinations of covariates such as postnatal age, gestational age at birth, and body weight. The model was applied to the prediction of systemic clearance of amikacin, gentamicin, vancomycin, and gadobutrol. During neonatal life, GFR increased as a function of both gestational age at birth and postnatal age, hence implying an impact of birth and a discrepancy in GFR for neonates with the same postmenstrual age depending on gestational age at birth (ie, neonates who were outside the womb longer had higher GFR, on average). The difference in GFR between pre-term and full-term neonates with the same postmenstrual age was negligible from beyond 1.25 years. Considering both postnatal age and gestational age at birth in GFR ontogeny models is important because postmenstrual age alone ignores the impact of birth. Most GFR models use covariates of body size in addition to age. Therefore, prediction from these models will also depend on the change in anthropometric characteristics with age. The latter may not be similar in various ethnic groups, and this makes the head-to-head comparison of models very challenging.

Glomerular Filtration Rate in Asphyxiated Neonates Under Therapeutic Whole-Body Hypothermia, Quantified by Mannitol Clearance

“…This is commonly accounted for in PK models using either PNA and/or PMA as covariates on CL [ 14 , 18 , 25 ]. However, several studies have suggested that PMA is insufficient to describe postnatal GFR maturation as it ignores the impact of birth on GFR [ 18 , 26 ]. Indeed, Salem et al showed that in a group of neonates with the same PMA values, neonates with a higher PNA have higher GFR values as compared with more mature cases at birth, but with a lower PNA [ 26 ].…”

“…However, several studies have suggested that PMA is insufficient to describe postnatal GFR maturation as it ignores the impact of birth on GFR [ 18 , 26 ]. Indeed, Salem et al showed that in a group of neonates with the same PMA values, neonates with a higher PNA have higher GFR values as compared with more mature cases at birth, but with a lower PNA [ 26 ]. In other words, postnatal GFR maturation is best described using PNA rather than PMA.…”

Comment on: "Preterm Physiologically Based Pharmacokinetic Model, Part I and Part II”

“…In those studies, the combination of gestational age or birthweight with postnatal age, and not PMA, were the best predictors of PK in a large heterogeneous group of preterm neonates. When it comes to renal function, the impact of birth on the maturation of glomerular filtration rate has recently been clearly shown by Salem et al [ 12 ].…”

Pediatric Drug‐Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations

“…The authors reported that the time to half the adult value of the glomerular filtration rate occurred at 47.7 weeks of post–menstrual age, suggesting that maturation in renal function will be an important predictor of clearance in neonates and infants 24 . Another study developed an ontogeny function based on postnatal age, gestational age at birth, and body weight and identified birth as an important determinant of glomerular filtration rate for pediatric patients fewer than 105 weeks post–menstrual age 25 . Another important consideration is that body size‐related developmental changes in organ size, composition, and perfusion occur disproportionately with age.…”