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

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 lit...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2021-02, Vol.61 (2), p.159-171
Main Authors: Salem, Farzaneh, Johnson, Trevor N., Hodgkinson, Arran B. J., Ogungbenro, Kayode, Rostami‐Hodjegan, Amin
Format: Article
Language:English
Subjects:
Age
Amikacin
Birth
Body size
Body weight
Creatinine
Gentamicin
Gestational age
Glomerular filtration rate
Inulin
maturation
Minority & ethnic groups
Neonates
Newborn babies
Ontogeny
Pediatric Pharmacology
Renal function
Uterus
Vancomycin
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Summary: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.
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.1725