A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia

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Krzyzanski W., Wintermark P., Annaert P., Groenendaal F., Şahin S., Öncel M. Y., ...Daha Fazla

AAPS Journal, cilt.26, sa.1, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1208/s12248-023-00851-0
  • Dergi Adı: AAPS Journal
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Anahtar Kelimeler: acute kidney injury, hypoxic-ischemic encephalopathy, neonates, population model, serum creatinine, therapeutic hypothermia, time-dependent covariate
  • Gazi Üniversitesi Adresli: Evet

Özet

The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR0). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased sCr in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the sCr synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher sCr synthesis rate compared to no-AKI patients. Our findings show that the use of sCr as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population. Graphical Abstract: [Figure not available: see fulltext.].