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Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
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Ontogeny of drug elimination by the human kidney

Nancy Chen1, Katarina Aleksa, Cindy Woodland

  • 1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.

Pediatric Nephrology (Berlin, Germany)
|December 7, 2005
PubMed

Insights

Toddlers exhibit an "overshoot" in glomerular filtration rate (GFR) and early adult levels of drug secretion. This necessitates higher renally excreted drug doses per kilogram in toddlers compared to adults.

Area of Science:

  • Pharmacology
  • Nephrology
  • Pediatric Drug Dosing

Background:

  • Renal clearance is a key pathway for drug elimination.
  • Neonatal renal function is immature, with rapid development post-birth.
  • Drug handling by the kidneys changes significantly throughout childhood.

Purpose of the Study:

  • To review the developmental changes in renal drug handling during childhood.
  • To explain the phenomenon of increased GFR and tubular secretion in toddlers.
  • To highlight the implications for drug dosing in young children.

Main Methods:

  • Literature review of studies on renal ontogeny and drug transport.
  • Analysis of pharmacokinetic data in pediatric populations.
  • Discussion of specific renal transport mechanisms in development.

Main Results:

  • Glomerular filtration rate (GFR) significantly exceeds adult levels in toddlers.
  • Active tubular secretion of drugs reaches adult levels early in childhood.
  • Toddlers demonstrate an "overshoot" in GFR due to developmental transport mechanisms.

Conclusions:

  • The unique renal physiology of toddlers leads to higher drug clearance.
  • Per-kilogram drug doses for renally eliminated medications must be adjusted for toddlers.
  • Understanding renal ontogeny is crucial for safe and effective pediatric pharmacotherapy.

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