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Conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research : postnatal maturation of the glomerular filtration rate

Elke Gasthuys (UGent) , Joske Millecam (UGent) , Mathias Devreese (UGent) , Joris Delanghe (UGent) , Johan Vande Walle (UGent) , Marjolein Heyndrickx (UGent) and Siska Croubels (UGent)
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Abstract
Introduction: Adequate animal models are required to study the preclinical pharmacokinetics (PK), pharmacodynamics (PD) and safety of drugs in the pediatric subpopulation. Over the years, pigs were presented as a potential animal model, since they display a high degree of anatomical and physiological similarities with humans. Material and methods: The kidneys play a pivotal role in the PK and PD of various drugs, therefore, the glomerular filtration rate (GFR) measured as clearance of endogenous creatinine (Jaffe and enzymatic assay) and exo-iohexol was determined in conventional piglets aging 8 days (n =16), 4 weeks (n = 8) and 7 weeks (n = 16). The GFR data were normalized to bodyweight (BW), body surface area (BSA) and kidney weight (KW). Body Surface area is measured by X-ray Tomography. Results: GFR mesaured with iohexol and creatinine were comparible. Normalization to BW showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. Moreover, to facilitate the assessment of the GFR in growing piglets in subsequent studies, a formula was elaborated to estimate the GFR based on plasma creatinine and BW, namely eGFR =1.879× BW1.092. Conclusions: The postnatal development of the GFR was comparable with humans, rendering the piglet a convenient juvenile animal model for studying the PK, PD and safety of drugs in the pediatric subpopulation.

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Chicago
Gasthuys, Elke, Joske Millecam, Mathias Devreese, Joris Delanghe, Johan Vande Walle, Marjolein Heyndrickx, and Siska Croubels. 2018. “Conventional Growing Piglets as Potential Juvenile Animal Model for Preclinical Pharmaceutical Research : Postnatal Maturation of the Glomerular Filtration Rate.” In European Society for Paediatric Nephrology, 51st Annual Scientific Meeting, Abstracts.
APA
Gasthuys, E., Millecam, J., Devreese, M., Delanghe, J., Vande Walle, J., Heyndrickx, M., & Croubels, S. (2018). Conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research : postnatal maturation of the glomerular filtration rate. European Society for Paediatric Nephrology, 51st Annual scientific meeting, Abstracts. Presented at the 51st Annual scientific meeting of the European Society for Paediatric Nephrology (ESPN 2018).
Vancouver
1.
Gasthuys E, Millecam J, Devreese M, Delanghe J, Vande Walle J, Heyndrickx M, et al. Conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research : postnatal maturation of the glomerular filtration rate. European Society for Paediatric Nephrology, 51st Annual scientific meeting, Abstracts. 2018.
MLA
Gasthuys, Elke, Joske Millecam, Mathias Devreese, et al. “Conventional Growing Piglets as Potential Juvenile Animal Model for Preclinical Pharmaceutical Research : Postnatal Maturation of the Glomerular Filtration Rate.” European Society for Paediatric Nephrology, 51st Annual Scientific Meeting, Abstracts. 2018. Print.
@inproceedings{8576847,
  abstract     = {Introduction: Adequate animal models are required to study the preclinical pharmacokinetics (PK), pharmacodynamics (PD) and safety of drugs in the pediatric subpopulation. Over the years, pigs were presented as a potential animal model, since they display a high degree of anatomical and physiological similarities with humans.
Material and methods: The kidneys play a pivotal role in the PK and PD of various drugs, therefore, the glomerular filtration rate (GFR) measured as clearance of endogenous creatinine (Jaffe and enzymatic assay) and exo-iohexol was determined in conventional piglets aging 8 days (n =16), 4 weeks (n = 8) and 7 weeks (n = 16). The GFR data were normalized to bodyweight (BW), body surface area (BSA) and kidney weight (KW). Body Surface area is measured by X-ray Tomography.
Results: GFR mesaured with iohexol and creatinine were comparible. Normalization to BW showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. Moreover, to facilitate the assessment of the GFR in growing piglets in subsequent studies, a formula was elaborated to estimate the GFR based on plasma creatinine and BW, namely eGFR =1.879{\texttimes} BW1.092.
Conclusions: The postnatal development of the GFR was comparable with humans, rendering the piglet a convenient juvenile animal model for studying the PK, PD and safety of drugs in the pediatric subpopulation.},
  author       = {Gasthuys, Elke and Millecam, Joske and Devreese, Mathias and Delanghe, Joris and Vande Walle, Johan and Heyndrickx, Marjolein and Croubels, Siska},
  booktitle    = {European Society for Paediatric Nephrology, 51st Annual scientific meeting, Abstracts},
  language     = {eng},
  location     = {Antalya, Turkey},
  title        = {Conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research : postnatal maturation of the glomerular filtration rate},
  year         = {2018},
}