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Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research

Elke Gasthuys (UGent) , Mathias Devreese (UGent) , Joske Millecam (UGent) , Stanislas Sys (UGent) , Katrien Vanderperren (UGent) , Joris Delanghe (UGent) , Johan Vande Walle (UGent) , Marjolein Heyndrickx (UGent) and Siska Croubels (UGent)
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Abstract
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. To assess the suitability of piglets as a preclinical animal model for children, the ontogeny and maturation processes of several organ systems have to be unraveled and compared between both species. 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). Normalization to BSA and KW showed an increase in GFR from 46.57 to 100.92 mL/min/m2 and 0.49 to 1.51 mL/min/g KW from 8 days to 7 weeks of age, respectively. Normalization to BW showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. 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. 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 × BW^1.092/Pcr^0.600.
Keywords
piglet, glomerular filtration rate, iohexol, creatinine, pediatric animal model, RENAL-FUNCTION, ENDOGENOUS CREATININE, SERUM CREATININE, CLEARANCE, CHILDREN, PREDICTION, CR-51-EDTA, EQUATIONS, IOHEXOL, GROWTH

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Chicago
Gasthuys, Elke, Mathias Devreese, Joske Millecam, Stanislas Sys, Katrien Vanderperren, Joris Delanghe, Johan Vande Walle, Marjolein Heyndrickx, and Siska Croubels. 2017. “Postnatal Maturation of the Glomerular Filtration Rate in Conventional Growing Piglets as Potential Juvenile Animal Model for Preclinical Pharmaceutical Research.” Frontiers in Pharmacology 8.
APA
Gasthuys, E., Devreese, M., Millecam, J., Sys, S., Vanderperren, K., Delanghe, J., Vande Walle, J., et al. (2017). Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research. FRONTIERS IN PHARMACOLOGY, 8.
Vancouver
1.
Gasthuys E, Devreese M, Millecam J, Sys S, Vanderperren K, Delanghe J, et al. Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research. FRONTIERS IN PHARMACOLOGY. 2017;8.
MLA
Gasthuys, Elke, Mathias Devreese, Joske Millecam, et al. “Postnatal Maturation of the Glomerular Filtration Rate in Conventional Growing Piglets as Potential Juvenile Animal Model for Preclinical Pharmaceutical Research.” FRONTIERS IN PHARMACOLOGY 8 (2017): n. pag. Print.
@article{8526001,
  abstract     = {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. To assess the suitability of piglets as a preclinical animal model for children, the ontogeny and maturation processes of several organ systems have to be unraveled and compared between both species. 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). Normalization to BSA and KW showed an increase in GFR from 46.57 to 100.92 mL/min/m2 and 0.49 to 1.51 mL/min/g KW from 8 days to 7 weeks of age, respectively. Normalization to BW showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. 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. 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} BW\^{ }1.092/Pcr\^{ }0.600.},
  articleno    = {431},
  author       = {Gasthuys, Elke and Devreese, Mathias and Millecam, Joske and Sys, Stanislas and Vanderperren, Katrien and Delanghe, Joris and Vande Walle, Johan and Heyndrickx, Marjolein and Croubels, Siska},
  issn         = {1663-9812},
  journal      = {FRONTIERS IN PHARMACOLOGY},
  keyword      = {piglet,glomerular filtration rate,iohexol,creatinine,pediatric animal model,RENAL-FUNCTION,ENDOGENOUS CREATININE,SERUM CREATININE,CLEARANCE,CHILDREN,PREDICTION,CR-51-EDTA,EQUATIONS,IOHEXOL,GROWTH},
  language     = {eng},
  pages        = {7},
  title        = {Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research},
  url          = {http://dx.doi.org/10.3389/fphar.2017.00431},
  volume       = {8},
  year         = {2017},
}

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