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The development of a juvenile porcine augmented renal clearance model through continuous infusion of lipopolysaccharides : an exploratory study

Laura Dhondt (UGent) , Siska Croubels (UGent) , Robin Temmerman (UGent) , Pieter De Cock (UGent) , Evelyne Meyer (UGent) , Wim Van Den Broeck (UGent) , Peter De Paepe (UGent) and Mathias Devreese (UGent)
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Abstract
Augmented renal clearance (ARC) as observed in the critically ill (pediatric) population can have a major impact on the pharmacokinetics and posology of renally excreted drugs. Although sepsis has been described as a major trigger in the development of ARC in human critically ill patients, mechanistic insights on ARC are currently lacking. An appropriate ARC animal model could contribute to reveal these underlying mechanisms. In this exploratory study, a state of ARC was induced in 8-week-old piglets. Conscious piglets were continuously infused over 36 h with lipopolysaccharides (LPS) from Escherichia coli (O111:B4) to induce sepsis and subsequently trigger ARC. To study the dose-dependent effect of LPS on the renal function, three different doses (0.75, 2.0, 5.0 mu g/kg/h) were administered (two male piglets/dose, one sham piglet), in combination with fluid administration (0.9% NaCl) at 6 ml/kg/h. Single boluses of renal markers, i.e., creatinine [40 mg/kg body weight (BW)], iohexol (64.7 mg/kg BW), and para-aminohippuric acid (PAH, 10 mg/kg BW) were administered intravenously to evaluate the effect of LPS on the renal function. Clinical parameters were monitored periodically. Blood sampling was performed to determine the effect on hematology, neutrophil gelatinase-associated lipocalin, and prostaglandin E-2 plasma levels. All piglets that were continuously infused with LPS displayed an elevated body temperature, heart rhythm, and respiratory rate similar to 1-3 h after start of the infusion. After infusion, considerably higher total body clearances of iohexol, creatinine, and PAH were observed, independent of the administration of LPS and/or its dose. Since also the sham piglet, receiving no LPS, demonstrated a comparable increase in renal function, the contribution of fluid administration to the development of ARC should be further evaluated.
Keywords
GELATINASE-ASSOCIATED LIPOCALIN, ACUTE KIDNEY INJURY, CREATININE CLEARANCE, EXOGENOUS CREATININE, NEPHROPATHY SYNDROME, IMMUNE-RESPONSES, ANIMAL-MODELS, INDUCED FEVER, BLOOD-FLOW, SEPSIS, piglet, lipopolysaccharides, sepsis animal model, augmented renal clearance, continuous infusion

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MLA
Dhondt, Laura, et al. “The Development of a Juvenile Porcine Augmented Renal Clearance Model through Continuous Infusion of Lipopolysaccharides : An Exploratory Study.” FRONTIERS IN VETERINARY SCIENCE, vol. 8, 2021, doi:10.3389/fvets.2021.639771.
APA
Dhondt, L., Croubels, S., Temmerman, R., De Cock, P., Meyer, E., Van Den Broeck, W., … Devreese, M. (2021). The development of a juvenile porcine augmented renal clearance model through continuous infusion of lipopolysaccharides : an exploratory study. FRONTIERS IN VETERINARY SCIENCE, 8. https://doi.org/10.3389/fvets.2021.639771
Chicago author-date
Dhondt, Laura, Siska Croubels, Robin Temmerman, Pieter De Cock, Evelyne Meyer, Wim Van Den Broeck, Peter De Paepe, and Mathias Devreese. 2021. “The Development of a Juvenile Porcine Augmented Renal Clearance Model through Continuous Infusion of Lipopolysaccharides : An Exploratory Study.” FRONTIERS IN VETERINARY SCIENCE 8. https://doi.org/10.3389/fvets.2021.639771.
Chicago author-date (all authors)
Dhondt, Laura, Siska Croubels, Robin Temmerman, Pieter De Cock, Evelyne Meyer, Wim Van Den Broeck, Peter De Paepe, and Mathias Devreese. 2021. “The Development of a Juvenile Porcine Augmented Renal Clearance Model through Continuous Infusion of Lipopolysaccharides : An Exploratory Study.” FRONTIERS IN VETERINARY SCIENCE 8. doi:10.3389/fvets.2021.639771.
Vancouver
1.
Dhondt L, Croubels S, Temmerman R, De Cock P, Meyer E, Van Den Broeck W, et al. The development of a juvenile porcine augmented renal clearance model through continuous infusion of lipopolysaccharides : an exploratory study. FRONTIERS IN VETERINARY SCIENCE. 2021;8.
IEEE
[1]
L. Dhondt et al., “The development of a juvenile porcine augmented renal clearance model through continuous infusion of lipopolysaccharides : an exploratory study,” FRONTIERS IN VETERINARY SCIENCE, vol. 8, 2021.
@article{8706526,
  abstract     = {{Augmented renal clearance (ARC) as observed in the critically ill (pediatric) population can have a major impact on the pharmacokinetics and posology of renally excreted drugs. Although sepsis has been described as a major trigger in the development of ARC in human critically ill patients, mechanistic insights on ARC are currently lacking. An appropriate ARC animal model could contribute to reveal these underlying mechanisms. In this exploratory study, a state of ARC was induced in 8-week-old piglets. Conscious piglets were continuously infused over 36 h with lipopolysaccharides (LPS) from Escherichia coli (O111:B4) to induce sepsis and subsequently trigger ARC. To study the dose-dependent effect of LPS on the renal function, three different doses (0.75, 2.0, 5.0 mu g/kg/h) were administered (two male piglets/dose, one sham piglet), in combination with fluid administration (0.9% NaCl) at 6 ml/kg/h. Single boluses of renal markers, i.e., creatinine [40 mg/kg body weight (BW)], iohexol (64.7 mg/kg BW), and para-aminohippuric acid (PAH, 10 mg/kg BW) were administered intravenously to evaluate the effect of LPS on the renal function. Clinical parameters were monitored periodically. Blood sampling was performed to determine the effect on hematology, neutrophil gelatinase-associated lipocalin, and prostaglandin E-2 plasma levels. All piglets that were continuously infused with LPS displayed an elevated body temperature, heart rhythm, and respiratory rate similar to 1-3 h after start of the infusion. After infusion, considerably higher total body clearances of iohexol, creatinine, and PAH were observed, independent of the administration of LPS and/or its dose. Since also the sham piglet, receiving no LPS, demonstrated a comparable increase in renal function, the contribution of fluid administration to the development of ARC should be further evaluated.}},
  articleno    = {{639771}},
  author       = {{Dhondt, Laura and Croubels, Siska and Temmerman, Robin and De Cock, Pieter and Meyer, Evelyne and Van Den Broeck, Wim and De Paepe, Peter and Devreese, Mathias}},
  issn         = {{2297-1769}},
  journal      = {{FRONTIERS IN VETERINARY SCIENCE}},
  keywords     = {{GELATINASE-ASSOCIATED LIPOCALIN,ACUTE KIDNEY INJURY,CREATININE CLEARANCE,EXOGENOUS CREATININE,NEPHROPATHY SYNDROME,IMMUNE-RESPONSES,ANIMAL-MODELS,INDUCED FEVER,BLOOD-FLOW,SEPSIS,piglet,lipopolysaccharides,sepsis animal model,augmented renal clearance,continuous infusion}},
  language     = {{eng}},
  pages        = {{13}},
  title        = {{The development of a juvenile porcine augmented renal clearance model through continuous infusion of lipopolysaccharides : an exploratory study}},
  url          = {{http://dx.doi.org/10.3389/fvets.2021.639771}},
  volume       = {{8}},
  year         = {{2021}},
}

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