BackgroundThe past years augmented renal clearance (ARC), observed in the critically ill paediatric population, has received an increased attention by researchers due to its major impact on drug exposure.1 Since a recent report demonstrated that the maturation of the glomerular filtration rate (GFR) in juvenile pigs is comparable to children, pigs may be a potential animal model to investigate the impact and mechanisms of ARC on drug pharmacokinetics (PK) in children.2In this pilot study, the contribution of intravenous (IV) fluid administration on the development of ARC was investigated in piglets.MethodsEight seven-week-old pigs underwent an experiment without fluid therapy and two consecutive fluid treatments as CRI of a 0.9% NaCl solution (3 mL/kg/h and 6 mL/kg/h) over 36 hours, each time combined with IV administration of a cocktail of renal markers after 4 and 24 h of fluid administration. This cocktail consisted of iohexol (64.7 mg/kg body weight (BW), Omnipaque 300®, marker for GFR) and para-aminohippuric acid (10 mg/kg BW, marker for effective renal plasma flow). To assess the impact of ARC on the PK of antimicrobials, amikacin (7,5 mg/kg BW, Amukin®) was administered after 24 h of fluid therapy. PK modelling was performed with Phoenix® WinNonlin®.ResultsGenerally, an increase in GFR was observed after fluid administration when compared to the GFR values observed without fluid administration. 4 and 2 out of 7 pigs demonstrated ARC after 4 h of a CRI at 3 mL/kg/h and 6 mL/kg/h, respectively. 4 out of 7 pigs displayed ARC after 24 h of a CRI at 3 mL/kg/h and 6 mL/kg/h. Similar results were obtained for amikacin clearance.ConclusionAn important effect of fluid therapy on the development of ARC was observed in juvenile pigs. Further research is necessary to confirm this results in critically ill children.ReferencesDhont E, et al. Augmented renal clearance in pediatric intensive care: are we undertreating our sickest patients? Pediatric Nephrology 2018.Gasthuys E, 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.Disclosure(s)This study was funded by the Special Research Fund of Ghent University (BOF16/DOC/285).
The kinetic glomerular filtration rate is not interchangeable with measured creatinine clearance for prediction of piperacillin underexposure in critically ill patients with augmented renal clearance
