title: Online feedback-controlled renal constant infusion clearances in rats.
abstract: Constant infusion clearance techniques using exogenous renal markers are considered the gold standard for assessing the glomerular filtration rate. Here we describe a constant infusion clearance method in rats allowing the real-time monitoring of steady-state conditions using an automated closed-loop approach based on the transcutaneous measurement of the renal marker FITC-sinistrin. In order to optimize parameters to reach steady-state conditions as fast as possible, a Matlab-based simulation tool was established. Based on this, a real-time feedback-regulated approach for constant infusion clearance monitoring was developed. This was validated by determining hourly FITC-sinistrin plasma concentrations and the glomerular filtration rate in healthy and unilaterally nephrectomized rats. The transcutaneously assessed FITC-sinistrin fluorescence signal was found to reflect the plasma concentration. Our method allows the precise determination of the onset of steady-state marker concentration. Moreover, the steady state can be monitored and controlled in real time for several hours. This procedure is simple to perform since no urine samples and only one blood sample are required. Thus, we developed a real-time feedback-based system for optimal regulation and monitoring of a constant infusion clearance technique.
authors.affiliation: Medical Research Centre, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schock-Kusch
authors.forename: Yury
authors.initials: Y
authors.lastname: Shulhevich
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Juergen
authors.initials: J
authors.lastname: Hesser
authors.forename: Dzmitry
authors.initials: D
authors.lastname: Stsepankou
authors.forename: Sabine
authors.initials: S
authors.lastname: Neudecker
authors.forename: Jochen
authors.initials: J
authors.lastname: Friedemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Koenig
authors.forename: Ralf
authors.initials: R
authors.lastname: Heinrich
authors.forename: Friederike
authors.initials: F
authors.lastname: Hoecklin
authors.forename: Johannes
authors.initials: J
authors.lastname: Pill
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
mesh_terms: D000818:Animals; D003198:Computer Simulation; D025461:Feedback, Physiological; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D007263:Infusions, Parenteral; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests / Q000379:methods*; D008297:Male; D008954:Models, Biological; D009392:Nephrectomy; D009844:Oligosaccharides / Q000008:administration & dosage / Q000097:blood; D009862:Online Systems; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009844:Oligosaccharides; D016650:Fluorescein-5-isothiocyanate; C064636:sinistrin