Improved kinetic model for the transcutaneous measurement of glomerular filtration rate in experimental animals.
Transcutaneous measurement of the glomerular filtration rate (tGFR) is now frequently used in animal studies.tGFR allows consecutive measurements on the same animal, including multiple measurements on a daily basis, because no blood sampling is required. Here we derive and validate a novel kinetic model for the description of transcutaneously measured FITC-Sinistrin excretion kinetics. In contrast to standard 1- to 3-compartment models, our model covers the complete kinetic, including injection and distribution of the tracer in the plasma compartment. Because the model describes the complete progression of the measurement, it allows further refinement by correcting for baseline shifts observed occasionally during measurement. Possible reasons for shifts in the background signal include photo bleaching of the skin, autofluorescence, changes of physiological state of the animals during the measurements, or effects arising from the attachment of the measurement device. Using the new 3-compartment kinetic model with modulated baseline (tGFR3cp.b.m),tGFR measurements in rats can reach comparable precision as those from GFR measurements assessed using a gold standard technique based on constant infusion of a tracer. Moreover, the variability of simultaneous (parallel) measurements, as well as repeatedtGFR measurements in the same animals, showed higher precision whentGFR3cp.b.mwas compared with the 1-compartmenttGFR1cpmodel.
Mannheim University of Applied Sciences, Institute for Process Control and Innovative Energy Conversion (PI) and Institute for Medical Technology of the University Heidelberg and the University of Applied Sciences Mannheim, Mannheim, Germany; Mannheim Pharma and Diagnostics GmbH, Mannheim, Germany. Electronic address: j.friedemann@mapdiagnostics.com.
Jochen
J
Friedemann
Freudenberg New Technologies SE, Weinheim, Germany.
Ralf
R
Heinrich
Mannheim University of Applied Sciences, Institute for Process Control and Innovative Energy Conversion (PI) and Institute for Medical Technology of the University Heidelberg and the University of Applied Sciences Mannheim, Mannheim, Germany; Mannheim Pharma and Diagnostics GmbH, Mannheim, Germany.
Yury
Y
Shulhevich
Mannheim University of Applied Sciences, Institute for Process Control and Innovative Energy Conversion (PI) and Institute for Medical Technology of the University Heidelberg and the University of Applied Sciences Mannheim, Mannheim, Germany.
Matthias
M
Raedle
AstraZeneca R&D, Bioscience CKD Gothenburg, Sweden.
Lena
L
William-Olsson
Mannheim Pharma and Diagnostics GmbH, Mannheim, Germany.
Johannes
J
Pill
Mannheim University of Applied Sciences, Institute for Process Control and Innovative Energy Conversion (PI) and Institute for Medical Technology of the University Heidelberg and the University of Applied Sciences Mannheim, Mannheim, Germany; Mannheim Pharma and Diagnostics GmbH, Mannheim, Germany.
Daniel
D
Schock-Kusch
D000818:Animals; D001699:Biometry; D005919:Glomerular Filtration Rate; D007700:Kinetics; D008297:Male; D023421:Models, Animal; D008962:Models, Theoretical; D017207:Rats, Sprague-Dawley
FITC-sinistrin; glomerular filtration rate; transcutaneous