title: Rapid diagnosis and quantification of acute kidney injury using fluorescent ratio-metric determination of glomerular filtration rate in the rat.
abstract: The rapid diagnosis and quantification of acute kidney injury (AKI) severity remain high clinical priorities. By combining intravital fluorescent ratiometric two-photon kidney imaging and the two-compartment pharmacokinetics model, we demonstrate that rapid quantification of glomerular filtration rate (GFR) can be achieved in physiologic and AKI rat kidney models. Using a bolus infusion of a mixture of FITC-inulin and a 500-kDa Texas Red dextran, a full spectrum of GFR values, ranging from 0.17 to 1.12 ml·min(-1)·100 g(-1), was obtained. The GFR values thus determined correlated well with values obtained by the standard 2-h inulin infusion clearance method with a Pearson's correlation coefficient of 0.85. In addition, postischemia deterioration was studied by measuring GFR using the two-photon approach during 24 h following a 45-min bilateral ischemia clamp model. The GFR was found to decline sharply during the initial 4 h followed by a nadir with little sign of rising over the ensuing 24-h period. Moreover, a FITC-labeled 5-kDa dextran was identified as having nearly identical filtration characteristics as FITC-inulin, but had markedly increased fluorescent intensity, thus minimizing the quantity needed for individual studies. The technique reported allows for very rapid GFR determinations, within 10-15 min, based on plasma clearance of a freely filtered fluorescence probe, instead of a prolonged one-compartment interstitial space reporter molecule clearance employed by other technologies.
authors.affiliation: Nephrology Div., Dept. of Medicine, Indiana Univ. School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Exing
authors.initials: E
authors.lastname: Wang
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Campos
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D000465:Algorithms; D000818:Animals; D003627:Data Interpretation, Statistical; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005839:Gentamicins; D005919:Glomerular Filtration Rate / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007444:Inulin / Q000378:metabolism; D007511:Ischemia / Q000473:pathology; D007677:Kidney Function Tests / Q000379:methods*; D008070:Lipopolysaccharides; D008297:Male; D018613:Microscopy, Confocal; D011500:Protein Synthesis Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005839:Gentamicins; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D007444:Inulin; D016650:Fluorescein-5-isothiocyanate