NDT Advance Access published online on May 21, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp225
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Transcutaneous measurement of glomerular filtration rate using FITC-sinistrin in rats
1 InnovationLab GmbH, Speyerer Str. 4, D-69115 Heidelberg 2 Institute of Clinical Radiology and Nuclear Medicine 3 Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, D-68167 4 Department of Biotechnology, University of Applied Sciences, D-68163 5 HMKQ Quantitative Analytik, Tristanstr. 14, D-68199 6 Institute of Medical Statistics, Medical Faculty Mannheim, University of Heidelberg, D-68167 7 Roche Diagnostics GmbH, Sandhofer Str. 116, D-68305, Mannheim, Germany
Correspondence and offprint requests to: Daniel Schock-Kusch; E-mail: daniel.schock-kusch{at}innovationlab.biz
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Abstract |
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Background. Inulin/sinistrin (I/S) clearance is a gold standard for an accurate assessment of glomerular filtration rate (GFR). Here we describe and validate an approach for a transcutaneous determination of GFR by using fluorescein-isothiocyanate-labelled sinistrin (FITC-S) in rats.
Methods. Using a small animal imager, fluorescence is measured over the depilated ear of a rat after the injection of FITC-S. The decay curve of fluorescence is used for the calculation of half-life and GFR. The thus obtained transcutaneous data were validated by simultaneously performed enzymatic and fluorometric measurements in plasma of both FITC-S and sinistrin.
Results. The results of enzymatic sinistrin determination versus transcutaneous half-life of FITC-S or plasma fluorescence correlated well with each other (R2 > 0.90). Furthermore, Bland–Altman analyses proved a good degree of agreement of the three methods used. The measurements performed in healthy animals as well as different models of renal failure demonstrate its appropriateness in a wide range of renal function.
Conclusions. The transcutaneous method described offers a precise assessment of GFR in small animals. As neither blood and/or urine sampling nor time-consuming lab work is required, GFR can be determined immediately after the clearance procedure is finished. This method, therefore, simplifies and fastens GFR determinations in small lab animals compared to conventional bolus clearance techniques based on blood sampling. A low-cost device for the measurement of transcutaneous fluorescence intensity over time is under construction.
Keywords: FITC-S; GFR; transcutaneous measurement
* These authors contributed equally to this work.
Received for publication: 28. 1.09
Accepted in revised form: 24. 4.09