Abstract

Transdermal analysis of glomerular filtration rate (GFR) is an established technique that is used to assess renal function in mouse and rat models of acute kidney injury and chronic kidney disease. The measurement system consists of a miniaturized fluorescence detector that is directly attached to the skin on the back of conscious, freely moving animals, and measures the excretion kinetics of the exogenous GFR tracer, fluorescein-isothiocyanate (FITC) conjugated sinistrin (an inulin analog). This system has been described in detail in rats. However, because of their smaller size, measurement of transcutaneous GFR in mice presents additional technical challenges. In this paper we therefore provide the first detailed practical guide to the use of transdermal GFR monitors in mice based on the combined experience of three different investigators who have been performing this assay in mice over a number of years.

Highlights

  • The use of transcutaneous glomerular filtration rate (GFR) monitors in mice was first reported by Schreiber and colleagues in 2012 and was validated by comparing GFR measurements obtained using this technique, with results obtained by direct measurement of FITC-sinistrin bolus clearance from serial blood samples[1]

  • Transdermal GFR measurements in rats and mice has been described in a number of publications[1,3,4,5], and a video tutorial demonstrating its use in rats has been published[6]

  • The transdermal monitor has been used in a variety of mouse strains and models of acute kidney injury (AKI) and CKD2

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Summary

Introduction

The use of transcutaneous GFR monitors in mice was first reported by Schreiber and colleagues in 2012 and was validated by comparing GFR measurements obtained using this technique, with results obtained by direct measurement of FITC-sinistrin bolus clearance from serial blood samples[1]. Transdermal measurement of FITC-sinistrin clearance has been shown to provide a more sensitive and accurate measure of renal function compared to the traditional parameters of renal function such as serum creatinine and blood urea nitrogen (BUN)[7,8]. The ability to measure GFR with high precision and sensitivity repeatedly in the same animal makes this technique attractive for a variety of different research disciplines. Experiments conducted at the University of Liverpool were performed under a license granted under the UK Animals (Scientific Procedures) Act 1986 and were approved by the University of Liverpool ethics committee.

Preparing the FITC-sinistrin
Mouse Preparation
Preparing the Transdermal GFR Monitor
Attaching the Transdermal GFR Monitor
FITC-sinistrin Injection
Measuring the GFR
Reading and Evaluating the Data
Representative Results
Discussion
Full Text
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