Transcutaneous measurement of glomerular filtration rate in small rodents: Through the skin for the win?

Abstract

This methods in renal research article describes a new non-invasive technique to measure glomerular filtration rate in small animals. Furthermore, this technology has potential for broader use in renal research, such as in measuring the rate of clearance of albumin from the circulation in animals with proteinuria. ABSTRACT:Rodent models of renal physiology and pathology are crucial to our understanding of the molecular, histological and functional sequelae that contribute to kidney diseases. One of the most important measures of renal function is glomerular filtration rate (GFR). While the accurate determination of GFR is pivotal to understanding the progression of disease and/or the benefits of treatment strategies, in rodents the conventional methods for assessment of GFR are inconvenient and cumbersome, not the least because they involve stress and often anaesthesia. The legitimacy of assay-based assessment of plasma and urine markers of GFR in mice has also been heavily scrutinized for their insensitivity to minor declines in GFR and inaccurate detection of renal biomarkers. While infusion-based clearance methods of GFR assessment are thus the gold standard in terms of accuracy, they are limited by the fact that they are primarily non-recovery procedures. This presents a dilemma when trying to document the progression of renal disease, as these measures cannot be taken in the same experimental subject. Here we review a technique of transcutaneous measurement of fluorescein isothiocyanate-labelled sinistrin to calculate GFR in small rodents, using a non-invasive clearance device (NIC-Kidney Device). This is a recently validated non-invasive technique for measuring GFR in small rodents that allows for the real-time measurement of GFR in conscious animals, without the need for plasma and urine assays.

Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy

“…a progressive decline in GFR. Previous studies have demonstrated the accuracy and reliability of the transcutaneous measurement of FITC-sinistrin half-life as a measure of GFR in various strains of rats and mice 10 11 18 20 21 22 23 . Of note, although remaining elevated, the degree of albuminuria fell between weeks 3 and 4.…”

Long-Term Endothelin-A Receptor Antagonism Provides Robust Renal Protection in Humanized Sickle Cell Disease Mice

“…GFR was measured in 14-week-old HbSS and HbAA mice (1 day before metabolic cage studies) using transcutaneous measurement of fluorescein isothiocyanate-labeled sinestrin technique as previously described. 64…”

Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy

“…On the day of GFR measurement, spiny mice were briefly (~5 min) anaesthetized (isoflurane), the photodiode recording device (NIC-Kidney Device) secured to the exposed skin with double-sided adhesive tape before giving an intracardiac injection of FITC-sinistrin (1.5 μl/g body weight of 35 mg/ml sinistrin in 0.9% NaCl; total volume 30-45 μl). Spiny mice were returned to their home cage and the elimination kinetics (halftime, t 1/2 ) recorded for the next 1 h (22).…”