T MULLINS1,2, W SHENG TAN1, L GALLO1,2
1School Of Biomedical Sciences, The University of Queensland, St Lucia, Australia, 2Mater Research Institute-UQ, Translational Research Institute, Woollongabba, Australia
Aim: To validate a non-invasive transcutaneous method for assessing glomerular filtration rate (GFR) in obese mice.
Background: The measurement of GFR in experimental rodents is pivotal to understanding the progression of kidney disease and the benefits of treatment strategies. Traditional methods can be invasive, inaccurate, and/or labour-intensive. This has led to development of a non-invasive clearance device (NIC-Kidney), which measures transcutaneous decay of injected FITC-sinistrin in conscious rodents. The technique has been tested and used in a range of mouse models. However, simultaneous comparisons to an established method have not been performed, and the technique is yet to be validated in obese mice.
Methods: Five-week-old male C57BL/6J mice were randomised to either a high fat diet (60% kcal from fat, n=13) or normal diet (n=12) for 10 weeks. Body composition was measured using NMR mini-spec. Mice were subjected to a single retro-orbital injection of FITC-sinistrin (10mg/100g) and transcutaneous decay using the NIC-Kidney Device was simultaneously compared to plasma clearance (two-phase exponential decay) in the same, conscious mice.
Results: Mice randomised to high fat vs normal diet developed obesity (BW: 32.2 vs 26.6 g, fat mass: 23 vs 14%, P<0.01). In lean mice, there was a linear relationship between transcutaneous and plasma clearance GFR values (linear regression: P<0.05, R2 = 0.35), which remained when GFR was adjusted for body weight (linear regression: P<0.01, R2 = 0.48). This relationship between GFR values, using the two methods, was not evident in obese mice.
Conclusions: The non-invasive transcutaneous method for assessing GFR is suitable for use in lean, but not obese, mice. This may be due to impairments in cutaneous blood flow in obesity, which requires study.
Thomas Mullins completed a Bachelor of Science (First Class Honours) at The University of Queensland in 2017. His current research interests include diabetic nephropathy, anti-diabetic therapies that target the kidneys (SGLT2 inhibitors), and diabetes complications in pregnancy. Thomas is enrolled to commence a PhD project at The University of Queensland in the next academic quarter, supervised by Dr Helen Barrett, Dr Linda Gallo and Prof Karen Moritz. His PhD will focus on pregnancies complicated by type 2 diabetes mellitus, and associations of the microbiome with pregnancy and infant outcomes.