Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy.
Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers.
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Lauren
L
Scarfe
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Aleksandra
A
Rak-Raszewska
Medical Research Centre, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Stefania
S
Geraci
Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Darsy
D
Darssan
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Jack
J
Sharkey
Medical Research Centre, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Jiaguo
J
Huang
iThera Medical, Munich, Germany.
Neal C
NC
Burton
Centre for Cell Imaging, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
David
D
Mason
Centre for Paediatrics and Child Health, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Parisa
P
Ranjzad
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Simon
S
Kenny
Medical Research Centre, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Norbert
N
Gretz
Centre for Cell Imaging, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
Raphaël
R
Lévy
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
B
B
Kevin Park
Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Marta
M
García-Fiñana
Centre for Paediatrics and Child Health, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Adrian S
AS
Woolf
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Patricia
P
Murray
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Bettina
B
Wilm
D000419:Albuminuria / Q000150:complications; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D006207:Half-Life; D007211:Indoles / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology*; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000473:pathology* / Q000503:physiopathology*; D007700:Kinetics; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015233:Models, Statistical; D009398:Nephrology / Q000379:methods*; D009844:Oligosaccharides / Q000378:metabolism; D061088:Photoacoustic Techniques
D015415:Biomarkers; D005452:Fluoresceins; D007211:Indoles; D009844:Oligosaccharides; C576250:fluorescein-isothiocyanate sinistrin; D004317:Doxorubicin