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

Abstract

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.

Constrained Inversion and Spectral Unmixing in Multispectral Optoacoustic Tomography

“…MSOT images at 715, 730, 760, 780, 800 and 850 nm wavelengths were subsequently taken without averaging approximately 4 min post injection at the kidney region, where the probe accumulates during renal clearance [46]. …”

Advanced optoacoustic methods for multiscale imaging of in vivo dynamics

“…Gray-scale background represents single-wavelength optoacoustic reconstructions whereas the spectrally-unmixed dye distribution is superimposed in color. Figure is used under the Creative Commons Attribution 4.0 International License from [94]. A scale bar was added and image identification was altered.…”

Light‐Emitting Agents for Noninvasive Assessment of Kidney Function

“…For example, the PPB of the commercial anionic dye IRDye800CW (Figure a) is as high as 41 %. Although kidney clearance of IRDye800CW can be determined by multispectral optoacoustic tomography (MSOT), its plasma clearance curves have no decay at 90 min postinjection upon using transcutaneous measurements . These studies further confirm that rapid accumulation and long retention of conventional organic fluorophores in the skin is a dilemma for the noninvasive transcutaneous measurement of renal function.…”