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Review
. 2020 May 19;21(10):3587.
doi: 10.3390/ijms21103587.

Revisiting Experimental Models of Diabetic Nephropathy

Anna Giralt-López  1 , Mireia Molina-Van den Bosch  1 , Ander Vergara  1   2 , Clara García-Carro  1   2 , Daniel Seron  1   2 , Conxita Jacobs-Cachá  1 , Maria José Soler  1   2
Affiliations
Review

Revisiting Experimental Models of Diabetic Nephropathy

Anna Giralt-López et al. Int J Mol Sci. .

Abstract

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.

Keywords: diabetic nephropathy; experimental models of DN; histological lesions; renal function.

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Conflict of interest statement

C.G.C reports honorarium for conferences and advisory boards from Astra Zeneca and Boehringer Ingelheim and travel support from Astellas, Menarini, Novartis, Esteve, Sanofi and Novonordisk. M.J.S. has received speaker fees or travel support from Otsuka, Menarini, Astrazeneca, Boehringer Ingelheim, Janssen, Mundipharma, Novartis, Eli Lilly, Esteve and Novonordisk.

Figures

Figure 1
Figure 1
Transcutaneous glomerular filtration rate measurement technique. (A) Transcutaneous measuring device and its components. (B), The device is placed in the shaved back of the mouse anesthetized with isoflurane. Adhesive tape is also used to properly fix the device and avoid movement artefacts. (C), Once attached and after fluorescein isothiocyanate (FITC)-sinistrin administration, the mouse can move freely during measuring period.
Figure 2
Figure 2
Transcutaneous measuring results fitted to a decay curve. (A), Wrong transcutaneous glomerular filtration rate (GFR) measurement. After skin background measurement there is no signal peak, as FITC-sinistrin was not correctly administered intravenously. (B) Correct transcutaneous GFR measurement. The curve shows a basal measurement of the skin background followed by a signal peak after FITC-sinistrin intravenous bolus administration.
See this image and copyright information in PMC

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