Progress in the development of animal models of acute kidney injury and its impact on drug discovery

Abstract

Introduction: Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches.

Areas covered: The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery.

Expert opinion: New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Keywords::

• apoptosis
• fibrosis
• inflammation
• kidney
• necroptosis
• nephrotoxicity
• transgenic mice
• TWEAK

Acknowledgements

The authors have received support from the Instituto de Salud Carlos III through the grants FIS PS09/00447, ISCIII-RETIC, REDinREN/RD06/0016. Furthermore, they have received support via the European Regional Development Fund (FEDER), RD12/0021 and the Comunidad de Madrid/CIFRA S2010/BMD-2378. The authors have also received support via the Instituto de Salud Carlos III in the form of: MD Sanchez-Niño has received a FIS-Sara Borrell post-doctoral fellowship; AM Ramos and A Sanz have received a post-doctoral Miguel Servet fellowship, while A Ortiz has received salary support through the Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM). Finally C Martin-Cleary is the recipient of a ‘Rio Hortega' fellowship grant from the Instituto de Salud Carlos III.

Notes

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