Experimental models of acute kidney injury for translational research

Neil A. Hukriede, Danielle E. Soranno, Veronika Sander, Tayla Perreau, Michelle C. Starr, Peter S.T. Yuen, Leah J. Siskind, Michael P. Hutchens, Alan J. Davidson, David M. Burmeister, Sarah Faubel, Mark P. de Caestecker*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations

Abstract

Preclinical models of human disease provide powerful tools for therapeutic discovery but have limitations. This problem is especially apparent in the field of acute kidney injury (AKI), in which clinical trial failures have been attributed to inaccurate modelling performed largely in rodents. Multidisciplinary efforts such as the Kidney Precision Medicine Project are now starting to identify molecular subtypes of human AKI. In addition, over the past decade, there have been developments in human pluripotent stem cell-derived kidney organoids as well as zebrafish, rodent and large animal models of AKI. These organoid and AKI models are being deployed at different stages of preclinical therapeutic development. However, the traditionally siloed, preclinical investigator-driven approaches that have been used to evaluate AKI therapeutics to date rarely account for the limitations of the model systems used and have given rise to false expectations of clinical efficacy in patients with different AKI pathophysiologies. To address this problem, there is a need to develop more flexible and integrated approaches, involving teams of investigators with expertise in a range of different model systems, working closely with clinical investigators, to develop robust preclinical evidence to support more focused interventions in patients with AKI.

Original languageEnglish
Pages (from-to)277-293
Number of pages17
JournalNature Reviews Nephrology
Volume18
Issue number5
DOIs
StatePublished - May 2022
Externally publishedYes

Fingerprint

Dive into the research topics of 'Experimental models of acute kidney injury for translational research'. Together they form a unique fingerprint.

Cite this