TY - JOUR
T1 - Experimental models of acute kidney injury for translational research
AU - Hukriede, Neil A.
AU - Soranno, Danielle E.
AU - Sander, Veronika
AU - Perreau, Tayla
AU - Starr, Michelle C.
AU - Yuen, Peter S.T.
AU - Siskind, Leah J.
AU - Hutchens, Michael P.
AU - Davidson, Alan J.
AU - Burmeister, David M.
AU - Faubel, Sarah
AU - de Caestecker, Mark P.
N1 - Publisher Copyright:
© 2022, Springer Nature Limited.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124826774&partnerID=8YFLogxK
U2 - 10.1038/s41581-022-00539-2
DO - 10.1038/s41581-022-00539-2
M3 - Review article
C2 - 35173348
AN - SCOPUS:85124826774
SN - 1759-5061
VL - 18
SP - 277
EP - 293
JO - Nature Reviews Nephrology
JF - Nature Reviews Nephrology
IS - 5
ER -