Bridging translation for acute kidney injury with better preclinical modeling of
human disease.
Authors Skrypnyk NI, Siskind LJ, Faubel S, de Caestecker MP
Submitted By Submitted Externally on 5/23/2018
Status Published
Journal American journal of physiology. Renal physiology
Year 2016
Date Published 5/1/2016
Volume : Pages 310 : F972 - 84
PubMed Reference 26962107
Abstract The current lack of effective therapeutics for patients with acute kidney injury
(AKI) represents an important and unmet medical need. Given the importance of
the clinical problem, it is time for us to take a few steps back and reexamine
current practices. The focus of this review is to explore the extent to which
failure of therapeutic translation from animal studies to human studies stems
from deficiencies in the preclinical models of AKI. We will evaluate whether the
preclinical models of AKI that are commonly used recapitulate the known
pathophysiologies of AKI that are being modeled in humans, focusing on four
common scenarios that are studied in clinical therapeutic intervention trials:
cardiac surgery-induced AKI; contrast-induced AKI; cisplatin-induced AKI; and
sepsis associated AKI. Based on our observations, we have identified a number of
common limitations in current preclinical modeling of AKI that could be
addressed. In the long term, we suggest that progress in developing better
preclinical models of AKI will depend on developing a better understanding of
human AKI. To this this end, we suggest that there is a need to develop greater
in-depth molecular analyses of kidney biopsy tissues coupled with improved
clinical and molecular classification of patients with AKI.

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