Bridging translation for acute kidney injury with better preclinical modeling of human disease
Year: 2016
Type: review
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.
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Coordinating and Bioinformatics Unit for the MMPC/DiaComp, Small Molecule-Mediated Augmentation of Kidney Regeneration, Elucidating the cellular mechanisms of a pro-regenerative drug therapy for acute kidney injury, Pittsburgh Center for Kidney Research, Role of Ceramide-induced Kidney Cell Death in Acute Kidney Injury
OpenAlex ID: W2301240993