Cellular and Molecular Mechanisms of AKI
Author(s) -
Anupam Agarwal,
Zheng Dong,
Raymond C. Harris,
Patrick Murray,
Samir M. Parikh,
Mitchell H. Rosner,
John A. Kellum,
Claudio Ronco
Publication year - 2016
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2015070740
Subject(s) - context (archaeology) , medicine , clinical trial , intensive care medicine , diabetes mellitus , bioinformatics , clinical significance , harmonization , relevance (law) , psychological intervention , pathology , biology , paleontology , physics , political science , acoustics , law , endocrinology , psychiatry
In this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed. Comorbidities that could alter patient susceptibility to AKI, such as underlying diabetes, aging, obesity, cancer, and CKD, should also be considered in developing these models. Finally, harmonization between academia and industry for more clinically relevant preclinical testing of potential therapeutic targets and better translational clinical trial design is also needed to achieve the goal of developing effective interventions for AKI.
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