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.
Journal of the American Society of Nephrology : JASN. 2016 Feb 09 [Epub ahead of print]
Anupam Agarwal, Zheng Dong, Raymond Harris, Patrick Murray, Samir M Parikh, Mitchell H Rosner, John A Kellum, Claudio Ronco, Acute Dialysis Quality Initiative XIII Working Group
Division of Nephrology, and Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia;, Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, Tennessee;, Department of Medicine, University College of Dublin, Dublin, Ireland;, Division of Nephrology and Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts;, Department of Medicine, Nephrology Division, and the Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia;, Center for Critical Care Nephrology, Clinical Research, Investigation and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and. , Department of Nephrology, Dialysis, and Transplantation, San Bortolo Hospital, and the International Renal Research Institute, 36100 Vicenza, Italy.