Overcoming translational barriers in acute kidney injury: A report from an NIDDK workshop

Anna Zuk, Paul M. Palevsky, Linda Fried, Frank E. Harrell, Samina Khan, Dianne B. McKay, Luke Devey, Lakhmir Chawla, Mark de Caestecker, James S. Kaufman, B. Taylor Thompson, Anupam Agarwal, Tom Greene, Mark Douglas Okusa, Joseph V. Bonventre, Laura M. Dember, Kathleen D. Liu, Benjamin D. Humphreys, Daniel Gossett, Yining XieJenna M. Norton, Paul L. Kimmel, Robert A. Star

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

AKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “AKI Outcomes: Overcoming Barriers in AKI” workshop on February 10–12, 2015. The workshop used a reverse translational medicine approach to identify steps necessary to achieve clinical success. During the workshop, breakout groups werecharged firstto design feasible, phase 2, proof-of-concept clinical trials for delayed transplant graft function, prevention of AKI (primary prevention), and treatment of AKI (secondary prevention and recovery). Breakout groups then were responsible for identification of preclinical animal models that would replicate the pathophysiology of the phase 2 proof-of-concept patient population, including primary and secondary end points. Breakout groups identified considerable gaps in knowledge regarding human AKI, our understanding of the pathophysiology of AKI in preclinical animal models, and the fidelity of cellular and molecular targets that have been evaluated preclinically to provide information regarding human AKI of various etiologies. The workshop concluded with attendees defining a new path forward to a better understanding of the etiology, pathology, and pathophysiology of human AKI.

Original languageEnglish
Pages (from-to)1113-1123
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Volume13
Issue number7
DOIs
StatePublished - Jul 6 2018

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