Bridging translation by improving preclinical study design in AKI

Mark De Caestecker, Ben D. Humphreys, Kathleen D. Liu, William H. Fissell, Jorge Cerda, Thomas D. Nolin, David Askenazi, Girish Mour, Frank E. Harrell, Nick Pullen, Mark D. Okusa, Sarah Faubel

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

Abstract

Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings.We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrastinduced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.

Original languageEnglish
Pages (from-to)2905-2916
Number of pages12
JournalJournal of the American Society of Nephrology
Volume26
Issue number12
DOIs
StatePublished - Dec 2015

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