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J Am Soc Nephrol. 2015 Dec;26(12):2905-16. doi: 10.1681/ASN.2015070832. Epub 2015 Nov 4.

Bridging Translation by Improving Preclinical Study Design in AKI.

Author information

1
Division of Nephology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee; mark.de.caestecker@vanderbilt.edu sarah.faubel@ucdenver.edu.
2
Division of Renal Diseases, Washington University School of Medicine, St. Louis, Missouri;
3
Division of Nephrology, Department of Medicine, University of California, San Francisco, California;
4
Division of Nephology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee;
5
Division of Nephrology and Hypertension, Albany Medical College, Albany, New York;
6
Renal-Electrolyte Division, Department of Medicine and Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
7
Department of Pediatrics, Division of Nephrology, University of Alabama, Birmingham, Alabama;
8
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee;
9
Pfizer Global Research and Development, Inflammation & Immunology Research Unit, Cambridge, Massachusetts;
10
Division of Nephrology, Department of Medicine, University of California, San Francisco, California; Division of Nephrology, Department of Medicine, University of California, San Francisco, California;
11
Renal Division, University of Colorado Denver and Denver Veterans Affairs Medical Center, Aurora, Colorado mark.de.caestecker@vanderbilt.edu sarah.faubel@ucdenver.edu.

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 contrast-induced 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.

KEYWORDS:

acute kidney injury; preclinical research; reproducibility

PMID:
26538634
PMCID:
PMC4657852
DOI:
10.1681/ASN.2015070832
[Indexed for MEDLINE]
Free PMC Article

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