title: Bridging Translation by Improving Preclinical Study Design in AKI.
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.
authors.affiliation: Division of Nephology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee; mark.de.caestecker@vanderbilt.edu sarah.faubel@ucdenver.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: de Caestecker
authors.affiliation: Division of Renal Diseases, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Ben D
authors.initials: BD
authors.lastname: Humphreys
authors.affiliation: Division of Nephrology, Department of Medicine, University of California, San Francisco, California;
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.affiliation: Division of Nephology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
authors.affiliation: Division of Nephrology and Hypertension, Albany Medical College, Albany, New York;
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerda
authors.affiliation: Renal-Electrolyte Division, Department of Medicine and Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Nolin
authors.affiliation: Department of Pediatrics, Division of Nephrology, University of Alabama, Birmingham, Alabama;
authors.forename: David
authors.initials: D
authors.lastname: Askenazi
authors.affiliation: Renal-Electrolyte Division, Department of Medicine and Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors.forename: Girish
authors.initials: G
authors.lastname: Mour
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Frank E
authors.initials: FE
authors.lastname: Harrell
authors.affiliation: Pfizer Global Research and Development, Inflammation & Immunology Research Unit, Cambridge, Massachusetts;
authors.forename: Nick
authors.initials: N
authors.lastname: Pullen
authors.affiliation: Division of Nephrology, Department of Medicine, University of California, San Francisco, California; Division of Nephrology, Department of Medicine, University of California, San Francisco, California;
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.affiliation: Renal Division, University of Colorado Denver and Denver Veterans Affairs Medical Center, Aurora, Colorado mark.de.caestecker@vanderbilt.edu sarah.faubel@ucdenver.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D012107:Research Design / Q000592:standards*; D017693:Sodium Bicarbonate / Q000627:therapeutic use; D057170:Translational Research, Biomedical / Q000592:standards*
chemical_list: D003287:Contrast Media; D016166:Free Radical Scavengers; D004921:Erythropoietin; D017693:Sodium Bicarbonate; D000111:Acetylcysteine
keywords: acute kidney injury; preclinical research; reproducibility