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Updated: Mar 30, 2026
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Bridging Translation by Improving Preclinical Study Design in AKI
Mark de Caestecker1, Ben D Humphreys2, Kathleen D Liu3
1Division of Nephology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee; 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.
Insights
Improving preclinical study design is crucial for advancing acute kidney injury (AKI) research. This review identifies weaknesses in current study designs to enhance the translation of basic AKI research into clinical practice.
Area of Science:
- Nephrology
- Translational Medicine
- Drug Development
Background:
- No effective therapeutic interventions currently exist to prevent, treat, or slow the progression of acute kidney injury (AKI) to chronic kidney disease (CKD).
- The poor translation of preclinical AKI research findings into clinical practice is a significant challenge, with animal models often failing to predict human therapeutic responses.
- While the utility of animal models is debated, improving preclinical study design may enhance the translatability of AKI research using existing models.
Purpose of the Study:
- To identify common weaknesses in study design and reporting within preclinical AKI research.
- To provide evidence-based recommendations for improving the quality and translatability of AKI research.
- To inform the development of guidelines for preclinical AKI drug development.
Main Methods:
- An evidence-based review approach was employed to analyze common flaws in preclinical AKI study design and reporting.
- Focused analysis on extensively studied therapeutic approaches, including N-acetylcysteine and sodium bicarbonate for contrast-induced AKI, and erythropoietin for AKI prevention.
- Examined findings from clinical trials related to these therapeutic interventions.
Main Results:
- Identified specific, common weaknesses in the design and reporting of preclinical AKI studies.
- Highlighted five key areas requiring improvement in preclinical study design and reporting practices.
- Found that existing therapeutic approaches like N-acetylcysteine, sodium bicarbonate, and erythropoietin have been extensively studied but translation remains a challenge.
Conclusions:
- Improvements in preclinical study design and reporting are essential to enhance the translatability of AKI research.
- The identified areas for improvement offer preliminary guidelines to strengthen preclinical research for AKI drug development.
- Addressing these weaknesses may increase the likelihood of successful translation from basic research to clinical applications for AKI treatment.
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