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A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
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Acute kidney injury urinary biomarker time-courses
John W Pickering1, Zoltán H Endre2
1Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
Plos One
|July 10, 2014
Summary
Understanding acute kidney injury biomarkers requires considering factors like hyperfiltration and nephron number. Our model predicts how different biomarker types respond to injury, aiding clinical interpretation and selection.
Area of Science:
- Nephrology
- Biomarker Research
- Computational Biology
Background:
- Accurate measurement of factors influencing acute kidney injury (AKI) biomarker excretion is challenging.
- Key modifying factors include hyperfiltration, reduced glomerular filtration rate (GFR), structural damage, and nephron number.
Purpose of the Study:
- To model the excretion profiles of different types of AKI biomarkers.
- To investigate the impact of modifying factors on biomarker concentrations.
- To aid in the selection and interpretation of AKI biomarkers in clinical settings.
Main Methods:
- Developed computational models simulating biomarker time-courses in single and multiple nephron scenarios.
- Incorporated pre-formed, induced (upregulated), and filtered biomarker dynamics.
- Modeled three kidney states: healthy, hyperfiltering with reduced nephron number, and chronic kidney disease with reduced GFR and nephron number.
- Simulated AKI scenarios involving structural damage and/or reduced nephron number.
Main Results:
- Pre-formed biomarkers show rapid, transient elevations post-injury, potentially missed clinically.
- Induced biomarker kinetics depend on physiology, insult severity, nephron number, and GFR reduction.
- Filtered biomarkers exhibit longer time-courses due to decreased GFR, with concentration influenced by reabsorption damage and recovery.
- Impaired hyperfiltration significantly elevates biomarker concentrations, particularly in chronic kidney disease.
Conclusions:
- Biomarker choice and interpretation for AKI depend on the timing of insult and pre-existing kidney status.
- Accurate interpretation requires knowledge of pre-insult nephron number (renal mass) and detection of hyperfiltration.
- Modeling provides a framework for understanding biomarker behavior in diverse renal conditions.
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