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Updated: Dec 27, 2025
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Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
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Impaired Tubular Reabsorption Is the Main Mechanism Explaining Increases in Urinary NGAL Excretion Following Acute
Sandra M Sancho-Martínez1,2,3,4,5, Víctor Blanco-Gozalo1,2,3,4, Yaremi Quiros1,2,3,4
1Institute of Biomedical Research of Salamanca (IBSAL).
Summary
Urinary Neutrophil gelatinase-associated lipocalin (NGAL) increases in acute kidney injury (AKI) due to reduced reabsorption, not just shedding. This finding refines NGAL
Area of Science:
- Nephrology
- Biochemistry
- Molecular Biology
Background:
- Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for acute kidney injury (AKI).
- Its overexpression in injured tubular epithelia contributes to its utility.
- Mechanistic insights into urinary NGAL excretion kinetics in AKI require further investigation.
Purpose of the Study:
- To investigate the source and kinetics of urinary NGAL excretion in experimental AKI.
- To differentiate between direct renal shedding and altered tubular handling of NGAL in AKI.
- To refine the interpretation of urinary NGAL measurements for improved clinical utility.
Main Methods:
- Three models of experimental AKI in Wistar rats: ischemia-reperfusion injury (IRI), gentamicin (G), and cisplatin (Cisp) nephrotoxicity.
- Assessment of urinary NGAL excretion rate, plasma NGAL, renal NGAL mRNA/protein expression, and histology.
- In situ renal perfusion studies to determine NGAL source (direct shedding vs. reduced reabsorption).
Main Results:
- Renal NGAL expression and urinary excretion increased in all experimental AKI models.
- Direct renal perfusion eliminated urinary NGAL excretion, indicating reduced reabsorption is a major source.
- Addition of exogenous NGAL or re-establishment of perfusion restored urinary NGAL excretion.
Conclusions:
- Urinary NGAL excretion in AKI primarily results from reduced tubular reabsorption of filtered NGAL.
- Subclinical cellular dysfunction and altered tubular handling significantly impact urinary NGAL levels.
- A more granular interpretation of urinary NGAL measurements can optimize its clinical application as an AKI biomarker.
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