Magnitude of Urine Albumin and KIM-1 Changes Can be Used to Differentiate Glomerular Injury From Tubular Injury in Rats

Emerging urinary kidney safety biomarkers have been evaluated in recent years and have been shown to be superior to the serum parameters blood urea nitrogen (BUN) and creatinine (sCr) for monitoring kidney injury in the proximal tubule. However, their potential application in differentiating the loc...

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Bibliographic Details
Published in:Toxicologic pathology 2024-02, Vol.52 (2-3), p.88-98
Main Authors: Gu, Yi-Zhong, Paul, Erina, Vlasakova, Katerina, Troth, Sean P., Sistare, Frank D., Ramaiah, Lila, Potz, Oliver, Sutradhar, Santosh, Glaab, Warren E.
Format: Article
Language:English
Subjects:
Acute Kidney Injury - pathology
Acute Kidney Injury - urine
Albumins - analysis
Albumins - metabolism
Albuminuria
Algorithms
Animals
Biomarkers - blood
Biomarkers - urine
Cell Adhesion Molecules
Hepatitis A Virus Cellular Receptor 1 - analysis
Kidney Glomerulus - pathology
Kidney Tubules - pathology
Male
Original
Rats
Rats, Sprague-Dawley
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Summary:Emerging urinary kidney safety biomarkers have been evaluated in recent years and have been shown to be superior to the serum parameters blood urea nitrogen (BUN) and creatinine (sCr) for monitoring kidney injury in the proximal tubule. However, their potential application in differentiating the location of the initial kidney injury (eg, glomerulus vs tubule) has not been fully explored. Here, we assessed the performance of two algorithms that were constructed using either an empirical or a mathematical model to predict the site of kidney injury using a data set consisting of 22 rat kidney toxicity studies with known urine biomarker and histopathologic outcomes. Two kidney safety biomarkers used in both models, kidney injury molecule 1 (KIM-1) and albumin (ALB), were the best performers to differentiate glomerular injury from tubular injury. The performance of algorithms using these two biomarkers against the gold standard of kidney histopathologic examination showed high sensitivity in differentiating the location of the kidney damage to either the glomerulus or the proximal tubules. These data support the exploration of such an approach for use in clinical settings, leveraging urinary biomarker data to aid in the diagnosis of either glomerular or tubular injury where histopathologic assessments are not conducted.
ISSN:0192-6233
1533-1601
1533-1601
DOI:10.1177/01926233241248656