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Updated: Jun 16, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Performance of novel kidney biomarkers in preclinical toxicity studies
Dana Hoffmann1, Melanie Adler, Vishal S Vaidya
1Department of Toxicology, University of Würzburg, Würzburg, Germany.
Abstract:
The kidney is one of the main targets of drug toxicity, but early detection of renal damage is often difficult. As part of the InnoMed PredTox project, a collaborative effort aimed at assessing the value of combining omics technologies with conventional toxicology methods for improved preclinical safety assessment, we evaluated the performance of a panel of novel kidney biomarkers in preclinical toxicity studies. Rats were treated with a reference nephrotoxin or one of several proprietary compounds that were dropped from drug development in part due to renal toxicity. Animals were dosed at two dose levels for 1, 3, and 14 days. Putative kidney markers, including kidney injury molecule-1 (Kim-1), lipocalin-2 (Lcn2), clusterin, and tissue inhibitor of metalloproteinases-1, were analyzed in kidney and urine using quantitative real-time PCR, ELISA, and immunohistochemistry. Changes in gene/protein expression generally correlated well with renal histopathological alterations and were frequently detected at earlier time points or at lower doses than the traditional clinical parameters blood urea nitrogen and serum creatinine. Urinary Kim-1 and clusterin reflected changes in gene/protein expression and histopathological alterations in the target organ in the absence of functional changes. This confirms clusterin and Kim-1 as early and sensitive, noninvasive markers of renal injury. Although Lcn2 did not appear to be specific for kidney toxicity, its rapid response to inflammation and tissue damage in general may suggest its utility in routine toxicity testing.
Insights
Novel kidney biomarkers, including clusterin and kidney injury molecule-1 (Kim-1), detect early renal damage in preclinical toxicity studies. These noninvasive markers show promise for improved drug safety assessment.
Area of Science:
- Toxicology
- Biomarker Discovery
- Preclinical Research
Background:
- Kidney toxicity is a significant concern in drug development, often detected late.
- Early detection of renal damage is crucial for preclinical safety assessment.
- Combining omics technologies with traditional toxicology can enhance safety evaluations.
Purpose of the Study:
- To evaluate novel kidney biomarkers for early detection of drug-induced renal toxicity.
- To assess the performance of biomarkers like Kim-1, Lcn2, clusterin, and TIMP-1 in preclinical models.
- To compare novel biomarkers against traditional parameters like blood urea nitrogen and serum creatinine.
Main Methods:
- Rats were administered a nephrotoxin or proprietary compounds at two dose levels for 1, 3, or 14 days.
- Kidney and urine samples were analyzed for gene/protein expression of biomarkers using qPCR, ELISA, and immunohistochemistry.
- Histopathological alterations and traditional clinical parameters were assessed.
Main Results:
- Biomarker changes correlated with histopathological findings and were often detected earlier or at lower doses than traditional markers.
- Urinary clusterin and Kim-1 reflected renal injury without significant functional changes, confirming their sensitivity.
- Lcn2 showed rapid response to inflammation/tissue damage, suggesting broader utility.
Conclusions:
- Clusterin and Kim-1 are validated as early, sensitive, noninvasive biomarkers for renal injury.
- Novel biomarkers offer improved early detection of nephrotoxicity in preclinical settings.
- Lcn2 may serve as a general indicator of inflammation and tissue damage in toxicity testing.
