Related Experiment Video
Updated: May 17, 2026
An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury
Published on: July 15, 2021
Toxicogenomic biomarkers for renal papillary injury in rats
Takeki Uehara1, Chiaki Kondo, Yuji Morikawa
1Drug Developmental Research Laboratories, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan. takeki.uehara@shionogi.co.jp
Abstract:
Renal papillary injury is a common side effect observed during nonclinical and clinical investigations in drug development. The present study aimed to identify genomic biomarkers for early and sensitive detection of renal papillary injury in rats. We hypothesized that previously identified genomic biomarkers for tubular injury might be applicable for the sensitive detection of papillary injury in rats. We selected 18 genes as candidate biomarkers for papillary injury based on previously published studies and analyzed their expression profiles by RT-PCR in each kidney region, namely the cortex, cortico-medullary junction, and papilla in various nephrotoxicity models. Comparative analysis of gene expression profiles revealed that some genes were commonly upregulated or downregulated in the renal papilla, reflecting papillary injuries induced by 2-bromoethylamine hydrobromide, phenylbutazone, or n-phenylanthranilic acid. By applying receiver operator characteristics analysis, six candidate biomarkers were identified and their usefulness was confirmed by using an independent data set. The three top-ranked genes, Timp1, Igf1, and Lamc2, exhibited the best prediction performance in an external data set with area under the curve (AUC) values of greater than 0.91. An optimized support vector machine model consisting of three genes achieved the highest AUC value of 0.99. In conclusion, even though definitive validation studies are required for the establishment of their usefulness and reliability, these identified genes may prove to be the most promising candidate genomic biomarkers of renal papillary injury in rats.
Insights
Researchers identified novel genomic biomarkers for early detection of renal papillary injury in rats. Top candidates like Timp1, Igf1, and Lamc2 show high accuracy in predicting kidney damage.
Area of Science:
- Toxicology
- Genomics
- Drug Development
Background:
- Renal papillary injury is a frequent adverse effect in drug development.
- Early and sensitive detection methods are crucial for patient safety.
Purpose of the Study:
- To identify genomic biomarkers for early and sensitive detection of renal papillary injury in rats.
- To evaluate the applicability of known tubular injury biomarkers for papillary injury detection.
Main Methods:
- Analysis of 18 candidate gene expression profiles using RT-PCR in different rat kidney regions.
- Utilized receiver operator characteristic (ROC) analysis to identify predictive biomarkers.
- Validated biomarker performance using an independent dataset and machine learning models.
Main Results:
- Several genes were commonly upregulated or downregulated in the renal papilla, indicating papillary injury.
- Six candidate biomarkers were identified, with Timp1, Igf1, and Lamc2 showing the highest predictive performance (AUC > 0.91).
- An optimized support vector machine model using three genes achieved an AUC of 0.99.
Conclusions:
- Identified genes, particularly Timp1, Igf1, and Lamc2, are promising genomic biomarkers for renal papillary injury in rats.
- Further validation studies are necessary to establish their clinical utility and reliability.
- These biomarkers could significantly improve early detection of drug-induced kidney damage.
