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Updated: Aug 1, 2025
Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
Liquid Biopsies Poorly miRror Renal Ischemia-Reperfusion Injury
Adaysha C Williams1, Vaishali Singh2, Pengyuan Liu1
1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Abstract:
Acute kidney injury (AKI) is the rapid reduction in renal function. It is often difficult to detect at an early stage. Biofluid microRNAs (miRs) have been proposed as novel biomarkers due to their regulatory role in renal pathophysiology. The goal of this study was to determine the overlap in AKI miRNA profiles in the renal cortex, urine, and plasma samples collected from a rat model of ischemia-reperfusion (IR)-induced AKI. Bilateral renal ischemia was induced by clamping the renal pedicles for 30 min, followed by reperfusion. Urine was then collected over 24 h, followed by terminal blood and tissue collection for small RNA profiling. Differentially expressed (IR vs. sham) miRs within the urine and renal cortex sample types demonstrated a strong correlation in normalized abundance regardless of injury (IR and sham: R2 = 0.8710 and 0.9716, respectively). Relatively few miRs were differentially expressed in multiple samples. Further, there were no differentially expressed miRs with clinically relevant sequence conservation common between renal cortex and urine samples. This project highlights the need for a comprehensive analysis of potential miR biomarkers, including analysis of pathological tissues and biofluids, with the goal of identifying the cellular origin of altered miRs. Analysis at earlier timepoints is needed to further evaluate clinical potential.
Insights
Early detection of acute kidney injury (AKI) is challenging. This study found limited overlap in microRNA (miRNA) biomarkers between rat kidney tissue and urine, suggesting a need for comprehensive analysis to identify reliable AKI diagnostics.
Area of Science:
- Biochemistry
- Molecular Biology
- Nephrology
Background:
- Acute kidney injury (AKI) is a critical condition characterized by rapid renal function decline, often detected late.
- Biofluid microRNAs (miRNAs) are investigated as potential biomarkers for AKI due to their regulatory roles in kidney pathophysiology.
- Early and accurate detection of AKI remains a significant clinical challenge.
Purpose of the Study:
- To investigate the overlap of microRNA (miRNA) profiles in the renal cortex, urine, and plasma of a rat model with ischemia-reperfusion (IR)-induced AKI.
- To assess the potential of urinary and plasma miRNAs as non-invasive biomarkers for AKI.
- To identify common and differentially expressed miRNAs across different sample types in AKI.
Main Methods:
- Induction of bilateral renal ischemia in rats for 30 minutes, followed by reperfusion.
- Collection of urine over 24 hours post-reperfusion.
- Small RNA sequencing of renal cortex, urine, and plasma samples for miRNA profiling.
Main Results:
- A strong correlation was observed in normalized miRNA abundance between urine and renal cortex samples, irrespective of injury status (R² = 0.8710 for IR, R² = 0.9716 for sham).
- A limited number of miRNAs were differentially expressed across multiple sample types (renal cortex, urine, plasma).
- No differentially expressed miRNAs with significant sequence conservation were found common to both renal cortex and urine samples.
Conclusions:
- While urinary and renal cortex miRNA profiles show correlation, the limited overlap in differentially expressed miRNAs suggests challenges in using them as direct biomarkers for AKI.
- Comprehensive analysis of pathological tissues and biofluids is crucial for identifying the cellular origin of altered miRNAs.
- Further investigation at earlier time points is necessary to fully evaluate the clinical potential of miRNA biomarkers for AKI.
