Overview
This article presents a dorsal surgical approach for inducing renal ischemia–reperfusion injury (IRI) in mice, providing a robust and reproducible model for studying the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). The protocol combines unilateral renal IRI with contralateral nephrectomy performed one day prior to sample collection, optimizing both survival and consistency of injury for mechanistic investigations of CKD progression.
Key Study Components
Area of Science
- Nephrology
- Experimental surgery
- Animal models of kidney disease
Background
- Renal IRI is a standard model for studying AKI and its progression to CKD in mice.
- Conventional protocols often compromise either functional assessment or animal survival.
- Existing models struggle to balance reproducibility, injury severity, and long-term survival.
- Reliable models are needed for mechanistic studies of CKD development.
Purpose of Study
- To establish a reproducible and robust mouse model for the AKI-to-CKD transition.
- To minimize variability and maximize survival in renal IRI experiments.
- To enable comprehensive functional and pathological assessment of kidney injury and fibrosis.
Methods Used
- Dorsal surgical approach for kidney access and IRI induction.
- Unilateral renal IRI combined with contralateral nephrectomy performed one day before sample collection.
- Serum-based functional evaluation using BUN and creatinine measurements.
- Histological assessment of interstitial fibrosis via Masson's trichrome staining and CKD marker gene analysis at 28 and 42 days post-injury.
Main Results
- The dorsal approach allows straightforward kidney access and reduces intra-abdominal manipulation.
- Combining unilateral IRI with delayed nephrectomy yields nearly 100% survival and consistent injury severity.
- This protocol avoids the variability of bilateral injury models and the high mortality of early nephrectomy.
- Functional and histological assessments provide complementary insights into kidney impairment and fibrosis development.
Conclusions
- This protocol offers a reliable and versatile mouse model for studying ischemic CKD progression.
- It enables mechanistic investigations by balancing reproducibility, survival, and comprehensive assessment.
- The approach is suitable for long-term studies of kidney injury and fibrosis.
What is the main advantage of the dorsal approach for renal IRI in mice?
The dorsal approach provides straightforward access to the kidneys, minimizes intra-abdominal manipulation, and improves reproducibility and survival rates in renal IRI models.
How does this protocol improve survival compared to traditional models?
By performing contralateral nephrectomy one day prior to sample collection rather than earlier, the protocol achieves nearly 100% survival while maintaining consistent injury severity.
Why is unilateral IRI combined with nephrectomy preferred over bilateral IRI?
Unilateral IRI with nephrectomy reduces variability and avoids the inconsistencies and higher mortality associated with bilateral injury models.
What functional assessments are used in this protocol?
Serum blood urea nitrogen (BUN) and creatinine levels are measured to evaluate kidney function after injury.
How is kidney fibrosis assessed in this model?
Interstitial fibrosis is quantified using Masson's trichrome staining for collagen deposition and analysis of CKD marker gene expression at 28 and 42 days post-injury.
What are the main applications of this mouse model?
This model is ideal for mechanistic studies of the AKI-to-CKD transition, evaluation of therapeutic interventions, and investigation of kidney fibrosis and functional impairment.