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Updated: May 18, 2026
An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury
Published on: July 15, 2021
Ischemia/reperfusion-induced renal failure in rats as a model for evaluating cell therapies
Hung-Jen Wang1, Adam Varner, Tamer AbouShwareb
1Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Abstract:
Chronic renal failure is a devastating disease that leads to a multitude of complications. Cell therapy has emerged as a potential treatment modality for renal failure. However, efficacy testing on systemic renal function has been challenging due to the limited availability of reliable models that are fully characterized. In this study, we investigated the possibility of using renal ischemia/reperfusion (I/R) injury as a viable model for testing cell therapies. We examined functional and pathological changes in rat kidneys that were exposed to different ischemia times. Male Lewis rats were divided into five groups. Renal failure was induced by clamping both renal pedicles for combinations of 60, 75, and 90 min, followed by reperfusion. Age-matched healthy rats served as controls. Blood was collected at regular intervals for serum chemistry, and kidneys were harvested at the same intervals for histomorphological assessment. Serum creatinine levels of the animals with I/R injury increased significantly after 3 days and returned to normal levels at 4 weeks. Histologically, kidney tissue showed progressive glomerular and tubular deterioration with varying degrees of fibrosis. Animals exposed to 75- and 90-min ischemia combination times consistently generated more severe injury than the 60-min ischemia period. However, these groups resulted in a high mortality rate. A model in which one kidney is exposed to a shorter ischemia time (60 or 90 min) resulted in sustained renal damage with a lower mortality rate. This study shows that kidneys exposed to I/R result in renal tissue damage as well as decreased renal function. This model can be used to study both the short-term and longer-term effects of kidney disease by varying the length of the ischemic time. In particular, the use of longer ischemic times (75 and 90 min) could be used to study new therapies for acute renal disease, whereas shorter ischemic times (60 min) could be used to study therapies for chronic renal insufficiency.
Insights
This study demonstrates that renal ischemia/reperfusion (I/R) injury in rats effectively models chronic kidney disease. Varying ischemic times allows for testing cell therapies for both acute and chronic renal failure.
Area of Science:
- Nephrology
- Regenerative Medicine
- Surgical Research
Background:
- Chronic kidney disease presents significant challenges in treatment and research.
- Cell therapy offers potential for renal failure treatment, but reliable efficacy models are scarce.
- Renal ischemia/reperfusion (I/R) injury is explored as a potential model for cell therapy testing.
Purpose of the Study:
- To evaluate the utility of renal ischemia/reperfusion (I/R) injury as a model for testing cell therapies.
- To characterize functional and pathological changes in rat kidneys following varying durations of I/R.
- To establish a reproducible model for studying acute and chronic kidney disease.
Main Methods:
- Male Lewis rats underwent induced renal failure via bilateral renal pedicle clamping for 60, 75, or 90 minutes, followed by reperfusion.
- Serum creatinine levels and kidney histomorphology were assessed at regular intervals post-injury.
- Control groups consisted of age-matched healthy rats.
Main Results:
- I/R injury significantly increased serum creatinine levels, returning to normal by 4 weeks.
- Histological analysis revealed progressive glomerular and tubular damage with fibrosis.
- Longer ischemia times (75-90 min) caused more severe injury but higher mortality; shorter times (60 min) induced sustained damage with lower mortality.
Conclusions:
- Renal I/R injury in rats effectively recapitulates renal tissue damage and functional decline seen in kidney disease.
- The I/R model allows for investigation of both short-term (acute) and long-term (chronic) effects of renal insults.
- This model is suitable for evaluating cell therapies for acute renal disease (longer ischemia) and chronic renal insufficiency (shorter ischemia).
