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A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Xiaoliang Wang1, Muhammad A Chaudhry2, Ying Nie2
1Marshall Institute for Interdisciplinary Research (MIIR), Marshall University.
Insights
A novel 5/6th partial nephrectomy (PNx) mouse model effectively replicates chronic kidney disease (CKD) and uremic cardiomyopathy. This model shows impaired renal function, anemia, and cardiac dysfunction four weeks post-surgery.
Area of Science:
- Nephrology
- Cardiology
- Experimental Pathology
Background:
- Chronic kidney disease (CKD) significantly increases cardiovascular disease (CVD) risk and mortality.
- CKD progression can lead to uremic cardiomyopathy, a specific cardiac phenotype.
- Existing animal models for studying CKD-induced cardiac dysfunction have limitations.
Purpose of the Study:
- To develop and characterize a novel, efficient surgical mouse model for studying chronic kidney disease (CKD).
- To investigate the development of uremic cardiomyopathy in this new CKD model.
- To assess renal function, anemia, and cardiac parameters in the established model.
Main Methods:
- A two-step surgical procedure was employed: 5/6th partial nephrectomy (PNx) involving ligation of both poles of the left kidney, followed by removal of the right kidney 7 days later.
- Sham surgery was performed as a control, mimicking the surgical steps without kidney manipulation.
- Mice were analyzed four weeks post-surgery to evaluate physiological and pathological changes.
Main Results:
- The PNx model exhibited significantly impaired renal function and anemia compared to sham-operated controls.
- Cardiac hypertrophy and fibrosis were observed in the hearts of PNx mice.
- Significant decreases in both systolic and diastolic cardiac function were detected in the PNx group.
Conclusions:
- The described 5/6th PNx mouse model provides a viable and relatively straightforward method for inducing CKD and uremic cardiomyopathy.
- This model recapitulates key features of human uremic cardiomyopathy, including cardiac structural and functional abnormalities.
- The model is suitable for further research into the mechanisms and potential treatments for CKD-associated cardiovascular complications.
Abstract:
Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy". We describe here an experimental CKD mouse model, named 5/6th partial nephrectomy (PNx) with pole ligation, which developed uremic cardiomyopathy at four weeks post-surgery. This PNx model was performed by a two-step surgery. In step-one surgery, both poles of the left kidney were ligated. In step-two surgery, which was performed 7 days after the step-one surgery, the right kidney was removed. For the sham surgery, the same surgery procedures were performed but without pole ligation of the left kidney or removal of the right kidney. The surgical procedures are easier and less time-consuming, compared to other methods. However, the remnant functional renal mass is not as easily controlled as the renal artery ligation. Four weeks after surgery, in comparison with the sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.
