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Updated: Jun 23, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Cardiac structure and function in a mouse model of uraemia without hypertension
Susanne Bro1, Entela Bollano, Annemarie Brüel
1Department of Nephrology, Rigshospitalet, Copenhagen, Denmark. susannebro@dadlnet.dk
Insights
Uremia does not directly harm the heart in mice lacking hypertension. Kidney dysfunction
Area of Science:
- Nephrology
- Cardiology
- Uremic toxicity
Background:
- Kidney dysfunction is linked to heart problems and increased cardiovascular mortality.
- It remains unclear if uremia directly affects the heart or if hypertension is the primary driver.
Purpose of the Study:
- To investigate the direct impact of uremia on cardiac structure and function, independent of hypertension.
- To determine the role of hypertension in the development of left ventricular disease associated with uremia.
Main Methods:
- Apolipoprotein-E (apoE)-deficient mice, resistant to hypertension, underwent 5/6 nephrectomy (NX) or sham operation (Sh).
- Mice were treated with enalapril (an ACE inhibitor) or no medication to assess the effects of uremia with and without hypertension.
- Cardiac structure, function, fibrosis, and gene expression were evaluated 36 weeks post-nephrectomy.
Main Results:
- Nephrectomy (NX) induced uremia but did not increase blood pressure in apoE-deficient mice.
- NX did not alter cardiac structure, left ventricular mass, fibrosis, or cardiac function.
- Enalapril reduced blood pressure and cardiac mass in both NX and sham groups, but did not improve cardiac function.
Conclusions:
- Uremia alone does not appear to impair cardiac structure or function in this mouse model.
- The findings suggest that hypertension plays a crucial role in the development of left ventricular disease in the context of kidney dysfunction.
Unlabelled:
Kidney dysfunction is often associated with cardiac left ventricular hypertrophy and increased cardiovascular mortality.
Objective:
The aim of this study was to find out whether this reflects direct effects of uraemia on the heart or is dependent on accompanying hypertension.
Material And Methods:
Apolipoprotein-E (apoE)-deficient C57BL/6 mice are resistant to development of hypertension after renal mass reduction. To evaluate the impact of uraemia without hypertension on the heart, apoE-deficient mice underwent 5/6 nephrectomy (NX) or sham operation (Sh) and were randomized to treatment with the angiotensin converting enzyme inhibitor enalapril (12 mg kg(-1) d(-1)) or no medication.
Results:
NX did not affect systolic blood pressure (BP), but reduced mean creatinine clearance, body weight and blood haemoglobin to 27% (p < 0.01), 82% (p < 0.0001) and 73% (p < 0.0001), respectively, of the values in Sh mice. Thirty-six weeks after NX, heart wet weight, echocardiographic estimates of left ventricular mass and left ventricular diastolic and systolic functions were similar in NX and Sh mice. NX did not increase cardiac fibrosis or cardiac mRNA expression of biglycan, whereas it decreased the mRNA expression of procollagen (p < 0.01). Enalapril reduced BP (p < 0.001), heart wet weight and estimated left ventricular mass in both NX (p < 0.01) and Sh mice (p < 0.05), but did not affect cardiac diastolic or systolic function. Conclusions. The results suggest that uraemia does not impair cardiac structure or function in apoE-deficient mice. Since NX has no effect on BP in apoE-deficient mice, the results may indicate that hypertension is important for development of left ventricular disease in uraemia.
