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Updated: May 14, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Subtotal nephrectomy accelerates pathological cardiac remodeling post-myocardial infarction: implications for
Shan Liu1, Andrew R Kompa, Sirinart Kumfu
1Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
Insights
Myocardial infarction (MI) followed by 5/6 nephrectomy (STNx) in rats worsened cardiac dysfunction and accelerated kidney fibrosis. This study supports bidirectional cardiorenal syndrome interactions and offers a model for therapy assessment.
Area of Science:
- Cardiovascular and Renal Physiology
- Pathophysiology of Cardiorenal Syndrome
Background:
- Concomitant cardiac and renal dysfunction is a complex clinical challenge.
- Understanding the pathophysiology of cardiorenal syndrome (CRS) is crucial for effective treatment.
Purpose of the Study:
- To investigate the molecular, structural, and functional changes in the heart and kidney following a sequential insult of myocardial infarction (MI) and 5/6 nephrectomy (STNx).
- To establish an animal model that mimics the bidirectional interactions observed in cardiorenal syndrome.
Main Methods:
- Male Sprague Dawley rats underwent either sham surgery or MI, followed by sham surgery or STNx four weeks later.
- Cardiac and renal function, hemodynamics, and cardiac/renal tissue were assessed at baseline and post-intervention.
- Groups included Sham+Sham, MI+Sham, Sham+STNx, and MI+STNx.
Main Results:
- Sequential STNx post-MI significantly accelerated left ventricular ejection fraction decline and increased cardiac remodeling markers (e.g., heart/lung weight ratios, myocyte size, fibrosis).
- MI in the presence of STNx exacerbated renal tubulointerstitial fibrosis compared to STNx alone.
- Gene expression analysis revealed increased markers of cardiac stress and fibrosis in the MI+STNx group.
Conclusions:
- The study demonstrates a clear bidirectional interaction between cardiac and renal insults, where MI accelerates cardiac dysfunction and STNx exacerbates renal fibrosis.
- This experimental model provides a valuable platform for evaluating therapeutic strategies targeting cardiorenal syndrome.
Background:
To further understand the pathophysiology of concomitant cardiac and renal dysfunction, we investigated molecular, structural and functional changes in heart and kidney that occur when a kidney insult (5/6 nephrectomy-STNx) follows myocardial infarction (MI).
Methods:
Male Sprague Dawley rats (n=43) were randomized into four groups: Sham-operated MI+Sham-operated STNx (Sham+Sham), MI+Sham-operated STNx (MI+Sham), Sham-operated MI+STNx (Sham+STNx) and MI+STNx. MI/Sham surgery was followed by STNx/Sham surgery 4 weeks later. Cardiac and renal function was assessed prior to STNx/Sham surgery and again 10 weeks later. Hemodynamic parameters were measured prior to sacrifice.
Results:
Compared to the MI+Sham group, STNx further accelerated the reduction in left ventricular (LV) ejection fraction by 21% (p<0.01), and increased tau logistic by 38% (p<0.01) in MI+STNx animals. Heart weight/body weight (BW) and lung weight/BW ratios were 39% (p<0.001) and 16% (p<0.01) greater in MI+STNx compared to MI+Sham animals. Similarly, myocyte cross-sectional area (p<0.001), cardiac interstitial fibrosis (p<0.01) and collagen I (p<0.01) were increased in the LV non-infarct zone of the myocardium in the MI+STNx group. These changes were associated with significant increases in atrial natriuretic peptide (p<0.001), transforming growth factor β1 (p<0.05) and collagen I (p<0.05) gene expression in MI+STNx animals. In comparison with the Sham+STNx group, renal tubulointerstitial fibrosis was increased by 64% in MI+STNx animals (p<0.001), with no further deterioration in renal function.
Conclusions:
STNx accelerated cardiac changes post-MI whilst MI accelerated STNx-induced renal fibrosis, supporting bidirectional interactions in cardiorenal syndrome (CRS). This animal model may be of use in assessing the impact of therapies to treat CRS.
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