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Updated: Mar 23, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Myocardial dysfunction occurs prior to changes in ventricular geometry in mice with chronic kidney disease (CKD)
Pamela D Winterberg1, Rong Jiang2, Josh T Maxwell3
1Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia Children's Heart Research & Outcomes (HeRO) Center, Children's Healthcare of Atlanta & Emory University, Atlanta, Georgia pdwinte@emory.edu.
Insights
Early detection of uremic cardiomyopathy in chronic kidney disease (CKD) is possible using ventricular strain analysis. This method identifies myocardial dysfunction before structural changes occur, aiding in predicting heart failure progression.
Area of Science:
- Cardiology
- Nephrology
- Biomedical Engineering
Background:
- Uremic cardiomyopathy significantly increases morbidity and mortality in chronic kidney disease (CKD) patients.
- The mechanisms driving uremic cardiomyopathy are not fully understood.
- Ventricular strain analysis shows promise in predicting adverse outcomes in CKD patients.
Purpose of the Study:
- To investigate early myocardial dysfunction in a mouse model of CKD using ventricular strain analysis.
- To determine if ventricular strain analysis can detect cardiac changes preceding hypertrophy in CKD.
Main Methods:
- CKD was induced in mice via partial nephrectomy (5/6Nx).
- Serial transthoracic echocardiography and invasive hemodynamic measurements were performed.
- Gene expression and histology analyzed cardiac tissue at 8 and 16 weeks.
Main Results:
- CKD mice exhibited decreased longitudinal strain and diastolic dysfunction by 2 weeks post-surgery.
- Ventricular hypertrophy was observed later, at 4 weeks.
- Progressive cardiac fibrosis and elevated natriuretic peptide expression were noted, indicative of heart failure.
Conclusions:
- Early myocardial dysfunction, detectable by ventricular strain analysis, precedes geometric changes in CKD-induced cardiomyopathy.
- This mouse model demonstrates progressive fibrosis and heart failure markers, validating its use for studying uremic cardiomyopathy.
Abstract:
Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD), but the underlying mechanisms contributing to this complex phenotype are incompletely understood. Myocardial deformation analyses (ventricular strain) of patients with mild CKD have recently been reported to predict adverse clinical outcome. We aimed to determine if early myocardial dysfunction in a mouse model of CKD could be detected using ventricular strain analyses. CKD was induced in 5-week-old male 129X1/SvJ mice through partial nephrectomy (5/6Nx) with age-matched mice undergoing bilateral sham surgeries serving as controls. Serial transthoracic echocardiography was performed over 16 weeks following induction of CKD. Invasive hemodynamic measurements were performed at 8 weeks. Gene expression and histology was performed on hearts at 8 and 16 weeks. CKD mice developed decreased longitudinal strain (-25 ± 4.2% vs. -29 ± 2.3%; P = 0.01) and diastolic dysfunction (E/A ratio 1.2 ± 0.15 vs. 1.9 ± 0.18; P < 0.001) compared to controls as early as 2 weeks following 5/6Nx. In contrast, ventricular hypertrophy was not apparent until 4 weeks. Hearts from CKD mice developed progressive fibrosis at 8 and 16 weeks with gene signatures suggestive of evolving heart failure with elevated expression of natriuretic peptides. Uremic cardiomyopathy in this model is characterized by early myocardial dysfunction which preceded observable changes in ventricular geometry. The model ultimately resulted in myocardial fibrosis and increased expression of natriuretic peptides suggestive of progressive heart failure.
