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Updated: May 22, 2025
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Development of a Mouse Model of Uremic Cardiomyopathy: Investigating the Impact of Chronic Kidney Disease on Cardiac
Julia Moellmann1, Katja Glandien1, Barbara M Klinkhammer2
1Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
Abstract:
Patients with chronic kidney disease are at an increased risk of developing heart failure, but the underlying mechanisms remain incompletely understood, at least in part because of the paucity of mouse models of uremic cardiomyopathy. In this study, we used two different experimental setups of 2,8-dihydroxyadenine-induced nephropathy in different mouse strains to develop a non-invasive mouse model of uremic cardiomyopathy. Among the different models, only 129/Sv mice fed an adenine-supplemented diet for 16 weeks showed typical features of uremic cardiomyopathy. Kidney damage was confirmed by histopathologic findings of diffuse fibrosis with collagen deposition, crystal formation, and uremia. The cardiac phenotype showed significantly increased myocardial fibrosis associated with impaired cardiac contractility under dobutamine-induced stress conditions. This was associated with a significant activation of the mTOR pathway and downstream endoplasmic reticulum stress, increased apoptosis, and inflammation. Treatment of 129/Sv mice with an adenine-supplemented diet for 16 weeks represents a model of uremic cardiomyopathy with increased myocardial fibrosis and impaired cardiac function, as well as a shift from cardioprotective to detrimental signaling, increased endoplasmic reticulum stress, and inflammation.
Insights
A new mouse model of uremic cardiomyopathy was developed using adenine in 129/Sv mice. This model shows kidney damage, heart fibrosis, and impaired function, aiding research into chronic kidney disease complications.
Area of Science:
- Nephrology
- Cardiology
- Translational Medicine
Background:
- Chronic kidney disease (CKD) patients face a higher risk of heart failure.
- The mechanisms behind uremic cardiomyopathy are not fully understood.
- Existing mouse models for uremic cardiomyopathy are limited.
Purpose of the Study:
- To develop a non-invasive mouse model for studying uremic cardiomyopathy.
- To investigate the cardiac consequences of adenine-induced nephropathy in mice.
Main Methods:
- Two experimental setups of 2,8-dihydroxyadenine-induced nephropathy were used in different mouse strains.
- 129/Sv mice were fed an adenine-supplemented diet for 16 weeks.
- Histopathology and cardiac function assessments were performed.
Main Results:
- 16 weeks of adenine supplementation in 129/Sv mice induced uremic cardiomyopathy.
- Histopathology revealed kidney fibrosis, crystal formation, and uremia.
- Cardiac analysis showed increased myocardial fibrosis and impaired contractility under stress.
- Activated mTOR pathway, endoplasmic reticulum stress, apoptosis, and inflammation were observed.
Conclusions:
- The adenine-fed 129/Sv mouse model effectively replicates uremic cardiomyopathy features.
- This model demonstrates increased myocardial fibrosis, impaired cardiac function, and detrimental signaling pathways.
- It provides a valuable tool for understanding CKD-related heart disease mechanisms.
