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Updated: Jul 23, 2025
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Cardiorenal damages in mice at early phase after intervention induced by angiotensin II, nephrectomy, and salt intake
Naoto Muromachi1,2, Junji Ishida1, Kazuyuki Noguchi1,3
1Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-8577, Japan.
Abstract:
The interconnection of heart performance and kidney function plays an important role for maintaining homeostasis through a variety of physiological crosstalk between these organs. It has been suggested that acute or chronic dysfunction in one organ causes dysregulation in another one, like patients with cardiorenal syndrome. Despite its growing recognition as global health issues, still little is known on pathophysiological evaluation between the two organs. Previously, we established a preclinical murine model with cardiac hypertrophy and fibrosis, and impaired kidney function with renal enlargement and increased urinary albumin levels induced by co-treatment with vasopressor angiotensin II (A), unilateral nephrectomy (N), and salt loading (S) (defined as ANS treatment) for 4 weeks. However, how both tissues, heart and kidney, are initially affected by ANS treatment during the progression of tissue damages remains to be determined. Here, at one week after ANS treatment, we found that cardiac function in ANS-treated mice (ANS mice) are sustained despite hypertrophy. On the other hand, kidney dysfunction is evident in ANS mice, associated with high blood pressure, enlarged glomeruli, increased levels of urinary albumin and urinary neutrophil gelatinase-associated lipocalin, and reduced creatinine clearance. Our results suggest that cardiorenal tissues become damaged at one week after ANS treatment and that ANS mice are useful as a model causing transition from early to late-stage damages of cardiorenal tissues.
Insights
Early cardiorenal damage occurs within one week of ANS treatment in mice. This preclinical model reveals distinct heart and kidney dysfunction progression, aiding cardiorenal syndrome research.
Area of Science:
- Cardiorenal physiology
- Organ crosstalk
- Preclinical disease modeling
Background:
- The cardiorenal syndrome involves complex interactions between heart and kidney function.
- Understanding the early pathophysiological changes in cardiorenal syndrome is crucial but remains limited.
- Existing models require further characterization of initial organ damage dynamics.
Purpose of the Study:
- To investigate the initial effects of a specific treatment regimen on cardiac and kidney tissues.
- To characterize the early progression of cardiorenal damage in a preclinical model.
- To establish a model for studying the transition from early to late-stage cardiorenal damage.
Main Methods:
- Establishment of a murine model using angiotensin II, unilateral nephrectomy, and salt loading (ANS treatment) for 4 weeks.
- Assessment of cardiac function and histology after one week of ANS treatment.
- Evaluation of kidney function through blood pressure, urinary markers, and creatinine clearance after one week.
Main Results:
- ANS-treated mice exhibited sustained cardiac function despite cardiac hypertrophy after one week.
- Significant kidney dysfunction was observed, including hypertension, glomerular enlargement, increased urinary albumin, and reduced creatinine clearance.
- Urinary neutrophil gelatinase-associated lipocalin levels were elevated, indicating kidney injury.
Conclusions:
- ANS treatment induces detectable cardiorenal tissue damage within one week.
- The developed ANS mouse model effectively captures the transition from early to late-stage cardiorenal damage.
- This model provides a valuable tool for studying the mechanisms and progression of cardiorenal syndrome.
