Related Experiment Video
Updated: May 27, 2026
5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
Subtotal nephrectomy plus coronary ligation leads to more pronounced damage in both organs than either nephrectomy or
Lennart G Bongartz1, Jaap A Joles, Marianne C Verhaar
1Department of Cardiology, University Medical Center Utrecht, Utrecht.
Insights
Pre-existing chronic kidney disease (CKD) exacerbates heart damage after myocardial infarction, and heart failure (HF) worsens kidney disease. This study models cardiorenal syndrome, revealing combined damage and reduced nitric oxide availability.
Area of Science:
- Cardiology
- Nephrology
- Physiology
Background:
- The coexistence of chronic kidney disease (CKD) and heart failure (HF) is linked to adverse patient outcomes.
- Understanding the interplay between CKD and HF is crucial for managing cardiorenal syndrome.
Purpose of the Study:
- To investigate whether pre-existing CKD worsens cardiac outcomes following myocardial infarction (MI).
- To determine if subsequent HF exacerbates CKD progression.
- To establish a novel rat model for studying combined CKD and HF.
Main Methods:
- Subtotally nephrectomized (SNX) rats and sham-operated controls (CON) underwent coronary ligation (CL) or sham surgery.
- Cardiac hemodynamics, renal function, and end-organ damage were assessed.
- Mortality and urinary nitric oxide (NO) metabolite excretion were measured.
Main Results:
- The SNX + CL group exhibited more severe glomerulosclerosis than SNX alone, despite lower blood pressure.
- Cardiac dilatation and reduced ejection fraction were more pronounced in SNX + CL compared to CON + CL post-MI.
- SNX + CL showed impaired diastolic function, decreased myocardial arteriolar diameter, and lower urinary NO metabolites.
Conclusions:
- Combined CKD and HF result in greater cardiac and renal damage than individual conditions, independent of systemic hemodynamics.
- Reduced nitric oxide availability may be a key factor linking worsened kidney function and cardiac diastolic dysfunction in cardiorenal syndrome.
Abstract:
Coexistence of chronic kidney disease (CKD) and heart failure (HF) in humans is associated with poor outcome. We hypothesized that preexistent CKD worsens cardiac outcome after myocardial infarction, and conversely that ensuing HF worsens progression of CKD. Subtotally nephrectomized (SNX) or sham-operated (CON) rats were subjected to coronary ligation (CL) or sham surgery in week 9 to realize four groups: CON, SNX, CON + CL, and SNX + CL. Blood pressure and renal function were measured in weeks 8, 11, 13, and 15. In week 16, cardiac hemodynamics and end-organ damage were assessed. Blood pressure was significantly lower in SNX + CL vs. SNX. Despite this, glomerulosclerosis was more severe in SNX + CL vs. SNX. Two weeks after CL, SNX + CL had more cardiac dilatation compared with CON + CL (end-diastolic volume index: 0.28 ± 0.04 vs. 0.19 ± 0.03 ml/100 g body wt; mean ± SD, P < 0.001), although infarct size was similar. During follow-up in SNX + CL, ejection fraction declined. Mortality was only observed in SNX + CL (2 out of 9). In SNX + CL, end-diastolic pressure (18 ± 4 mmHg) and tau (29 ± 9 ms), the time constant of active relaxation, were significantly higher compared with SNX (13 ± 3 mmHg, 20 ± 4 ms; P < 0.01) and CON + CL (11 ± 5 mmHg, 17 ± 2 ms; P < 0.01). The diameter of small arterioles in the myocardium was significantly decreased in SNX + CL vs. CON + CL (P < 0.01). Urinary excretion of NO metabolites was significantly lower in SNX + CL compared with both CL and SNX. This study demonstrates the existence of more heart and more kidney damage in a new model of combined CKD and HF than in the individual models. Such enhanced damage appears to be separate from systemic hemodynamic changes. Reduced nitric oxide availability may have played a role in both worsened glomerulosclerosis and cardiac diastolic function and appears to be a connector in the cardiorenal syndrome.
