Abstract
Cardiorenal syndrome type 2 is characterized by kidney failure as a consequence of heart failure that affects >50% of heart failure patients. Murine transverse aortic constriction (TAC) is a heart failure model, where pressure overload is induced on the heart without any systemic hypertension or its consequences. Whether renal function is altered in this model is debated, and if so, at which time post-TAC renal dysfunction starts to contribute to worsening of cardiac function. We therefore studied the effects of progressive heart failure development on kidney function in the absence of chronically elevated systemic blood pressure and renal perfusion pressure. C57BL/6J mice (N = 129) were exposed to TAC using a minimally invasive technique and followed from 3 to 70 days post-TAC. Cardiac function was determined with 3D ultrasound and showed a gradual decrease in stroke volume over time. Renal renin expression and plasma renin concentration increased with progressive heart failure, suggesting hypoperfusion of the kidney. In addition, plasma urea concentration, a surrogate marker for renal dysfunction, was increased post-TAC. However, no structural abnormalities in the kidney, nor albuminuria were present at any time-point post-TAC. Progressive heart failure is associated with increased renin expression, but only mildly affected renal function without inducing structural injury. In combination, these data suggest that heart failure alone does not contribute to kidney dysfunction in mice.
Highlights
Cardiorenal syndrome (CRS) is a clinical characterization of patients with both heart and kidney failure where CRS type 2 describes chronic kidney disease (CKD) as consequence of heart failure (Zannad and Rossignol, 2018; Rangaswami et al, 2019)
As the kidneys are downstream of the heart, it is reasonable to assume that they experience hypoperfusion in the transverse aortic constriction (TAC) model, due to a reduced stroke volume
We investigated the relation between renin expression and cardiac function in order to associate the presence of renal hypoperfusion with decreasing stroke volume
Summary
Cardiorenal syndrome (CRS) is a clinical characterization of patients with both heart and kidney failure where CRS type 2 describes chronic kidney disease (CKD) as consequence of heart failure (Zannad and Rossignol, 2018; Rangaswami et al, 2019). A generally accepted model to study adverse cardiac remodeling in heart failure is transverse aortic constriction (TAC). Cardiac remodeling in this model is characterized by early structural changes due to inflammation and fibrosis, and results in left ventricular hypertrophy (Furihata et al, 2016; Gross, 2019). The functional capacity of the heart deteriorates as end systolic and diastolic volumes increase and stroke volume is reduced (Hampton et al, 2017). As the kidneys are downstream of the heart, it is reasonable to assume that they experience hypoperfusion in the TAC model, due to a reduced stroke volume. Little information is available on the progressive deterioration of kidney function in the TAC model, RAS stimulation has been documented to exacerbate heart failure progression after TAC (Rockman et al, 1994; Li et al, 2018)
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