Development of cardiac alterations in a rat model of polycystic kidney disease

Introduction Polycystic kidney disease is associated with an increased cardiovascular risk in humans. Hypertrophy and impaired relaxation of the heart can be early signs of cardiac dysfunction even with preserved ejection fraction (EF). Objective The aim of the study was to evaluate cardiac alterations in rats with polycystic kidney (PCK). Particularly, the chronological sequence of renal and cardiac damages was assessed. Methods PCK and control rats were studied at 3, 6, and 9 months of age. Renal function was determined with the level of plasma creatinine and urea. Arterial pressure, cardiac hypertrophy (weight), cardiac fibrosis (Sirius red staining), cardiac functional parameters E/A and E/E’ were performed by cardiac echography. Cardiac expression of cardiokines were analyzed by RT-qPCR to investigate the secretory heart function and the signalization implicated in the cardiac alteration. Results At 9 mo., PCK rats exhibited elevated plasma creatinine and urea, increased arterial pressure, and higher heart weight index. Cardiac fibrosis was higher in PCK rats, increased with time, and was doubled compared to controls at the age of 9 months. Both E/A and E/E’ were reduced in 9 mo. PCK rats while ejection fraction was preserved. Expression of Apelin was reduced and GDF15 was increased at this time. At 6 months of age, kidney function and ejection fraction were maintained. Yet, E/A and E/E’ were already altered despite no significant elevation of cardiac mass and fibrosis. In addition, cardiokines profile was also modified at 6 mo. At the age of 3 months, none of the parameters studied was different in PCK compared to control rats. Conclusion Diastolic function was modified before the clear reduction of renal function and cardiac ejection fraction. On the other hand, when renal function began to degrade there was an acceleration of alterations of cardiac function and cardiokines profile coupled with development of moderate arterial hypertension.