Comorbidities in the Cardiorenal Syndrome

Abstract

A growing number of patients with kidney failure, mainly female, are dealing with a chronic variant of heart failure characterized by a gradual stiffening and impaired relaxation of the heart. Comorbidities, such as obesity, diabetes, and high blood pressure, are often present in these patients and these conditions further affect the progression of concurrent kidney and heart failure. In this thesis, we aimed to gain more insight in how these risk factors affect the development of renal and cardiovascular disease. The importance of recognizing the underlying comorbidities is highlighted as these determine cardiac remodeling, fibrotic and inflammatory dynamics. Interestingly, obesity and hypertension show opposing effects on energy metabolism in the cardiomyocytes. This shows that the existing comorbidities associated with heart failure with impaired relaxation forces the heart to adapt in different ways. In addition, we assess the therapeutic potential of sodium thiosulfate (STS), a hydrogen sulfide metabolite, as a monotherapy or in combination with a blood pressure lowering agent in the experimental setting of hypertensive kidney and heart failure. Promising effects of oral treatment with STS were observed on hypertension, renal and cardiac function and damage but requires further validation in comorbidity-associated kidney and heart failure.