Novel therapeutic targets for cardiorenal syndrome.

Cardiorenal syndrome (CRS) is an interdependent dysfunction of the heart and kidneys, where failure in one organ precipitates failure in the other. The pathophysiology involves sustained renin-angiotensin-aldosterone-system (RAAS) activation, mitochondrial dysfunction, inflammation, fibrosis, oxidative stress and tissue remodeling, culminating in organ dysfunction. Existing therapies targeting the RAAS, diuretics and other agents have limitations, including diuretic resistance and compensatory sodium reabsorption. Therefore, there is a pressing need for novel druggable targets involved in CRS pathogenesis. This review addresses the challenges of existing treatments and emphasizes the importance of discovering new therapeutic targets. It highlights emerging targets such as Klotho, sex-determining region Y box 9 (SOX9), receptor-interacting protein kinase 3 (RIPK3), β-amino-isobutyric acid (BAIBA), thrombospondin-1 (TSP-1), among others, with their potential roles in CRS.