An Integrated Therapeutic Strategy for Cardiorenal Syndrome to Target Oxidative Stress, Inflammation, and Fibrosis

Abstract

Cardiorenal syndrome (CRS) is characterized by a complex, bidirectional interaction between cardiac and renal dysfunction, posing a significant challenge in clinical practice. Although these two organ dysfunctions share common pathophysiological pathways, there remains a major unmet need for therapies that specifically target these shared mechanisms. Oxidative stress, chronic low-grade inflammation, and progressive tissue fibrosis are pivotal, interconnected drivers involved in the progression of both chronic heart failure and chronic kidney disease, constituting a critical pathological triad in CRS. This review aims to systematically elucidate the interplay among reactive oxygen species (ROS), immune cell infiltration, proinflammatory cytokine signaling, and fibrotic pathway activation in the pathogenesis of CRS. We also provide a comprehensive overview of the current landscape of novel pharmacological candidates that target key nodes in the oxidative stress–inflammation–fibrosis axis, including small molecules, biologics, and repurposed drugs. By integrating preclinical evidence with clinical trial data, this review highlights the therapeutic potential of concurrently attenuating oxidative stress, inflammation, and fibrosis to disrupt the vicious cycle of CRS and ultimately improve patient outcomes.