Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies.

Abstract

As the heart and kidneys are closely connected by the circulatory system, primary dysfunction of either organ usually leads to secondary dysfunction or damage to the other organ. These interactions play a major role in the pathogenesis of a clinical entity named cardiorenal syndrome (CRS). The pathophysiology of CRS is complicated and involves multiple body systems. In early studies, CRS was classified into five subtypes according to the organs associated with the vicious cycle and the acuteness and chronicity of CRS. Increasing evidence shows that CRS is associated with a variety of pathological mechanisms, such as haemodynamics, neurohormonal changes, hypervolemia, hypertension, hyperuraemia and hyperuricaemia. In this review, we summarize the classification and currently available diagnostic biomarkers of CRS. We highlight the recently revealed molecular pathogenesis of CRS, such as oxidative stress and inflammation, hyperactive renin‒angiotensin‒aldosterone system, maladaptive Wnt/β-catenin signalling pathway and profibrotic TGF‒β1/Smad signalling pathway, as well as other pathogeneses, such as dysbiosis of the gut microbiota and dysregulation of noncoding RNAs. Targeting these CRS-associated signalling pathways has new therapeutic potential for treating CRS. In addition, various chemical drugs, natural products, complementary therapies, blockers, and agonists that protect against CRS are summarized. Since the molecular mechanisms of CRS remain to be elucidated, no single intervention has been shown to be effective in treating CRS. Pharmacologic therapies designed to block CRS are urgently needed. This review presents a critical therapeutic avenue for targeting CRS and concurrently illuminates challenges and opportunities for discovering novel treatment strategies for CRS.