Renal fibrosis in type 2 cardiorenal syndrome: An update on mechanisms and therapeutic opportunities

Cardiorenal syndrome (CRS) is a state of coexisting heart failure and renal insufficiency in which acute or chronic dysfunction of the heart or kidney lead to acute or chronic dysfunction of the other organ.It was found that renal fibrosis is an important pathological process in the progression of type 2 CRS to end-stage renal disease, and progressive renal impairment accelerates the deterioration of cardiac function and significantly increases the hospitalization and mortality rates of patients. Previous studies have found that Hemodynamic Aiteration, RAAS Overactivation, SNS Dysfunction, Endothelial Dysfunction and Imbalance of natriuretic peptide system contribute to the development of renal disease in the decompensated phase of heart failure, but the exact mechanisms is not clear. Therefore, in this review, we focus on the molecular pathways involved in the devel-opment of renal fibrosis due to heart failure and identify the canonical and non-canonical TGF-beta signaling pathways and hypoxia-sensing pathways, oxidative stress, endoplasmic reticulum stress, pro-inflammatory cy-tokines and chemokines as important triggers and regulators of fibrosis development, and summarize the ther-apeutic approaches for the above signaling pathways, including SB-525334 Sfrp1, DKK1, IMC, rosarostat, 4-PBA, etc. In addition, some potential natural drugs for this disease are also summarized, including SQD4S2, Wogonin, Astragaloside, etc.

Automated summary

Cardiorenal syndrome (CRS) is a condition where heart failure and renal insufficiency coexist, leading to dysfunction in both organs. Renal fibrosis has been identified as a crucial pathological process in the progression of type 2 CRS, causing end-stage renal disease and worsening cardiac function, resulting in high hospitalization and mortality rates. Previous studies have shown that various mechanisms, such as hemodynamic alteration, RAAS overactivation, SNS dysfunction, endothelial dysfunction, and imbalances in natriuretic peptide system, contribute to renal disease development during heart failure, although the exact mechanisms remain unclear. This review focuses on molecular pathways involved in renal fibrosis due to heart failure, highlighting the TGF-beta signaling pathways, hypoxia-sensing pathways, oxidative stress, endoplasmic reticulum stress, pro-inflammatory cytokines, chemokines, and potential therapeutic approaches.