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

Abstract

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 development of renal fibrosis due to heart failure and identify the canonical and non-canonical TGF-β signaling pathways and hypoxia-sensing pathways, oxidative stress, endoplasmic reticulum stress, pro-inflammatory cytokines and chemokines as important triggers and regulators of fibrosis development, and summarize the therapeutic 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.

Keywords: Cardiorenal syndrome; Endoplasmic reticulum stress; Hypoxia-sensing pathways; Inflammation; Oxidative stress; Renal fibrosis.