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The number of patients with end-stage renal disease (ESRD) requiring hemodialysis is increasing worldwide. Although arteriovenous fistula (AVF) is the best and most important vascular access (VA) for hemodialysis, its primary maturation failure rate is as high as 60%, which seriously endangers the prognosis of hemodialysis patients. After AVF establishment, the venous outflow tract undergoes hemodynamic changes, which are translated into intracellular signaling pathway cascades, resulting in an outward and inward remodeling of the vessel wall. Outward remodeling refers to the thickening of the vessel wall and the dilation of the lumen to accommodate the high blood flow in the AVF, while inward remodeling is mainly characterized by intimal hyperplasia. More and more studies have shown that the two types of remodeling are closely related in the occurrence and development of, and jointly determining the final fate of, AVF. Therefore, it is essential to investigate the underlying mechanisms involved in outward and inward remodeling for identifying the key targets in alleviating AVF dysfunction. In this review, we summarize the current clinical diagnosis, monitoring, and treatment techniques for AVF dysfunction and discuss the possible pathological mechanisms related to improper outward and inward remodeling in AVF dysfunction, as well as summarize the similarities and differences between the two remodeling types in molecular mechanisms. Finally, the representative therapeutic targets of potential clinical values are summarized. [ABSTRACT FROM AUTHOR]

Aim: Rhodojaponin VI (R‐VI) is the key compound of Rhododendron molle G. Don (Ericaceae) (RM) with effective clinical application in rheumatoid arthritis and chronic glomerulonephritis. In our study, we tried to explore the effect of R‐VI on the rat model of membranous nephropathy. Methods: The rat model of passive heymann nephritis (PHN) was established by injecting sheep anti‐rat Fx1A serum at a single dose through the tail. The rats were orally administered R‐VI (0.02 mg/kg) or FK506 (1 mg/kg) 1 day before PHN induction, which was kept for 4 weeks. Urine and blood samples as well as kidney tissue were collected for analysis. C5b‐9‐induced human podocyte cell (HPC) was employed for experiments in vitro. Results: R‐VI could alleviate glomerulonephritis progression and podocyte injury in PHN rats, as indicated by the decreased proteinuria and the elevated level of albumin, accompanied with reduced immune deposits, reversed podocyte injury in the kidneys. Furthermore, R‐VI suppressed murine double minute 2 (MDM2) expression without the alteration in the protein level of p53 and decreased Notch1 expression independent of Numb regulation. Pre‐treatment with R‐VI in C5b‐9‐induced HPC blocked MDM2/Notch1 signalling pathway. Conclusion: Thus, R‐VI ameliorates podocyte injury in rats with PHN, which was probably related with MDM2/Notch1 signalling pathway. [ABSTRACT FROM AUTHOR]