Effect of Nrf2-Keap1-ARE signaling pathway-related proteins on arteriovenous fistula thrombosis

Abstract

Background:

To analyze the effect of the expression of proteins related to the nuclear factor E2-related factor 2 (Nrf2)-Kelch-like epichlorohydrin-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway on arteriovenous fistula (AVF) thrombosis.

Methods:

One hundred and twenty-two patients with chronic renal failure who underwent maintenance hemodialysis (MHD) at our hospital from October 2019 to March 2023 were selected. Serum Nrf2, Keap1, and ARE expression levels were measured using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and serum oxidative stress markers were determined using chemical colorimetry. Patients were classified into an AVF thrombus group (n = 42) and an AVF patency group (n = 80) based on the presence of AVF thrombosis.

Results:

The relative expression levels of Nrf2, Keap1, and ARE in the AVF thrombus group were significantly lower than those in the AVF patency group (p < 0.05). The levels of SOD and GSH-Px in the AVF thrombus group were lower, while the level of MDA was higher compared to the AVF patency group (p < 0.05). Multivariate Logistic regression analysis identified diabetes mellitus, hypotension, elevated levels of MDA, Hb, and CRP as risk factors for AVF thrombosis (OR > 1, p < 0.05), while elevated levels of Nrf2, Keap1, ARE, SOD, and GSH-Px were protective factors (OR < 1, p < 0.05).

Conclusions:

Patients with AVF thrombosis exhibit low serum Nrf2, Keap1, and ARE expression levels, which is closely associated with oxidative stress. Activating the Nrf2-Keap1-ARE signaling pathway holds promise as a target for the prevention and treatment of AVF thrombosis.