Correlation between pre-operative VE-cadherin and DLL4 and the maturation after primary arteriovenous fistula in uremic patients

Abstract

Aims Uremic patients require dialysis to replace the declined kidney function, and arteriovenous fistula (AVF) is a commonly used dialysis access route. Our study aimed to explore vascular endothelial cells cadherin (VE-cadherin) and Delta-like ligand 4 (DLL4) expression in uremic patients undergoing primary AVF surgery and their correlation with AVF maturation. Methods We conducted a prospective study that included n = 55 voluntary uremic patients receiving their initial AVF procedure for renal replacement therapy, subjects were divided into a mature group and a failure group based on whether the AVF matured within 3 months post-operatively. We analyzed the association of VE-cadherin and DLL4 with AVF maturation by examining their expression levels in serum and the endothelium of cephalic veins. Results Pre-operative serum VE-cadherin, in the mature group measured 125.07 (106.77–167.65) ng/L, and DLL4 was 92.78 (83.83–106.72) pg/mL, while the failure group had VE-cadherin at 95.40 (79.03–107.16) ng/L (P = 0.001), and DLL4 at 60.42 (43.98–80.15) pg/mL with a statistical significant; (P = 0.002), binary logistic regression analysis indicated a significant association between cephalic vein diameter, VE-cadherin, DLL4 levels, and AVF immaturity (P = 0.024, P = 0.014 respectively). Immunohistochemical staining showed slightly higher VE-cadherin levels in the mature group than in the failure group (P = 0.366). DLL4 was primarily located in the cell membrane and cytoplasm, concentrated in the inner membrane, with significantly higher levels in the mature group compared to the failure group (P = 0.027). Conclusion The failure group exhibited lower levels of VE-cadherin and DLL4 in serum and vascular tissue, these results suggest that VE-cadherin and DLL4 might play pivotal regulatory roles in the onset and the progression of fistula immaturity, potentially serving as promising targets for future interventions.

Keywords

• Arteriovenous fistula
• Hemodialysis
• Uremia
• VE-cadherin
• Delta-like ligand 4