Hypoxia inducible factors in arteriovenous fistula maturation: A prospective cohort study

Background: Neointimal hyperplasia is the main cause of arteriovenous fistula (AVF) failure. Hypoxia inducible factors (HIFs) factors are associated with neointimal hyperplasia. Thus, we investigated the association between HIF-2 alpha (HIF-2α) and AVF maturation in end stage kidney disease (ESKD) patients.

Methods: This prospective cohort study was conducted in 21 voluntary healthy subjects and 50 patients with ESKD who were eligible for AVF creation. Inclusion criteria were being ESKD patients without a history of AVF surgery and dialysis. 8 patients excluded from the study due to having unavailable veins 6 patients were excluded due to acute thrombosis after surgery. 1 patient lost for follow-up. A total of 35 patients were included in final analysis. The blood samples were collected a day before the AVF surgery for biochemical parameters and HIF-2α measurement. HIF-2α levels measured by the ELISA method.

Results: Compared to healthy subjects, ESKD patients had a significantly higher level of HIF-2α. [1.3(1.0-1.9) vs 2.2(1.6-3.0)] (p=0.002). Patients were divided into two groups after the evaluation of AVF maturation, as the mature group(n=19) and the failure group(n=16). Serum HIF-2α level was 1.7(1.1-1.8) in the mature group however it was 3.1(2.8-3.3 in failure group (p< 0.001). Multiple logistic regression analyses showed that HIF-2α independently predicted AVF maturation. The ROC curve analysis showed that HIF-2α >2.65 predicted AVF maturation failure with the 87% sensitivity and 94% specificity [AUC:0.947, 95% CI (0.815-0.994), p< 0.001].

Conclusions: HIF-2-α levels were higher in ESKD patients than healthy subjects. HIF-2-α could be a marker of AVF maturation failure.

Keywords: Arteriovenous fistula; Hypoxia; Vascular remodeling.