Candidate Gene Analysis of Arteriovenous Fistula Failure in Hemodialysis Patients

Abstract

Arteriovenous fistula (AVF) failure remains an important cause of morbidity in hemodialysis patients. The exact underlying mechanisms responsible for AVF failure are unknown but processes like proliferation, inflammation, vascular remodeling, and thrombosis are thought to be involved. The current objective was to investigate the association between AVF failure and single nucleotide polymorphisms (SNPs) in genes related to these pathophysiologic processes in a large population of incident hemodialysis patients. A total of 479 incident hemodialysis patients were included between January 1997 and April 2004. Follow-up lasted 2 years or until AVF failure, defined as surgery, percutaneous endovascular intervention, or abandonment of the vascular access. Forty-three SNPs in 26 genes, related to proliferation, inflammation, endothelial function, vascular remodeling, coagulation, and calcium/phosphate metabolism, were genotyped. Relations were analyzed using Cox regression analysis. In total, 207 (43.2%) patients developed AVF failure. After adjustment, two SNPs were significantly associated with an increased risk of AVF failure. The hazard ratio (95% confidence interval) of LRP1 rs1466535 was 1.75 (1.15 to 2.66) and patients with factor V Leiden had a hazard ratio of 2.54 (1.41 to 4.56) to develop AVF failure. The other SNPs were not associated with AVF failure. In this large cohort of hemodialysis patients, only 2 of the 43 candidate SNPs were associated with an increased risk of AVF failure. Whether other factors, like local hemodynamic circumstances, are more important or other SNPs play a role in AVF failure remains to be elucidated.