Abstract
Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.
Highlights
Patent and reliable vascular access is of vital importance to end stage renal disease (ESRD) patients who receive hemodialysis [1] as their choice of renal replacement therapy (RRT)
The aim of this study was to conduct a case-control study to discover whether single nucleotide polymorphism (SNP) of renin-angiotensin-aldosterone system (RAAS) genes (including Angiotensinogen (AGT), Angiotensin converting enzyme gene (ACE), angiotensin II receptor 1 (AGTR1) and 2 (AGTR2)) could be genetic risk factors of Arterio-venous fistula (AVF) thrombosis
The prevalence of diabetes mellitus, cerebrovascular accident, peripheral arterial disease and coronary artery disease did not differ between patients with AVF malfunction and control group (Table 1)
Summary
Patent and reliable vascular access is of vital importance to end stage renal disease (ESRD) patients who receive hemodialysis [1] as their choice of renal replacement therapy (RRT). Arterio-venous fistula (AVF), in comparison with arterio-venous graft (AVG) and tunneled dialysis catheter (TDC), is the best vascular access in terms of higher blood flow rate, lower infection rate, and longer lifespan [2]. The thrombosis and occlusion of AVFs diminish the dialysis adequacy and increase the morbidity and mortality of HD patients [3]. Excessive strength and duration applied on puncture site, insufficient anticoagulation use and infection of vascular access all contribute to the recurrent thrombosis of AVF. Coagulation-related genes, hyperhomocysteinemia-related methylene tetrahydrofolate reductase (MTHFR) gene, transforming growth factor-b1 (TGFB1), matrix metalloproteinases (MMPs), hypoxia inducible factor-1α (HIF1A), heme oxygenase-1 (HO1) and vascular endothelial growth factor-A (VEGFA) and its receptors (FLT1 for VEGFR-1 and KDR for VEGFR-2) have all been studies for their association with AVF stenosis or thrombosis
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