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.

Peritoneal dialysis (PD) serves as a home-based kidney replacement therapy with increasing utilization across the globe. However, long-term use of high-glucose-based PD solution incites repeated peritoneal injury and inevitable peritoneal fibrosis, thus compromising treatment efficacy and resulting in ultrafiltration failure eventually. In the present study, we utilized human mesothelial MeT-5A cells for the in vitro experiments and a PD mouse model for in vivo validation to study the pathophysiological mechanisms underneath PD-associated peritoneal fibrosis. High-glucose PD solution (Dianeal 4.25%, Baxter) increased protein expression of mesothelial–mesenchymal transition (MMT) markers, such as N-cadherin and α-SMA in MeT-5A cells, whereas it decreased catalase expression and stimulated the production of reactive oxygen species (ROS). Furthermore, macrophage influx and increased serum pro-inflammatory cytokines, such as IL-1β, MCP-1, and TNF-α, were observed in the PD mouse model. Interestingly, we discovered that oligo-fucoidan, an oligosaccharide extract from brown seaweed, successfully prevented PD-associated peritoneal thickening and fibrosis through antioxidant effect, downregulation of MMT markers, and attenuation of peritoneal and systemic inflammation. Hence, oligo-fucoidan has the potential to be developed into a novel preventive strategy for PD-associated peritoneal fibrosis.