The association between serum indoxyl sulfate and radial-cephalic arteriovenous fistulas dysfunction in ESKD patients: a prospective study.
Elevated serum indoxyl sulfate levels are associated with an increased risk of dysfunction in arteriovenous fistulas used for hemodialysis in chronic kidney disease patients.
Where it sits
this study against the rest of the 5-amino-1mq corpusSummary and findings
This study measured the association between serum indoxyl sulfate (IS) levels and the dysfunction of radial-artery to cephalic-vein arteriovenous fistulas in 113 stage 5 chronic kidney disease patients. After a median follow-up of 12 months, higher serum IS was found in the dysfunction group. Elevated IS and diabetes mellitus were identified as independent risk factors for RCAVF dysfunction.
Abstract
Radial-artery to cephalic-vein end-to-side arteriovenous fistulae (RCAVF) are the first-line vascular access for hemodialysis, yet early stenosis or thrombosis reduces its long-term patency. Indoxyl sulfate (IS), a protein-bound uremic toxin with diverse vascular effects, may impede fistula maturation. We conducted a single-center prospective cohort study enrolling 113 stage 5 chronic kidney disease patients who underwent RCAVF creation between February 2023 and August 2024. Patients were stratified by IS tertiles to assess fistula outcomes. Multivariable Cox regression, Kaplan-Meier analyses, and nomogram construction were used to identify risk factors and patency. Additionally, multiplex tyramide signal amplification immunofluorescence was applied to 40 samples of cephalic vein to quantify aryl hydrocarbon receptor (AHR) and tissue factor (TF) expression. After a median follow-up of 12 months, serum IS was higher in the dysfunction group (<i>p</i> = 0.005). Elevated IS (<i>p</i> = 0.013) and diabetes mellitus (<i>p</i> = 0.006) were independent risk factors for RCAVF dysfunction. Restricted cubic spline analysis showed a linear relationship between IS and risk. Kaplan-Meier curves revealed decreasing primary patency with increasing IS tertiles (<i>p</i> < 0.05), consistent in diabetic patients. The 1-year patency nomogram had good predictive performance (AUC = 0.87). Histopathology showed upregulated AHR and TF expression in veins from dysfunctional fistulas, with correlated fluorescence intensities (<i>r</i> = 0.60, <i>p</i> < 0.05), though neither correlated directly with serum IS (<i>p</i> > 0.05). In conclusion, elevated serum IS independently predicts RCAVF dysfunction, and the aberrant IS-AHR-TF signaling axis may contribute to its pathogenesis.
Background
This paper addresses the impact of serum indoxyl sulfate (IS), a uremic toxin, on the dysfunction of radial-artery to cephalic-vein arteriovenous fistulas (RCAVF), which are critical for hemodialysis access. Prior research has indicated that elevated IS may have adverse vascular effects, but its specific role in RCAVF maturation and patency has not been thoroughly investigated. Understanding these associations is important for improving vascular access outcomes in patients with end-stage kidney disease (ESKD).
Methods
This was a single-center prospective cohort study involving 113 patients with stage 5 chronic kidney disease who underwent RCAVF creation between February 2023 and August 2024. Patients were stratified by IS tertiles to evaluate fistula outcomes, using multivariable Cox regression and Kaplan-Meier analyses. The primary outcome was the patency of the fistula, assessed over a median follow-up of 12 months.
Results
After a median follow-up of 12 months, serum IS was significantly higher in the dysfunction group (p=0.005). Elevated IS (p=0.013) and diabetes mellitus (p=0.006) were identified as independent risk factors for RCAVF dysfunction. Kaplan-Meier analyses indicated a significant decrease in primary patency with increasing IS tertiles (p<0.05). The study also reported a good predictive performance for the 1-year patency nomogram with an AUC of 0.87.
Interpretation
The findings suggest that elevated serum IS levels are associated with an increased risk of RCAVF dysfunction, which aligns with previous literature linking uremic toxins to vascular complications. However, while the statistical significance is clear, the clinical relevance of these findings may be limited by the small sample size and the single-center design. Additionally, the study did not establish a direct correlation between serum IS and the histopathological markers measured, indicating potential confounding factors that could influence the results.
Key findings
- Higher serum IS in dysfunction group, p=0.005.
- Elevated IS was an independent risk factor for RCAVF dysfunction, p=0.013.
- Diabetes mellitus was an independent risk factor for RCAVF dysfunction, p=0.006.
- Kaplan-Meier curves showed decreasing primary patency with increasing IS tertiles, p<0.05.
- 1-year patency nomogram had good predictive performance, AUC = 0.87.
- Correlation between AHR and TF expression in dysfunctional veins, r=0.60, p<0.05.
Limitations
- Single-center study may limit generalizability.
- Potential confounding factors not fully accounted for.
- Small sample size of n=113.
- Short follow-up duration of 12 months.