Clinical and histopathological predictors of secondary arteriovenous fistula failure due to intimal hyperplasia

Intimal hyperplasia (IH) is an important pathological mechanism underlying secondary arteriovenous fistula (AVF) failure in previously mature fistulas, yet the clinical and histopathological determinants that distinguish progressive IH leading to access loss from stable IH remain poorly characterized. This study aimed to identify clinical and histopathological predictors of secondary AVF failure due to IH in previously mature fistulas, and to develop a predictive nomogram for risk stratification.

This retrospective cohort study enrolled 320 patients with end-stage renal disease (ESRD) who underwent AVF creation between January 2020 and June 2025 and had histopathologically confirmed IH from surgical specimens. Patients were classified into a secondary failure group (n = 142, previously mature AVFs permanently abandoned due to IH-driven dysfunction) and a secondary patency group (n = 178) based on access outcomes. Clinical, laboratory, hemodynamic, and histopathological variables were compared between groups. Multivariable logistic regression was performed to identify independent predictors. A nomogram was constructed and internally validated using bootstrap resampling (1,000 iterations).

Multivariable analysis identified seven independent predictors of secondary AVF failure: diabetes mellitus (OR = 2.31, 95% CI: 1.42-3.76, P = 0.001), C-reactive protein ≥ 8.0 mg/L (OR = 1.89, 95% CI: 1.18-3.03, P = 0.008), intima-to-media thickness ratio > 1.5 (OR = 3.67, 95% CI: 2.18-6.17, P < 0.001), CD68⁺ macrophage density > 25 cells/HPF (OR = 2.54, 95% CI: 1.53-4.22, P < 0.001), α-SMA positive area > 40% (OR = 2.12, 95% CI: 1.31-3.43, P = 0.002), MMP-9 high expression (OR = 1.95, 95% CI: 1.21-3.14, P = 0.006), and neovascularization density > 15 vessels/HPF (OR = 1.78, 95% CI: 1.09-2.91, P = 0.021). The nomogram demonstrated good discrimination (C-index = 0.847, 95% CI: 0.803-0.891) and calibration. Decision curve analysis confirmed superior net clinical benefit compared with individual predictors.

Integration of clinical parameters and histopathological markers enables accurate prediction of secondary AVF failure due to IH. The proposed nomogram may facilitate individualized risk stratification and guide clinical decision-making regarding vascular access management in hemodialysis patients.