Pre-existing and Postoperative Intimal Hyperplasia and Arteriovenous Fistula Outcomes

Abstract

Background: The contribution of intimal hyperplasia (IH) to arteriovenous fistula (AVF) failure is uncertain. This observational study assessed the relationship between pre-existing, postoperative, and change in IH over time and AVF outcomes.

Study design: Prospective cohort study with longitudinal assessment of IH at the time of AVF creation (pre-existing) and transposition (postoperative). Patients were followed up for up to 3.3 years.

Setting & participants: 96 patients from a single center who underwent AVF surgery initially planned as a 2-stage procedure. Veins and AVF samples were collected from 66 and 86 patients, respectively. Matched-pair tissues were available from 56 of these patients.

Predictors: Pre-existing, postoperative, and change in IH over time.

Outcomes: Anatomic maturation failure was defined as an AVF that never reached a diameter > 6mm. Primary unassisted patency was defined as the time elapsed from the second-stage surgery to the first intervention.

Measurements: Maximal intimal thickness in veins and AVFs and change in intimal thickness over time.

Results: Pre-existing IH (>0.05mm) was present in 98% of patients. In this group, the median intimal thickness increased 4.40-fold (IQR, 2.17- to 4.94-fold) between AVF creation and transposition. However, this change was not associated with pre-existing thickness (r(2)=0.002; P=0.7). Ten of 96 (10%) AVFs never achieved maturation, whereas 70% of vascular accesses remained patent at the end of the observational period. Postoperative IH was not associated with anatomic maturation failure using univariate logistic regression. Pre-existing, postoperative, and change in IH over time had no effects on primary unassisted patency.

Limitations: The small number of patients from whom longitudinal tissue samples were available and low incidence of anatomic maturation failure, which decreased the statistical power to find associations between end points and IH.

Conclusions: Pre-existing, postoperative, and change in IH over time were not associated with 2-stage AVF outcomes.

Keywords: AVF creation; AVF transposition; Intimal hyperplasia (IH); anatomic maturation failure; arteriovenous fistula (AVF); end-stage renal disease (ESRD); failure; hemodialysis; histology; intimal thickness; outcomes; primary unassisted patency; stenosis; vascular access; vascular pathology.

Fig 1

Flow diagram of the study design illustrating sample collection, exclusion criteria, and subsequent histopathological and statistical analysis.

Fig 2. Pre-existing intimal hyperplasia (IH) in veins

Representative basilic veins with low (A–C) and high pre-existing IH (D–I). The intimal thickness in first-stage veins oscillated between 0 to 0.66 (median, 0.18) mm (n=57). Intimal thickness was measured in Masson’s trichrome stained sections (A, D, G). A significant number of intimal cells in the pre-fistula vein were smooth muscle cells that stained positive for α-smooth muscle cell actin (B, E, H) and smooth muscle myosin heavy chain (C, F, I). Microphotographs in G, H and I correspond to magnifications of boxed areas in D, E and F, respectively. I = Intima, M = Media.

Fig 3. Association between pre-existing intimal hyperplasia and primary unassisted patency

Kaplan-Meier curves for AVF with pre-existing intimal thickness above and below the group median of 0.20 mm after excluding anatomic maturation failures (n=52). Fistulas classified as anatomic maturation failure underwent a short transposition or graft extension and, therefore, had to be excluded from the analysis.

Fig 4. Intimal hyperplasia (IH) in matched pairs of veins and AVF

A–B. Representative matched tissue pair of a basilic vein (A) and AVF (B) collected before anastomosis and superficialization of a two-stage AVF from the same patient. Sections were Masson’s trichrome stained. C. Matched pair analysis showing the change in intimal thickness in AVF with respect to the corresponding vein. AVF with anatomic maturation failure are shown in red. D–E. High magnification pictures of boxed areas in A-B, highlighting the media thickness and loss of smooth muscle cells (SMC) in the AVF. Arrows point to SMC stained in red. I = Intima, M = Media. F. Fold changes in medial and intimal thickness in AVF versus veins. G–H. Changes in the intima (G) and media (H) during remodeling. The relative areas of SMC (red) and collagen (blue) were quantified on Masson’s trichrome stained sections. P values were calculated using a two-sample paired t-test with unequal variances. I. Linear regression analysis demonstrating the lack of correlation between pre-existing and postoperative IH in matched pairs.

Fig 5. Association between postoperative intimal hyperplasia and anatomic maturation failure

Representative sections of mature (A–C) and failed AVF (D–F). Sections were Masson’s trichrome stained. The maximal intimal thickness is marked with a yellow arrow.

Fig 6. Association between postoperative and change in intimal hyperplasia (IH) with primary unassisted patency

A. Kaplan-Meier curves for AVF with postoperative intimal thickness above and below the group’s median (0.57 mm, N=69). B. Kaplan-Meier curves for AVF with change in intimal thickness above and below the group’s median (0.36 mm, N= 46).