Intimal hyperplasia is defined as the presence of cells and fibrous tissue between the endothelium and internal elastic lamina [17]. The radial and internal thoracic arteries are commonly used as conduits in CABG. However, because the radial artery has a higher incidence of intimal hyperplasia than the internal thoracic artery, the internal thoracic artery is now more commonly used [17]. The incidence of intimal hyperplasia of the radial artery varies. Allon et al. [34] reported that among 50 ESRD patients, none of the arteries obtained at the time of AVF creation had intimal hyperplasia. However, others reported values of 56% to 100% [16,23,35,36]. It is unclear why the incidence of intimal hyperplasia varies among studies. The diagnostic criteria for intimal hyperplasia, degree of renal failure, age, race, and primary renal disease (e.g., DM) might play a role in the variable incidence of intimal hyperplasia. Chitalia et al. [9] reported that the intima thickness was increased in 10 brachial arteries and seven radial arteries of pre-dialysis and dialysis patients compared to controls. Johansson et al. [17,19] used high-resolution ultrasound to examine the intimal and medial thicknesses in ESRD and healthy subjects. The intima and media in ESRD patients were 39% and 18%, respectively, thicker than those in healthy subjects. The incidence of intima hyperplasia was 76.3% to 94% in patients with mild-to-moderate renal insufficiency and coronary artery disease. Other risk factors for intimal hyperplasia are old age, DM, hypertension, and cardiovascular disease [23,37]. Because most ESRD patients have these risk factors, they are expected to show frequent intimal hyperplasia of the radial artery.

There are only two studies on the relationship between AVF patency and intimal hyperplasia of the radial artery [21,34]. We evaluated the degree of intimal hyperplasia of the radial artery by histologic examination in 59 ESRD patients undergoing radiocephalic AVF creation [21]. The patients were followed for up to 1 year for AVF patency. AVF failure was defined as complete obstruction of the AVF or blood flow insufficient to support a dialysis blood flow rate of ≥ 200 mL/min. The AVF failure rate within 1 year in patients with intimal hyperplasia was higher than that in those without intimal hyperplasia. The intima in the failed AVF group was thicker than that in the patent group (93.1 ± 37.5 mm vs. 45.6 ± 17.4 mm, p < 0.001). In contrast, Allon et al. [34] reported that AVF patency was not related to radial artery intimal hyperplasia. None of 50 patients had intimal hyperplasia. Another study [36] reported that the mean intima thickness of the radial artery was 12.5 mm in 73 ESRD patients undergoing an arteriovenous graft operation, which is thinner than in our work; the reason for this discrepancy is unknown. We suggest that demographic differences such as ethnicity, age, sex, and underlying disease, and differences in radial artery size led to the discrepant results in terms of the severity and frequency of intimal hyperplasia. In the above study [36], most of the patients were African-American, and patients with a minimum radial artery diameter of 2 mm were included. Our study included only Koreans, and venous mapping was not performed before the operations. The selection of vascular access was determined based on the surgeon’s clinical experience. As a result, our study might have included smaller-diameter radial arteries. Chowdhury et al. [19] reported that the frequency of intimal hyperplasia was higher in small radial arteries. Therefore, the incidence and severity of intimal hyperplasia was higher and greater, respectively, in our work than in Allon's data [34,36]. Tripathi et al. [38] reported that the mean intima thickness of the radial artery was 49.9 mm in 32 Indian ESRD patients, which is similar to our result. However, there was a limitation that the entire circumferential arterial wall could not be acquired during AVF. Intimal hyperplasia was evenly distributed throughout the wall of the radial artery in a study involving CABG, in which circumferential artery samples were obtained [17,19]. In addition to arterial intimal hyperplasia, pathologic changes in veins are important as venous stenosis is related to AVF patency. In conclusion, AVF patency is determined by the incidence and severity of pre‑existing intimal hyperplasia of the radial artery.

Several factors play a role in arterial micro-calcification (AMiC) in ESRD patients. Hypercalcemia, hyperphosphatemia, dyslipidemia, hypertension, DM, and uremic toxin induce vascular calcification [41,42]. This leads to osteoblastic conversion of vascular smooth muscle cells [43]. The process is facilitated by decreased levels of inhibitors of vascular calcification such as fetuin A, matrix Gla protein, osteopontin, osteoprotegerin, and pyrophosphate. Along with uremic toxin, oxidative stress and inflammation, which are commonly found in ESRD patients, are involved in vascular calcification [41,42]. Shroff et al. [44] demonstrated that dialysis accelerates AMiC by triggering smooth muscle cell apoptosis. AMiCs are found in different layers depending on the artery in question. Intimal calcification occurs in atherosclerosis, which is associated with atherosclerotic plaques and lipid accumulation. Clinically, intimal calcification results in stenotic lesions such as ischemic heart disease and cerebrovascular accidents [41,42]. In contrast, medial calcification is commonly observed in arteriosclerosis. It increases arterial stiffening, leading to left ventricular hypertrophy and congestive heart failure [41,42]. AMiC in the radial artery of ESRD patients is usually found in the medial area and can be detected by von Kossa staining. The incidence of AMiC in the radial or brachial artery is 36% to 54.5% [45-49].

Three studies have evaluated the effect of AMiC on AVF patency. We performed von Kossa staining to detect pre-existing AMiC in ESRD patients undergoing AVF, and followed up AVF failure for 1 year [47]. Preoperative vascular mapping was not performed. Of the patients, 65.8% had DM and 80.7% (n = 75) had a radiocephalic AVF (n = 92). Of 114 patients, AMiC was found in 37.7%. Patients with AMiC (n = 43) showed a higher AVF failure rate than patients without AMiC (n = 71). Allon et al. [34] reported that the incidence of AMiC (n = 47) was not related to maturation failure in 50 ESRD patients (79% vs. 68%, p = 0.6). However, a higher maturation failure rate was related to a high AMiC score, which represents calcification severity (1.3 ± 0.8 vs. 0.9 ± 0.8, p = 0.08). In another study, Allon et al. [48] assessed the relationship between AMiC and AVF patency in 127 ESRD patients. They performed preoperative vascular mapping, and the study population comprised 46.6% (n = 59) patients with DM and 34.6% (n = 44) with a radiocephalic AVF, which are lower proportions than in our study. The incidence of AMiC was 40%, which is similar to our result. In contrast to our findings, AMiC was not correlated with non-maturation and unassisted primary failure. Allon et al. [36] data showed the opposite results from our findings, possibly for the same reason as the intimal hyperplasia results. Besides the difference in ethnicity, our study included more DM patients and more patients with a radiocephalic AVF, and we did not perform preoperative vascular mapping, relying instead on the surgeon’s clinical experience to select the vascular access operation site. Consequently, more calcified radial arteries would be included in our study. Georgiadis et al. [50] assessed the effect of radial artery gross calcification on primary and secondary AVF patency rates by plain X-ray in DM patients before radiocephalic AVF. Patients with gross calcification (n = 39) showed lower primary and secondary AVF patency rates than those without gross calcification (n = 33). This suggests that the severity of pre-existing gross calcification affects radiocephalic AVF patency. Further study is expected in the future.