1 Introduction

National Kidney Foundation (NKF) Kidney Dialysis Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines recommend Arteriovenous fistulas (AVFs) for establishing dialysis access in patients with end-stage renal failure [1]. Stenosis, a common threat to dialysis access patency, can lead to the dysfunction of mature AVFs. Conventionally, percutaneous procedures typically entail either making a venous puncture of the fistula for lesion access and subsequent treatment with balloon angioplasty, in managing stenosis. However, the effectiveness of this approach diminishes when dealing with lesions positioned distal to the puncture site, multiple concurrent lesions involving also the venous outflow, and multiple side branches between the anastomosis and venous access with poorly depiction of the afferent radial artery despite tourniquet application above the venous access site [2-4].

Hence, while venous outflow is the favored choice for vascular access, scenarios exist where arterial access becomes valuable [3, 4]. The arterial access can be established either proximal or distal to the anastomosis site. In particular, adopting a downstream transradial access (TRA) approach offers several advantages. It enables the concurrent treatment of multiple stenoses, some of which might also affect the venous outflow. Additionally, it provides a means to address juxta-anastomotic lesions, especially when there's complex venous anatomy involved. It also simplifies the performance of comprehensive angiography, providing a clear visualization of the entire AVF tract. Moreover, it helps safeguard the arterial inflow against potential complications originating from the vascular access site as opposed to brachial artery access [2, 5, 6].

In recent years, the utilization of TRA in endovascular procedures has garnered significant attention due to its array of benefits compared to traditional transfemoral access. These advantages encompass rapid recovery, a reduced incidence of severe hemorrhagic events, diminished vascular complications, lower rates of adverse cardiovascular events and mortality, ease of hemostasis, and a higher level of patient satisfaction [7-11]. TRA has proven to be effective for the endovascular management of dialytic fistulas as well, since its first description by Wang et al. for interventions on Brescia-Cimino fistulas [2-4].

However, despite these recognized advantages, there remains a paucity of research examining the comparative safety and efficacy of TRA in contrast to venous outflow access for the endovascular management of malfunctioning AVFs. This study is designed to evaluate the effectiveness, feasibility and safety of radial access for the endovascular management of AVFs. Furthermore, it aims to directly compare the efficacy, feasibility and safety data associated with TRA and venous outflow access, addressing the current dearth of comprehensive information in the existing body of literature.

2 Methods

2.4 Statistical Analysis

Data were maintained in an Excel spreadsheet (Microsoft Inc, Redmond, Wash) and the statistical analyses were performed using SPSS software (SPSS, version 22 for Windows; SPSS Inc, Chicago IL, USA). Our analysis focused on the Modified Intention-To-Treat population, encompassing all randomized patients who had received at least one endovascular intervention [26, 27]. Kolmogorov-Smirnov test and Shapiro-Wilk test were used to verify the normality assumption of data [28]. Categorical data are presented as frequency (percentage value) [29]. Continuous normally distributed data are presented as mean ± standard deviation. Continuous not normally distributed data are presented as median (interquartile range: 25th and 75th percentiles—IQR) [30, 31]. The unpaired Student t-test, the Chi-squared/Fisher's exact test, and the Mann-Whitney test were respectively used to assess statistical differences for continuous normally distributed, categorical and continuous not normally distributed data, as appropriate and previously described [32, 33]. Patients’ data were censored at the conclusion of the follow-up period, which extended until November 30, 2023, or a duration of 12 months after the intervention, or at the point of study discontinuation, or when a malfunctioning fistula was definitively abandoned, or in the unfortunate event of a patient's demise. Kaplan-Meier survival analysis was used to evaluate time-dependent outcomes, and the log-rank test was employed to make comparisons. To ensure the independence of censored data from the events being tested, clinical assessments and telephone contacts were conducted in cases of study withdrawal. As a result, the assumption of independent censoring was met, mitigating any potential bias associated with the observed time-dependent data. A P-value of < 0.05 was considered statistically significant for the abovementioned tests.

3 Results

3.4 Survival Analysis

By Kaplan-Meier survival analysis, primary patency rates were 95.2% (±0.03 SE) at 1 month, 75.8% (±0.05 SE) at 6 months and 48.4% (±0.06 SE) at 12 months in TRA group. Primary patency rates were 94.4% (±0.02 SE) at 1 month, 77.8% (±0.03 SE) at 6 months and 41.7% (±0.04 SE) at 12 months in TVA group. Assisted-primary patency rates were 95.2% (±0.03 SE) at 1 month, 88.7% (±0.04 SE) at 6 months and 48.4% (±0.06 SE) at 12 months in TRA group. Assisted-primary patency rates were 94.4% (±0.02 SE) at 1 month, 86.1% (±0.03 SE) at 6 months and 41.7% (±0.04 SE) at 12 months in TVA group. Secondary patency rates were 95.2% (±0.03 SE) at 1 month, 88.7% (±0.04 SE) at 6 months and 61.1% (±0.06 SE) at 12 months in TRA group. Secondary patency rates were 94.4% (±0.02 SE) at 1 month, 87.5% (±0.03 SE) at 6 months and 62.4% (±0.04 SE) at 12 months in TVA group. The median primary patency wasn't significantly different between TRA group (12 months, CI: NA-NA) and TVA group (11 months, CI: 9.6-12.4), according to the Log-Rank test (p = 0.469). For patients undergoing TRA, the median (CI) assisted-primary patency was 12 (NA-NA) months, similar to that of patients undergoing TVA (12 [11.5–12.5] months) (p = 0.477, calculated by mean of Log-Rank test). The median secondary patency wasn't significantly different between TRA group (12 months, CI: NA-NA) and TVA group (12 months, CI: NA-NA), according to the Log-Rank test (p = 0.863) Table 4.

Table 4. Time-dependent outcomes assessed by Kaplan-Meier survival analysis..

	Cumulative Rates	At 1 month rate (±SE)—numbers at risk	At 6 months rate (±SE)—numbers at risk	At 12 months rate (±SE)—numbers at risk
	Primary patency TRA	95.2% (±0.03) - 59	75.8% (±0.05) - 47	48.4% (±0.06) - 30
	Primary patency TVA	94.4% (±0.02) - 136	77.8% (±0.03) - 112	41.7% (±0.04) - 60
	Assisted-primary patency TRA	95.2% (±0.03) - 59	88.7% (±0.04) - 55	48.4% (±0.06) - 30
	Assisted-primary patency TVA	94.4% (±0.02) - 136	86.1% (±0.03) - 124	41.7% (±0.04) - 60
	Secondary patency TRA	95.2% (±0.03) - 59	88.7% (±0.04) - 55	61.1% (±0.06) - 37
	Secondary patency TVA	94.4% (±0.02) - 136	87.5% (±0.03) - 126	62.4% (±0.04) - 88

4 Discussion

TRA is widely employed in the field of endovascular interventions, including the management of dysfunctional dialytic fistulas [2, 4, 19, 34, 35]. Rahmatzadeh et al. observed a 100% technical success rate in 30 interventions performed via TRA for endovascular management of dysfunctional dialytic AVF. A technical success rate of 95.3% was noted in an investigation by Ong et al. on a large cohort of patients from Singapore, despite smaller radial artery diameters than Western population [2]. Wang et al. enrolled 50 dysfunctional Brescia-Cimino fistulas and 69 target lesions in their study, with only a case of TRA technical failure due to intense RAS after failed radial artery puncture and five cases of residual stenosis greater than 30% (namely, 91.3% technical success rate) [3]. Technical and clinical success rates of 98.6% and 91.7%, respectively, were noted by Choi et al. following angioplasty of 73 malfunctioning AVFs [36]. The NKF KDOQI guidelines specify a minimum access flow rate of 500 mL/min to ensure effective dialysis [1]. In our study, all patients exhibited a significant improvement in access flow rate, ensuring effective dialysis (namely, 100% clinical success rate). These results are consistent with a few other reports on TRA, such as those by Mohiuddin et al. and Ong et al. [2, 37]. Kawarada et al. reported 100% technical and clinical success rates in their case-series on 50 radiocephalic fistulas treated by TRA [4].

While it is common practice to consider venous outflow as the primary vascular access site [38] and to use TRA in specific clinical scenarios for the endovascular management of malfunctioning dialytic fistulas [5], there is a notable lack of studies that have directly compared TVA and TRA. The efficacy of TRA procedures may be constrained by the presence of narrow radial artery diameters, thus preventing the use of larger caliber catheters [39]. Our study's results indicate that both TVA and TRA routes are associated with high rates of technical and clinical success. Furthermore, the direct comparison did not reveal statistically significant differences between the two groups, thus making TRA equally effective to TVA for endovascular management of malfunctioning dialytic fistulas. Hence, TRA access should be considered in specific challenging clinical scenarios. Firstly, in the presence of multiple stenoses that also affect the venous outflow, as selecting an appropriate transvenous access site can be complex in such instances, potentially necessitating a distant puncture near the axilla. Secondly, in cases involving complex venous anatomy and stenoses, TRA allows for the effortless execution of arterial inflow angiography, ensuring a clear visualization of the entire fistula conduit and enhanced maneuverability of the guide within the intricate network of veins (e.g., as seen in the Gracz fistula where the perforating vein of the median antebrachial vein is anastomosed with the proximal radial artery) [40, 41]. Thirdly, in situations where the transvenous approach fails to traverse tight stenoses (e.g., 65% technical success rate reported for peripheral occlusion of radiocephalic fistulas addressed with TVA) [3, 42]. Lastly, it is important to take into account that applying hemostasis directly to the venous outflow fistula can increase the risk of fistula thrombosis, particularly when the outcomes of percutaneous transluminal angioplasty (PTA) are suboptimal [3].

Another viable approach is the transbrachial access, which has been evaluated in comparison with the TRA by Shamimi-Noori et al. In a cohort of 56 patients undergoing endovascular interventions for nonmaturing AVFs, the subgroup subjected to TRA exhibited fewer access site punctures, higher rates of clinical and technical success, superior primary patency, and improved assisted primary patency at 12 months [17].

While the assessment of short- and medium-term patency is not the primary focus of this study, the recorded data align with findings from other research within the realm of endovascular management of AVFs. Rahmatzadeh et al. recorded a 32.8% primary patency rate and a 63.3% assisted primary patency rate at 12 months, in a cohort of 30 patients undergoing endovascular management of malfunctioning fistulas with TRA [5]. Ong et al. observed a poor primary patency rate of 19.5% at 12 months in patients from Singapore [2]. Evaluations of PTA for dialysis access interventions involving the customary TVA method indicate a spectrum of primary patency rates at the 6-month mark, spanning from 50% to 70%, as documented in existing studies [43].

In the case series on TRA by Rahmatzadeh et al., 46.7% patients required an upgrade to a 6-Fr sheath for the final intervention [5]. In our study, the rate of upgrading to an introducer with a minimum diameter of six French was relatively low compared to earlier studies. Several factors may contribute to this trend, including the limited number of cases involving multiple stenoses including central venous ones, the exclusion of isolated central venous stenoses and the technological advancements that have allowed the use of low-profile larger caliber PTA balloons compatible with five French introducers (e.g., Sterling balloon catheter, Boston Scientific Corporation, Natick, MA). Moreover, the feasibility of TRA is underscored by the absence of significant differences in procedural time between the TRA and TVA groups in our experience. Consequently, our findings suggest that TRA did not entail a significant procedural time extension compared to TVA. This observation might be explained by the fact that, despite TRA being associated with a longer cannulation time, the ease of performing an angiography from the arterial inflow potentially facilitates quicker visualization and swifter crossing of target stenoses. Lastly, our findings align with other reports on fistuloplasty using TRA, which have documented average procedural times of approximately 30–50 min [2, 3, 44, 45].

In our investigation, all VASCs remained clinically inconsequential and were managed with noninvasive therapies. Specifically, cases of RAS and RAO were pharmacologically treated, while effective resolution of access site hematomas and post-fistuloplasty venous ruptures was achieved through prolonged compression. The rate of vascular access site complications (VASCs) was comparable to other published studies in the endovascular field, whether it is femoral or radial access [46-56]. Shamini-Noori et al. also found a significantly lower rate of complications in the TRA group compared to the transbrachial access group for percutaneous management of nonmaturing AVFs [17]. The occlusion of the radial artery represents one of the most concerning complications associated with TRA, with its incidence ranging from 1% to 10% [57]. This risk has been further mitigated by the growing adoption of distal radial access in clinical practice [20, 47, 58, 59]. The incidence of clinically significant RAO is quite rare, primarily owing to the anastomoses between the ulnar and radial arteries [57, 60]. Rahmatzadeh et al. described two cases (6.7%) of RAO with good supply to the palmar arch by patent ulnar arteries; no clinically-significant VASCs were noted [5]. In a recent investigation on 43 fistuloplasties with TRA by Ong et al., a 9.3% rate of RAO was noted and all instances were managed conservatively [2]. Kawarada et al. didn't observe any cases of RAO in their series on 50 radiocephalic fistulas treated by TRA [4]. In our case series, only one instance of radial artery occlusion has been recorded, which remained clinically inconsequential thanks to the robust ulnar artery supply, a factor consistently assessed through the Barbeau Test before every TRA procedure [12]. Additionally, it can be speculated that the low rate of RAO observed in our study is influenced by the ultrasound assessment of vascular caliber adequacy before each TRA [61], the US-guided puncture [5], the substantial expertise of operators in performing TRA procedures [62], the use of thin-walled sheaths [63] as well as catheters and guides with hydrophilic coating [64], the administration of spasmolytic cocktail after introducer sheath positioning [13, 65], the adoption of a patent hemostasis technique [66], and the reduced application time of the hemostatic device [67]. Therefore, TRA was not associated with a significantly higher rate of VASCs in comparison to TVA, and no clinically significant VASCs were noted, in keeping with previous evidence. The use of TRA appears to be a safe option for the endovascular management of malfunctioning dialytic fistulas.

It is essential to underscore certain anatomical limitations of the TRA approach. A minority of patients may have a radial artery caliber measuring less than 2 mm, making the use of the radial access site inadvisable [61]. Another anatomical constraint associated with TRA is its inability to accommodate larger caliber introducers. The need to upgrade to larger caliber introducers may arise in the presence of central venous stenoses, thromboses addressed with thrombectomy device or when deploying covered stents for vascular ruptures. In certain instances, the radial artery's diameter permits the placement of eight French introducers, albeit at the cost of an elevated risk of vascular injury and RAO [68, 69]. The inability to navigate across the arteriovenous anastomosis from a TRA can occur due to variant anatomical factors, such as a radial loop, acute angulation at the anastomosis, a high origin of the radial artery, or stenosis [17, 20, 48]. The TRA may have limitations when dealing with arterio-venous anastomoses that are extremely distal and positioned close to the radial access site. In such situations, it can be beneficial to explore the option of a distal TRA, typically within the anatomical snuffbox region [17, 70]. Interestingly, an atypical origin of the radial artery was previously noted in 8.3% patients undergoing TRA [71].

The retrospectivity of the analysis and the non-randomized fashion are the main limitations of our study. Another notable limitation is the extensive experience of our operators in TRA procedures. It is well-established that TRA necessitates a learning curve, and vascular access site complications are less frequent in centers with greater TRA utilization [62]. Thus, it is plausible that the low VASC rate observed may, in part, be influenced by operator expertise. Consequently, our findings may not be readily generalizable to centers with limited TRA experience. Another limitation stems from the substantial influence of methodological aspects on the safety of TRA. Indeed, the meticulous attention to numerous procedural details may have significantly contributed to the reduction of VASCs, thus rendering the findings of our study less applicable to clinical scenarios lacking this level of methodological rigor. The criteria for selecting TRA differed from those for TVA, potentially introducing a selection bias. Patient allocation was not randomized but rather based on operator preferences endorsed in multidisciplinary discussions. Addressing this bias analytically could be achieved through propensity score matching, which requires treatment group assignment to depend on observable variables. However, in our case, assignment is contingent upon operator preferences, which are not observable variables and cannot be quantified as covariates. Nevertheless, we do not believe this has impacted the outcomes of our study, given that our operators employ TRA in specific clinical scenarios, which are inherently more challenging than the typical TVA. Consequently, the effectiveness associated with TRA should be diminished rather than enhanced by these criteria. The measurement of secondary patency did not differentiate the reasons for AVF abandonment; thus, it was not recorded how many AVFs were specifically abandoned due to thrombosis. However, no cases of outflow thrombosis were recorded as complications related to the performed endovascular procedure. Lastly, an assessment of long-term results was not conducted.

5 Conclusions

To the best of our knowledge, no study has directly compared the effectiveness, feasibility, and safety of TRA with TVA for the endovascular management of malfunctioning dialysis fistulas.

Our report highlights remarkably high rates of both technical and clinical success with TRA, which are akin and comparable to standard TVA. The feasibility of TRA is optimal when considering non-prolonged procedural times and infrequent instances of conversion to another vascular access or upgrading to a six French introducer or larger. TRA stands as a secure vascular approach widely embraced in clinical practice, and it demonstrates no statistically significant increase in clinically relevant VASCs when compared to TVA. While venous outflow remains the standard vascular access site for managing malfunctioning dialysis fistulas, TRA can prove highly effective and safe in certain challenging clinical scenarios.

Conflicts of Interest

The authors declare no conflicts of interest.

Ethics Statement

Ethics committee approval was not required due to the retrospective nature of the study. The study has been conducted in accordance with the Helsinki Declaration. All patients signed a written informed consent before receiving the endovascular treatment.