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Selection Committee Member: Monnie Wasse @wasse_m

Haimanot (Monnie) Wasse is Professor and Vice Chairperson in the Department of Internal Medicine at Rush University Medical Center. She is also the Director of Interventional Nephrology and recently completed a 2-year tenure as the President of the American Society of Diagnostic and Interventional Nephrology. Her research focuses on the predictors, consequences and treatment of arteriovenous access dysfunction. She seeks to characterize the key mechanisms, pathways, and genes involved in dialysis access dysfunction, particularly in the high-risk populations.

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Writer: Swapnil Hiremath @hswapnil

Swapnil Hiremath is an Associate Professor at the University of Ottawa and an Associate Scientist at the Ottawa Hospital Research Institute. His primary clinical and research interests are in improving care of individuals living with high blood pressure, CKD, and those receiving hemodialysis. He is co-founder of the online nephrology journal club, #NephJC.

Competitors for the HD Access Region

Percutaneous AVF Creation vs Surgical AVF Creation

EU Guidelines vs American Guidelines

Copyright: mailsonpignata / Shutterstock

Percutaneous AVF Creation vs Surgical AVF Creation

The arteriovenous fistula (AVF) has been around almost as long as chronic dialysis, but there’s a new kid (or two!) on the block. Let’s see if it’s time for us to get over the old methods and move on to the 21st century for vascular access.

Percutaneous AVF Creation

A percutaneous vascular access for hemodialysis (HD) conjures up the vision of a central venous catheter (CVC), and these have been around since the last time the St Louis Hawks made it to the NBA finals. Stanley Shaldon used the Seldinger technique and made a few additional modifications to the catheter design to allow first arteriovenous, and then venovenous femoral cannulation for chronic HD. But that was half a century ago, so what’s new about percutaneous vascular access in 2020? It’s not about CVCs, but about creating the AVF percutaneously. Yes, you read that right – no need to make an incision, suture the skin, and leave an ugly scar to make an AVF. Read on to understand two new techniques, or rather devices to be more accurate, that describe how to make an AVF using percutaneous methods. These percutaneous AVFs, abbreviated as pAVFs, are described in more detail below. 

Copyright: Illus_man / Shutterstock

Broad principles
The two devices that have been described use slightly different approaches to create an AVF, but have a few things in common. Unlike the classical radiocephalic or brachiocephalic/brachiobasilic AVFs which utilize superficial veins, pAVFs are anastomoses, utilizing the radial or ulnar artery and a deep vein of the forearm. Sometimes known as venae comitantes (plural of vena comitans or accompanying vein) because they accompany the radial and ulnar arteries, the radial and ulnar veins communicate with the superficial system via perforating veins. The “comitans” aspect of these veins makes them ideal for a percutaneous approach which does need any surgical dissection. These deep veins are not suitable for cannulation, thus the perforating veins are essential to carry the increased blood flow from the artery into the superficial veins for use. 

Figure by @AriellaStudies; adapted from Wikimedia

WavelinQ
WavelinQ is the first of these new techniques we will discuss. It was previously known as “EverlinQ” (until the technology was bought by Becton-Dickinson and renamed). It relies on the use of two magnetic catheters which align the radial or ulnar artery with the corresponding deep vena comitans. Radiofrequency energy is used to create a channel between the two, and as a consequence the increased blood flow from the deep vein gets channelled into the superficial veins for use via the perforating veins.

The everlinQ endoAVF System. Abbreviation: RF, radiofrequency. Figure 2 from Lok et al, AJKD

The increased blood flow can also flow proximally into the draining basilic vein, which lies deep within the arm and drains into the axillary vein, and would completely thwart superficial vein development. This was realized during the development of the technique, so brachial vein embolization, which further hastens fistula maturation directed at the superficial veins, quickly became a part of the procedure. The deep veins are accessed through the same brachial vein which is eventually embolized. The artery can be accessed from the brachial artery, or at the wrist, though in the United States only the brachial access is approved, given the paucity of data around potential safety and performance at wrist.

Lastly, this procedure is done under fluoroscopy and does require iodinated contrast. Now you might think from a previous #NephMadness region that contrast doesn’t cause acute kidney injury, but we are talking about 75-150 ml contrast in an individual with a GFR less than 15. There’s a non-negligible chance of tipping things into dialysis faster. 

Check out these two videos for a better understanding of this technique: 

Ellipsys
The Ellipsys system requires a single catheter, is done with ultrasound guidance alone – so no radiocontrast – and creates an anastomosis between the proximal radial artery and a deep perforating vein. The vein is first accessed via the median basilic or the median cephalic vein, and the catheter is then advanced into the adjacent proximal radial artery, followed by a radial artery sheath. The Ellipsys catheter, specially designed to allow approximation of the artery and vein, is then advanced through the sheath, and the sheath itself is withdrawn into the vein. The device is then activated which causes tissue fusion through the arterial and venous walls and creates the actual anastomosis.

Empiric Data
Both these techniques/devices have obtained the CE mark and Food and Drug Administration approval, allowing them to be used in the United States and Europe. There are several studies leading up to this, and they are summarized in the table below:

Advantage over surgical AVF
There are several obvious advantages of pAVF over surgical AVF creation. In terms of anesthesia, these can be done with local or regional anesthesia with sedation, and do not need general anesthesia. A patient having had previous radiocephalic AVF does not preclude having another AVF created using endoAVF methods. These are same-day procedures, which can be done in many settings, and do not need formal surgical and/or anesthesia consults in advance, thus shortening the time from decision to AVF creation. There is no incision, there are no sutures, and site healing is much quicker. The vessels are not clamped or dissected, so there is less trauma and potentially fewer vascular complications such as pseudoaneuryms and early stenosis/thrombosis. The short term data we have supports the lower complication rate. These pAVFs also might allow for earlier cannulation, with reported studies suggesting cannulation at 4-6 weeks. Also, they can be created by interventional nephrologists in addition to interventional radiologists or vascular surgeons. 

In conclusion, pAVFs are the present and the future. 

COMMENTARY BY ANIL AGARWAL:
Percutaneous AVF Creation Will Revolutionize Care in Hemodialysis

Surgical AVF Creation

History
On March 9th 1960, Belding ‘Scrib’ Scribner, with the help of Wayne Quinton (a biomedical engineer) and David Dillard (a pediatric cardiac surgeon) created the first arteriovenous shunt in Clyde Shields in Seattle, making chronic HD a reality. The shunt consisted of Teflon tubing surgically inserted into an artery and vein in the arm and exteriorized through the skin and connected by a plastic cannula when not being used for dialysis. However, the Scribner shunt had to be handled very carefully and only lasted for days to weeks. 

Copyright: nimon / Shutterstock

Fast forward to a few years later and to the East Coast: At a Veterans Affairs Hospital in the Bronx, James Cimino was getting increasingly frustrated with the finicky shunts that he was using for chronic dialysis. Legend has it that he recalled using the traumatic AVFs for blood draws in Korean war veterans in the 1950s, when he was working as a phlebotomist. He convinced his surgical colleague Kenneth Appel to deliberately create an AVF in a patient with kidney failure, and the AVF was born. Though the first AVF didn’t work, the second one (which was created in patient “J.S.” on March 9, 1965, exactly 5 years after the first Scribner shunt) did. Thus, the Brescia- Cimino AVF was born, and has served the dialysis community faithfully for the last 55 years. Why mess with something that has withstood the test of time?

Outcome data
One has to admit that right from the beginning, surgically created AVFs have had issues. The first one didn’t work at all, and overall 2 of the first 14 in the first report didn’t work. There was a staphylococcal infection at one site. The failure-to-mature rates are indeed high, 23%, according to this systematic review.

Visual Abstract by @Vernisartan on Al-Jaishi et al

If one looks for high quality data, it gets even worse: ~ 60% of the AVF from the Dialysis Access Consortium (DAC) trial of clopidogrel were not usable at 120 – 150 days after creation. Similarly, in the prospective Hemodialysis Fistula Maturation (HFM) study, unassisted AVF maturation was 50% at 6 weeks. One can argue that the complexity of patients who start HD is dramatically different now than it was in 1965 (median age was only 45 years in the first case series). The radiocephalic site has since expanded to many other sites, with the brachiocephalic and brachiobasilic (often with a basilic vein transposition to allow needling of this deep vein) being the most common options. But surgical ingenuity has allowed the creation of AVFs using the axillary artery, the femoral and popliteal arteries, and even the dorsalis pedis. It is also clear that there is surgical variability that affects AVF outcomes, as seen in the DAC and HFM studies, bringing into focus the importance of surgical experience and expertise. 

New developments 
Apart from new sites, there is not significant ongoing research which shows us a way to improve maturation and durability of the surgical AVF. One of the hindrances in a field like vascular access is the wide variety of definitions used for outcomes. As part of the Kidney Health Initiative, this review establishes and clearly defines the key endpoints for clinical trials in arteriovenous access. We know much more about when AVFs are more likely to fail, with a validated “failure to mature” equation. How do we improve maturation rates? Start with a good surgeon! This recent study reports how surgical volume (i.e. number of AVFs created) has a linear relationship with the likelihood of subsequent AVF maturation.

Visual Abstract by @EricAu on Shahinian et al

Though pharmacological strategies such as antiplatelet agents and fish oil have not been successful, a Scottish clinical trial reported an improvement in patency rates with a brachial plexus block, when compared to local anesthesia. Another trial reported on the efficacy of an implanted biocompatible device (‘VasQ’, from Laminate Medical Technologies Ltd) resulted in a doubling of functional patency at 6 months. One can always keep working and finessing to improve on a technique now 6 decades old.  

(A) The VasQ device, consisting of a brace and a braid. (B) VasQ implant in its final expanded state over the anastomosis and juxta-anastomotic region of a brachiocephalic arteriovenous fistula. Figure 1 from Karydis et al, AJKD

Advantage over percutaneous
While surgical AVFs require careful patient selection as well, the absence of patency of the perforator veins does not hinder surgical AVF creation, making surgical AVF creation possible in a variety of locations. We have solid, robust data on long term outcomes with surgical AVFs, which we don’t have for the endoAVF technique beyond the two-year follow-up from a couple of studies for the pAVF devices. Let’s review the prior table again, but from a different viewpoint.

*arguably the real test of patency

As is readily apparent, these data do not support a slam dunk vote in favor of pAVF, rather support its careful use in properly selected patients only. In fact, as one can see, the actual data from the multicentre prospective trials is less rosy than the smaller initial studies (and the retrospective data report 100% success rate and no complications). In reality, many patients do seem to require secondary procedures, so they avoid their surgeon, which is offset by many visits to the radiology suite. Yes, now the techniques have been refined, and coil embolization, as an example, is planned and performed in the initial procedure itself. The data from the larger multicentre prospective trials seems more robust, so just see the actual patency data from the Novel Endovascular Access Trial (NEAT trial):

Table 3 from Lok et al, AJKD

The pAVFs are the latest shiny new things in a rich tradition of surgical-nephrological collaboration that spans many decades. They do offer another site using the deep forearm veins (that have been used in the past). While these are an evolutionary change, can they be truly called revolutionary? Surgical AVFs remain the tried and trusted vascular access for the majority of chronic kidney disease patients. 

EU Guidelines vs American Guidelines

Despite pleas to decrease the proliferation of guidelines, there is no dearth of new guidelines being released every year. There is a paucity of high quality clinical trials in Nephrology, which has changed only a bit since the first report by Strippoli et al. However, we have not stopped churning out more practice recommendations from the guideline factories. NephMadness is no stranger to the battle of guidelines (see hyponatremia in 2018 and hypertension in 2019). With both the publication of the European (ERBP) access guidelines in 2019 and the American (KDOQI) vascular access guidelines hot off the press, now is an appropriate time to return to this transatlantic battle. Read on as we try to make sense of how the same literature can produce different recommendations after passing through the workgroup prism. 

EU Guidelines

Process and Grades
The EU Guidelines are clinical practice guidelines (CPGs) from the European Renal Association (ERA)’s European Renal Best Practice (ERBP). The workgroup itself comprised 44 participants: 25 nephrologists, 9 surgeons, 3 radiologists, 5 researchers, 2 nurses, and 8 methodologists (categories not mutually exclusive). It included 29 men and 15 women. The guidelines, a 42-page document, begin with a very helpful 3-page summary of the main recommendations. There is an “advice for clinical practice” section after each chapter which translates the “guideline-ese” language into plain English with practical implications. In addition, the actual recommendations and the rationale behind them are always followed by a small section consisting of comparisons with existing guidelines, such as the Canadian Society of Nephrology (CSN), Kidney Health Australia – Caring for Australians with Renal Insufficiency (KHA-CARI), and US KDOQI (the previous version). Lastly, they end with a very helpful “future research needs” section. 

Copyright: koya979 / Shutterstock

What about the evidence behind the guidelines? They use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, as explained in the two tables below. 

Quality of Evidence

The ERBP workgroup ended up with 32 guidelines, which are broken down based on the strength and quality below:

Strong recommendations

There are 5 “We recommend” Grade 1 recommendations with differing quality of evidence, as summarized in the table above. The ERBP workgroup recommends (1C) giving preoperative antibiotic prophylaxis for arteriovenous graft (AVG) insertions, based on 2 small trials (5.1). This is accompanied by a lower (2D) recommendation, extrapolated from the above, suggesting the use of preoperative antibiotics in complex arteriovenous access procedures.

The next strong recommendation (1C) is against giving warfarin in combination with antiplatelet agents, and against clopidogrel in combination with high dose aspirin for the purpose of reducing AVG thrombosis (8.4). We will discuss that in more detail below in the “Pharmacotherapy” section.

The workgroup recommends (1B) that early cannulation AVG can be cannulated….early, as soon as wound healing permits (6.4). But AVFs should not be cannulated (1B) sooner than 2 weeks after their creation (6.2).

There is another strong recommendation (1D) for using only blunt needles for buttonhole cannulations (10.2) which is obvious, given the point of buttonhole cannulations. 

Pharmacotherapy and other Interventions
There are many recommendations in this area. Both workgroups reviewed the same data and came up with interesting differences, as summarized in the table below:

Catheter section
There are no recommendations for catheters. Perhaps it harmonizes with the continental ethos that catheters are evil and should never be used. However, to be fair, these are guidelines explicitly labelled for “arteriovenous access”, hence this is completely acceptable. 

AV Cannulation
There is a short chapter on cannulation with two recommendations (both 2D):  

1. Don’t use the area technique(cannulating the same general area, but not necessarily the same point, session after session) for cannulating AVFs, and  
2. Use the rope-ladder or buttonhole techniques for AVFs, with the choice dependent on local expertise and AVF characteristics. 

This is somewhat puzzling considering that the largest trial comparing the two techniques showed an increase in infections with the buttonhole technique, including abscesses and bacteremia. This trial also did not demonstrate any difference in pain while needling, another area where the neutral results from trials contrasts with the biased outcomes from observational data. Even the longer term data do not support that buttonhole cannulation prolongs AVF patency and survival.

Why promote buttonholes at all then? There is strong patient and nursing preference for buttonhole needling (apparent in self-needling home HD cohorts), such that this preference influenced participation in a recent trial, where only 14 of 50 eligible patients consented, and 3 of the 7 centers couldn’t enroll any patients. Mercifully, the workgroup doesn’t think it is necessary to have ungraded recommendations for every single thing we do. Of course, AVGs should not have buttonhole cannulation. That piece of common sense, presented as “advice for clinical practice”, appropriately does not contribute to the guidelines bloat. 

Choice of Anesthesia
The workgroup suggests (2C) using regional block anesthesia rather than local anesthesia for AVF creation (2.1). Why might they do so? There is an actual randomized controlled trial demonstrating the superiority of regional anesthesia. In this multicentre trial from Glasgow, 126 patients were randomized to brachial plexus block compared to local anesthesia. Using regional block anesthesia improved patency by a whopping 22% at 3 months, and even functional patency for the radiocephalic AVFs by 33%. This is a good spotlight on the few areas in which efficacious interventions have been demonstrated in randomized trials for vascular access. 

Unique aspects
One likeable aspect of these guidelines is their conciseness (42 pages total with a 3 page summary at the start), which is mainly possible because of the number of guideline statements (“only” 32), compared to the behemoth that you can read about below. Rather than have prescriptive statements about every single action, the guidelines are restricted to areas where there are some studies and data to support making a recommendation. Hence, none of the 32 recommendations are based on expert opinions, despite the workgroup being composed of vascular access experts. Apart from the refreshing brevity, useful features include the “advice for clinical practice” (which is very practical) and the comparisons with other workgroup guidelines highlighting the difference of opinion that one can have with the same evidence base. 

American Guidelines

Process and Grades
The American guidelines are the official guidelines from the National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) workgroup, which had 16 members with representation from nephrology, interventional radiology, vascular surgery, and nursing (but no patients or patient advocates). The group was led by Dr. Charmaine Lok from the University of Toronto. In addition, there was also an 8-member evidence review team separate from this workgroup.

Copyright: koya979 / Shutterstock

Similar to the European workgroup, the KDOQI guidelines followed the GRADE framework with some subtle differences, namely a section for ungraded recommendations based on workgroup consensus (AKA expert opinion). As a result of the 170 guideline statements (106 of them being based on expert opinion), the KDOQI guidelines is supersized at 164 pages. 

The quality of evidence assessment was the same (high, moderate, low and very low). For a breakdown of how the guidelines were rated, see the table below:

Strong recommendations
There are 12 strong recommendations in the KDOQI guidelines (as opposed to only 5 from the European guidelines). Some of the strong recommendations include: 

• Use of image guided CVC insertion to improve success (as opposed to blind insertion?).
• Regular physical examinations of the AV fistula by a knowledgeable and experienced health practitioner.
• Physical examinations of an AV graft. Though not a strong recommendation, there is an interesting suggestion that the committee considers it reasonable for trainees to be trained to conduct physical examinations.
• Use of intraluminal tissue plasminogen activator (tPA) to restore function to dysfunctional catheters.
• Use of either tPA or urokinase plus citrate to restore blood flow in an occluded catheter.

Pharmacotherapy
See the table in the European Guidelines section above. 

Catheter section
This is completely different from the European guidelines, which do not even consider CVCs. Some interesting recommendations stand out in this section. The KDOQI guidelines suggest that tunneled CVCs are acceptable for the short or even for the long term in certain situations (eg, poor life expectancy, based on the patients’ ‘life-plan’). Additionally, they are very explicit that the preference for AVF or AVG over CVC is mainly due to the lower risk of infection, with there being insufficient evidence for AVF/AVG being superior at lowering the risk of hospitalization or mortality (for both incident or prevalent patients). That’s an evidence-based step away from the fistula-first religious fervor.

They do suggest that a temporary non-tunneled CVC be kept for a maximum of 2 weeks. They also suggest that there is no maximum time limit for cuffed tunneled CVC when considered permanent, though there is no mention of embedded CVCs and what to do with them. Since we do have a trial in this area, the workgroup suggests that tPA may be prophylactically used once per week (21.6) for maintaining line patency. They also suggest that low-dose aspirin may be used to maintain CVC patency (21.9). 

AV Cannulation
The KDOQI guidelines recommend rope ladder cannulation as the preferred cannulation and consider it reasonable to limit buttonhole only to special circumstances given the risk of infections (11.2 and 11.3). The experts advise avoiding buttonholes with AVGs. The discussion reviews the trials and observational studies, which report no difference in AVF survival, no difference in quality of life, and a higher risk of access infections and bacteremia with the buttonhole technique. The evidence for harm with buttonhole needling was appropriately weighted to be strong for bacteremia, with a relative risk of RR=19 (95% CI: 8, 46) and a risk difference of 0.13 (95% CI: 0.05, 0.21) in the Canadian trial.   

Choice of Anesthesia
Unlike the European guidelines, the KDOQI guidelines suggest that the choice of anesthesia for AVF creation should be based on the operator’s discretion and best clinical judgment (8.2). They also state that the current evidence shows no difference between the regional block and local anesthesia in terms of usability, patency, interventions, or patient experience. This is different from the European European guidelines. The workgroup found 6 trials and 3 observational studies, and performed a pooled analysis of 3/6 trials (not including the Aitken et al trial), which did not show a benefit of regional block. They discussed the Aitken trial separately (which was used to justify regional block by the European guidelines); however, given the safety issues with regional anesthesia, this is left to the operator’s discretion. 

Unique aspects
The KDOQI guidelines encompass the entire patient experience (eg, the ESKD LIFE-Plan below) from the predialysis scenario for access planning to detailed considerations of CVCs, AVFs, and AVGs.

• Should there be a multidisciplinary team to educate/coordinate/manage all aspects of dialysis access? (yes, 6.10, expert opinion)
• Should a physical examination focused on vascular anatomy be part of initial assessment for vascular access? (yes, 7.1, conditional recommendation)
• What kind of suture should you use for the AVF creation? (leave it to the surgeon’s discretion, 8.4, expert opinion)
• What side of the bed should the patient get up on on the day of surgery? (right, 5.7, expert opinion).

Just kidding on that last one, but there is an exhaustive set of advice to cover almost any conceivable questions one might have. 

ESKD Life-Plan: Patient-Physician Shared Documentation. Supplement 2 from Lok et al, AJKD © National Kidney Foundation.

– Executive Team Member for this region: Anna Burgner, AJKD Social Media Advisory Board. Follow her @anna_burgner.

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