Renal Interventions 4 - US

July 2022 Issue 04 www.renalinterventions.net

In this issue:

UK Kidney Week: Home dialysis takes centre stage page 8

Late-breaking clinical trials reinforce importance of early detection and treatment in CKD THREE LATE-BREAKING CLINICAL trials presented at the 59th European Renal Association (ERA) congress (19–22 May, Paris, France) have placed increased focus on the need to quickly detect and treat chronic kidney disease (CKD).

Annette Bruchfeld (Karolinska Institute, Solna, Sweden), who is chair of the Scientific Committee and facilitated a press briefing on these new data, said: “CKD is a progressive condition that impacts both life expectancy and quality of life. The results of these late-breaking clinical trials highlight potential new strategies for early detection and treatment of CKD, and its complications, heralding new hope as we work towards ERA’s goal to improve kidney care for every patient.”

The first of these presentations—the THOMAS study—detailed a prospective, randomised trial in which Ronald Gansevoort (University of Groningen, Groningen, The Netherlands) and colleagues evaluated two different homebased albuminuria screening strategies, concluding that home-based screening in the general population has a high participation rate, identifies individuals with unknown CKD and cardiovascular disease (CVD) risk factors, and is cost-effective compared to usual care (no screening).

Further late-breaking research presented at ERA 2022 saw Franz Schaefer (Heidelberg University Hospital, Heidelberg, Germany) and colleagues assess the usefulness of urinary Dickkopf-3 (uDKK3) in determining the short-term risk of CKD progression in children. They concluded that uDKK3 is associated with a greater short-term risk of declining kidney function, potentially allowing a personalised pharmacological approach to kidney function preservation.

Finally, data from the TIPS3 trial were delivered on behalf of Johannes Mann (University of Erlangen-Nuremberg, Erlangen, Germany) and an international team from Canada and India. In an effort to assess the effects of aspirin in preventing CVD among CKD patients, they analysed more than 5,700 participants and found that cardiovascular risks may be substantially alleviated, either with aspirin alone, or in combination with a polypill.

Profile: Aisha Shaikh

page 12

Ziv Haskal on recent DCB data

“Age is just a number” Frailty and vascular access

page 17

page 19

Physicians hear global patient perspectives about life on dialysis From insights on living with different treatment modalities, to problems created by poor physician-patient communication and long-term psychological challenges, kidney care physicians heard a range of perspectives from dialysis patients during two recent conferences—the Vascular Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA) and UK Kidney Week (UKKW; 7–9 June, Birmingham, UK).

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“The focus is often on how your dialysis is going, but not how well you are living,” Hill added. He also said some form of mental therapy may have helped him overcome issues with self-confidence, and a loss of identity, when he started dialysis. These difficulties, according to Hill, are even harder to cope with alongside the fear of dying from kidney disease.

This point was stressed by Ramos-Multani too, who told the audience: “When you say ‘end-stage kidney disease’ to a patient, to them, that means they are dying. That is the beginning of their depression.”

Another message emphasised by patients throughout VASA was ‘no one told me’, with Ramos-Multani saying that a lack of vital information creates even more uncertainty for the patient. “People are going through all sorts of emotions, from fear to denial, and I think trying to overlay information on that emotional fog creates poor communication,” one physician averred. “The message I am hearing is that our community needs to do much better when it comes to communicating and reinforcing these things—because they are obvious to us, but not to the patient.”

Effective communication A common theme at VASA was the need for improved physician-patient communication.

Dialysis patients Fred Hill and Lissette RamosMultani both highlighted this when detailing their own experiences—with Hill calling for “true education” on how each modality will impact a patient’s life. He noted that, beyond simple explanations of how fistulas and catheters work, “it needs to be more about how we live our lives” on dialysis.

Dialysis burnout The long-term psychological toll these treatments can take featured prominently at UKKW, with nocturnal HD patient Nikki Fretwell drawing on the 30-plus years she has spent on dialysis.

Fretwell detailed her experience of living in denial, to some extent, and refusing to let dialysis define her for many years before succumbing to “total burnout” and seeing a renal psychologist. “We talk about tiredness, exhaustion and fatigue,” she said, “but, for me, these words are not powerful enough to describe it.” Fretwell also alluded to putting off everyday tasks until tomorrow, but feeling like “tomorrow never comes” due to a constant lack of energy.

Struggles relating to self-worth and independence, as well as a desire to live life to the full in spite of dialysis, were among other overarching messages here. “I was so determined to be normal that I ignored all my symptoms, and never told anyone how I felt or how hard life actually was,” Fretwell continued, but went on to add that, more recently, she has learned to accept help from others and acknowledge her limits.

“Your life is the priority, and dialysis gives you that life,” she stated, addressing fellow patients.

At VASA, Hill concluded with a similarly positive outlook: “Dialysis is the battery that means you can live—so go and live! And, understand that it is a second chance at life, and a part of your life, but it is not your whole life.”

ne such perspective was offered by Lorin Jackson, who discussed her experiences on peritoneal dialysis (PD), and both home and in-centre haemodialysis (HD) at VASA 2022.

“For me, PD is the best-case scenario,” she said. “It gives me the most flexibility and freedom, and is more gentle, whereas HD is intense and can make you very tired.”

She also noted that PD can be done nocturnally, allowing her to wake up, disconnect and go about her day after dialysing overnight, while she found HD more limiting, requiring greater time and effort. “I would argue that, sometimes, it felt like a full-time job, and I really did feel like I was my own nurse,” Jackson said, also relaying difficulties she experienced on HD, including an access graft occlusion, learning how to cannulate—which was “awful”—and fainting.

“It was always really scary if something went wrong with HD,” she added. “There was a lot of blood, and it was overwhelming. But PD is not like that. It is much more controlled and contained, and it feels safer and more manageable for me.” Jackson relayed that, with some adjustments, she is still able to travel for work, volunteer and focus on her religion with PD—concluding: “You just have to make it work for you.”

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“The focus is often on how your dialysis is going, but not how well you are living.”

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Patient Perspectives

Fistula, graft or catheter? First and foremost, dialysis patients want an access that works “Catheters are not nearly as bad as we make them out to be.” This was one of the salient messages delivered by Theodore Saad (Nephrology Associates, Newark, USA) at the 2022 Vascular Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA). In a presentation based primarily around patients’ experiences on dialysis, he also noted that much of the data suggesting high infection rates and poor outcomes with access catheters are uncontrolled and outdated—and there are select patients for whom a long-term catheter turns out to be their best option.

Renal Interventions later caught up with Saad to expand on some of these themes.

“N

o matter how you slice it, dialysis is something of a burden to most, if not all, patients,” Saad says. “And, patients deal with that burden very differently depending on their health status, their personal circumstances, their family support, their living situation etc. We [physicians] sometimes forget or lose sight of how much of a burden it is because we see it every day but, from the patients’ side of things, it can be daunting, it is a burden, and it can be consuming.”

“From a patient’s perspective, when it comes to their vascular access, they just want it to work,” he continues. “They want it to be painless, reliable and effective, and they do not want to have to worry or think about it. They just want it to be there and for it to work.”

Saad also suggests that being able to de-access, achieve haemostasis and go home quickly with no complications is a patient priority. “Anything that works against that is a negative for them,” he says. “Dialysis is tough enough without struggling to get into [and out of ] the access.”

“Some patients are far more tolerant and accepting of what needs to be done to maintain their access than others,” adds Saad, who sees a wide spectrum of attitudes within his own practice, as some patients will get “very upset, or even hostile” regarding reinterventions, despite only going in for revisions roughly once per year.

Conversely, others require multiple yearly revi-

sions to maintain a very delicate fistula but are fully aware it likely represents “the best access they are ever going to have”, and as such they and their families are “absolutely delighted” just to have it working.

Fistula, graft or catheter?

At Saad’s centre in Delaware, the split between the major vascular access options for dialysis is fairly consistent with other high-quality US practices around the country. “We start most of our patients [60–80%] with catheters—more than we would like,” he says. “We are tracking and monitoring our patients to try to improve on that and achieve the optimal permanent starting access but, still, the majority start with catheters.” Close to 20% of prevalent patients remain on long-term catheters, he states, while 60–65% receive fistulas and the rest (roughly 20%) receive grafts. “That is a pretty reasonable mix, I think, in 2022,” Saad adds.

“To be repeatedly intervening on a fistula and seeing things get worse rather than making forward progress is, I think, the ultimate futility.”

Theodore Saad

“If I go back over the past 30 years, I have seen access patterns go from largely fistulas and few catheters, to largely grafts and few fistulas, to lots of catheters and lots of grafts, to now— where we have a high proportion of fistulas,” Saad continues. He also notes there is some evidence that implementing ‘fistula-first’ guidance led to increased catheter rates in the past, while COVID-19 has negatively impacted efforts to bring catheter rates down by restricting or delaying access to elective surgical procedures.

Saad then reiterates that, rather than having an overwhelming preference for any of these individual access options, “the patients want something that works—whether that is a fistula, a graft or a catheter”. If a patient has had negative experiences on one or two of the other distinct access options, but is currently doing well on another, they are far more likely to favour continuing with whatever has served them best, Saad asserts. This could be seen to reflect the shift away from ‘fistula-first’ towards ‘the right access’ in the 2019 Kidney Disease Outcomes Quality Initiative (KDOQI) guideline update.

Forward progress According to Saad, the worst access option for patients and clinicians alike is a “bad” fistula. A fistula that cannot be easily or reliably cannulated, causes the patient a lot of pain, requires multiple interventions and, ultimately, does not enable adequate dialysis is “miserable” for the patient, the dialysis team, and the nephrologist, he adds. This is why patients who have had poor experiences with a fistula before going on to do very well with a catheter, for example, tend to favour sticking with the latter. “That is their reality and their perspective—I can give them all the data I want, but if they have a catheter that is working perfectly and I tell them I want to try another fistula, that is a hard sell,” Saad says.

“Patients will fail to accept that illogic; they have limited tolerance for failure and for futility.”

In terms of striking a balance between what the data would dictate and what the patient wants based on their experiences, Saad believes ‘forward progress’ is key. “That goes a long way to persuading a patient to stick with a programme and see the light at the end of the tunnel,” he continues, noting that multiple successive fistula interventions can be justified as worthwhile—again, for both patient and physician—provided each procedure is improving outcomes and increasing the likelihood of long-term success. “But, to be repeatedly intervening on a fistula and seeing things get worse rather than making that forward progress is, I think, the ultimate futility,” Saad asserts.

Based upon his experiences as a nephrologist and feedback from his own dialysis patients, Saad concludes that the optimal treatment modality cannot be selected, and dialysis access decisions more generally cannot be made, using a ‘one-size-fits-all’ approach. “It is essential to listen to patients; understand their goals and priorities; appreciate the impact of dialysis on their lives; and, ultimately, support their reasoned, informed choices,” he adds.

Chairman of the Editorial Board: Nicholas Inston | Editorial board: Ziv Haskal, Stephen Hohmann, Robert Jones Publisher: Roger Greenhalgh | Content director: Urmila Kerslake | Editor: Jamie Bell jamie@bibamedical.com Design: Terry Hawes, Wes Mitchell | Editorial contribution: Jocelyn Hudson Advertising (EU): Shilpa Suthar shilpa@bibamedical.com | Advertising (US): Nicole Schmitz nicole@bibamedical.com Subscriptions: subscriptions@bibamedical.com | News or advertising queries: Tel: +44 (0)20 7736 8788 Published by: BIBA Publishing, which is a subsidiary of BIBA Medical Ltd | BIBA Medical, Europe, 526 Fulham Road, Fulham, London, SW6 5NR, United Kingdom Tel: +44 (0) 20 7736 8788 | BIBA Medical, North America, 155 North Wacker Drive, Suite 4250, Chicago, IL 60606, United States Tel: +1 708-770-7323 Printed by: Micropress Printers Ltd. Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the United Kingdom address. © BIBA Medical Ltd, 2022. All rights reserved.

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Renal Interventions July 2022 – Issue 4

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Patient Perspectives

Setting clear expectations early on is an important step in the dialysis access journey One of the outstanding themes explored at this year’s Vascular Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA) was patient perspectives on receiving dialysis treatments. In accordance with this, Stephen Hohmann (Texas Vascular Associates, Dallas, USA) recently sat down with Renal Interventions to discuss a number of key considerations along the dialysis journey, from taking on board a patient’s goals and personal preferences, to managing their expectations.

Hohmann believes that, alongside these factors, educating the patient from the outset and maintaining an ongoing dialogue is pivotal to successful access strategy planning. Here, he also outlines the uptake of each of the major access types in his practice and discusses the everincreasing relevance of peritoneal dialysis (PD) in this space.

Could you outline some of the overriding themes, in terms of patient feedback, that you observe in your practice?

No one wants to be on dialysis, obviously, and when patients first come to see you—particularly if they have not had any previous experience with it—it is really overwhelming. They are thinking about how their life is going to change, and oftentimes as you are talking to them about potential options it can be difficult for them to process things. I think acknowledging that at first is always very helpful to the patient.

My main theme when talking to patients is setting expectations; making sure they understand that dialysis access is not like any other surgery we do. With most surgeries, people expect to see the surgeon or interventionist one time and then be done with them—but this is rarely the case in dialysis. So, it is about conveying that you are not just doing a procedure, but you are actually starting a relationship and a journey with them to maintain their access until they do not need it anymore.

The most common piece of feedback I get is that they initially thought access surgery would be a one-time thing, and that has really shaped the way I speak to patients and their families.

Setting that expectation early on is key.

It is overwhelming for most patients when they hear “you need to start on dialysis”— it is akin to finding out you have cancer.

After hearing those words, it is hard to process anything else, and I think taking some time to reiterate similar themes, and giving a general overview of what to expect initially rather than getting into too much specific detail, is important.

Why are the early stages in a dialysis patient’s journey so important?

The initial discussion is a really key moment in the process, because patients may get it into their mind that this is just a single stop and they will never need to get anything else done to their access.

And then, in the future, once they require an intervention or encounter problems, there is a huge sense of let-down and failure. Repeated complications and reinterventions can also lead to ‘access fatigue’.

I think that, early on, we need to try to July 2022 – Issue 4

understand certain things: What are the patient’s goals? What are they most afraid of when it comes to vascular access, and dialysis more generally?

From there, we can help them make decisions. I always say it is the patient’s choice, which it is, but we also have a responsibility to guide them and give them information to support that choice.

And the other thing I tell patients is that we can always switch; if you choose PD and it turns out not to be right for you, we can try haemodialysis, or vice versa. It is not a finite decision—we can still modify it and, as such, they remain in control of their health. Most of the time, patients are relieved to hear that the choice they make is not final.

What is the split between the major access types—fistulas, grafts and catheters—at your centre?

I would say that, generally, in Dallas, we have more grafts than in most places— possibly because other patient populations have veins that are better suited to fistulas. The proportion of catheters varies from centre to centre, and probably ranges from 30% to 5–10% in some places. Fistulas fall in the 40–50% range, while grafts make up the remainder.

I think the best thing that has happened for us recently is the latest Kidney Disease Outcomes Quality Initiative (KDOQI) guideline update, which stressed ‘the right access, for the right patient, at the right time’. And I use that all the time with the patient, and I explain that there are three access types and each has its advantages and disadvantages. ‘Anything other than a fistula is a failure’ or ‘not having a catheter in the chest is a success’; it is really about changing that narrative, and kudos to the KDOQI guideline writers for giving us that freedom.

Another thing I have seen recently is a definite uptrend in PD. There is a clear

Stephen Hohmann

increase in the number of patients wanting to pursue that—particularly during and post-COVID. A lot of people are very anxious to not have to go in-centre and be around other patients, and PD gives them the freedom to avoid those situations by dialysing at home. The effect of the pandemic as well as governmental influences has driven more people towards home therapies, which is good, because we always say that “you dialyse to live, you do not live to dialyse”. Yes, it is still a clear interruption to their life, but to a lesser extent than having to go to the dialysis centre three times a week.

In light of recent shifts away from ‘fistula first’, what are your thoughts on grafts and catheters as more longterm options?

A graft can be a good option for a long time in the right patient population—like I said, I think it is really about resetting our focus and also trying to get our patients accesses before they need them. In the USA, 80% of people initiate dialysis with a catheter and our focus should be on driving that number down. If that means using more grafts, then fine—grafts can be very good and they can work for a long time. I think the idea that it is a ‘lesser than’ access is the wrong frame of mind to be in, as they do carry plenty of advantages.

I think catheters have a role to play too, and I think this is where the discussion comes back to KDOQI and the importance of assessing the individual patient.

Life expectancy, for example, is one of the more difficult elements for us to predict with any real certainty, but if somebody has an end-stage malignancy and their goal is to dialyse for a specific length of time, catheters should be considered.

They are also a good option in people with severe peripheral vascular disease, or those who have had multiple abdominal surgeries and cannot undergo PD.

“The most common piece of feedback I get is that they initially thought access surgery would be a one-time thing, and that has really shaped the way I speak to patients and their families.”

However, the role of catheters should be limited and we should be careful regarding patient selection because there is clear evidence that, statistically, they encounter more problems than other accesses. I would love to see that 80% rate of patients starting with a catheter flipped on its head, and brought down to 20% or less.

We really need to take a close look at that population and get those numbers as low as possible.

How do you attempt to balance your own knowledge and expertise with patient preferences?

I think that is where patient education is vital. It is also about asking the patient what they want rather than telling them what we are going to do—and, sometimes, they do not know, which is okay too.

Either way, it is about taking their feelings on board, assessing all the options, and going back to them with an optimal access strategy based on what they have told you.

Being open with the patient is key too.

Some people may want to try PD despite having had previous abdominal surgeries, and it may be a case of doing a diagnostic laparoscopy to see if it is possible.

Even if it turns out PD will not be possible, patients do tend to be appreciative of these attempts to explore their preferred option. The same goes for patients who want a fistula—we can try, but if it is unsuccessful, they may need a graft instead. I would say that, once you offer that level of education regarding each option and lay out the reasoning, most patients are more receptive.

I also feel that one thing we in the surgical world can probably improve on is our understanding of cosmesis. For the patient, not only are they going to be on dialysis, but they are also going to have a visible access in their arm that tells the world there is something wrong with them. That is a big concern for patients and it is something we need to be empathetic about. I always say ‘function first’ because, if it does not work, nothing else matters, but the form is also relevant, and I think we need to appreciate that the way patients look is important to them and should therefore play a role too.

Interventional Nephrology

Interventional nephrology supercharged by soaring interest at 2022 vascular access and kidney care conferences At the recent EndoVascular Access meeting (EVA; 24–25 June, Patras, Greece), and UK Kidney Week (UKKW; 7–9 June, Birmingham, UK), renal healthcare professionals had the opportunity to experience bespoke modules and didactic learning on kidney biopsy, ultrasound use for kidney assessment, cutting-edge vascular access updates and peritoneal dialysis (PD). Experts suggest this amplified, well-tailored exposure will help enhance interest in interventional nephrology and support the development of much-needed procedural skills.

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ürkan Sengölge (Medical University of Vienna, Vienna, Austria) set the scene for the need for targeted interventional nephrology training when he commented in his EVA presentation that there were studies showing that short-term, focused training can put nephrology fellows on par with interventional nephrologists in terms of technical skills.

Nephrology Partnership for Advancing Technology in Healthcare (N-PATH), which is described as an innovative European training course in interventional nephrology funded by the European Commission in the framework of the Erasmus+ programme coordinated by the University of Bari (Bari, Italy) in collaboration with the European Renal Association (ERA), the Vascular Access Society, important international academic centres and two companies specialised in medical training, aims to do just that. It seeks to fortify nephrology training with a view to tackling the increase in kidney diseases across the continent. N-PATH will train 40 young European nephrologists from eight different countries, giving them the opportunity to interact and benefit from this two-year educational path.

Twelve nephrology residents from across Europe were selected to attend the EVA meeting. Maurizio Gallieni (University of Milan, Milan, Italy) told Nicholas Inston (Queen Elizabeth Hospital, Birmingham, UK) when discussing the project.

“N-PATH is dedicated to developing a selected number of nephrology fellows’ interventional nephrology abilities. The concept of N-PATH is blending traditional learning and online learning, and it emphasises learning with hands-on training. So, all the fellows will travel to the eight institutions that are part of the project. In addition to the training, these participants will also have the possibility to create bonds among the group and develop interventional nephrology in the future,” said Gallieni.

“Many of the next generation of nephrologists evidently seek to acquire interventional skills,” Inston added. “This will facilitate a wider role in the assessment, surveillance, maintenance and, in some cases, creation and salvage of dialysis access. This enthusiasm is very encouraging.”

N-PATH is made up of four modules: REMAP (kidney biopsy, renal expert in molecular pathology), REVAC (renal expert in vascular access), REMUS (renal expert in medical ultrasound), and REPED (renal expert in peritoneal dialysis), Gallieni further detailed.

“The students will have access not only to a dedicated digital platform but, also, they will have the opportunity to put into practice what

“This is something that I will take back to the USA. I love this programme and finding out more about it.”

they have learned during the training course through varied hands-on training across Europe, creating a 360-degree educational experience,” a press release outlining the project says.

When asked by American Society of Diagnostic and Interventional Nephrology (ASDIN) past-president Monnie Wasse (director, Interventional Nephrology, Rush University Medical Center, Chicago, USA), Louis Firket (Centre Hospitalier Universitaire de Liège, Liege, Belgium), Raquel Barba Teba (Hospital Universitario Infanta Leonor, Madrid, Spain) and Georgia Georgopoulou (University Hospital of

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Patras, Patras, Greece) all praised a “great initiative” providing a valuable opportunity to learn best interventional nephrology practices from the participating universities, and develop their skills and take them back to their home countries. “This is something that I will take back to the USA. I love this programme and finding out more about it. Thank you so much for talking with me today,” said Wasse.

Asked by Inston about what these fellows may gain specifically from the EVA meeting, Gallieni said it had allowed N-PATH fellows to “get together again” as well as “provide exposure to a cutting-edge meeting on vascular access, facilitating interaction with other specialists—in particular surgeons and interventional radiologists, which is something they do not currently get in the curriculum of the N-PATH project”.

Hands-on training for renal healthcare professionals also took place at the first UKKW interventional nephrology workshop, with stations on PD; central venous catheter placement using a state-of-the-art simulator; a ‘home-made’ chicken model to practise renal biopsy; and an ultrasound model allowing the display of kidney pathology and physiology (all pictured below).

In addition to supporting the training of kidney specialists, the UK Kidney Association (UKKA)—as an organisation for all healthcare professionals involved in kidney disease care—is focused on ensuring that clinicians other than doctors are also supported regarding enhanced training in interventional nephrology. That is according to UKKA president Paul Cockwell (Queen Elizabeth Hospital, Birmingham, UK), who said: “Our aim is for comprehensive interventional nephrology as a core component of renal services. In the UK, this is being increasingly delivered by renal doctors and by other healthcare professionals, including specialist renal nurses. Understanding how the workforce and infrastructure is best configured to address the needs of patients with kidney disease is crucial.”

Peritoneal dialysis

Central venous catheters

Ultrasound

Renal biopsy

Monnie Wasse

“The concept of N-PATH is blending traditional learning and online learning and it emphasises learning with handson training.”

Maurizio Gallieni Issue 4 – July 2022

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EVA

EVA meeting harnesses global, multidisciplinary experts and analysis to guide the way in vascular access Lively discussion on unmet needs and building on quiet developments in vascular access from leading surgeons, interventional radiologists, nephrologists and interventional nephrologists formed the backbone of the recent EndoVascular Access (EVA; 24–25 June, Patras, Greece) meeting’s programme.

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ractice patterns and data from around the world that most of the focus to date in this area has been on were brought to delegates via special sessions from vessel mapping and size criteria, and the presence of the USA, with CiDA@EVA (Controversies in Dialy- the perforator. “More understanding of whether predisis Access); the Middle East with PAIRS@EVA (Pan Arab alysis patients or those already on dialysis will benefit Interventional Radiology Society); and the Asia Pacific the most from endoAVF is another good example, as is with DASy@EVA (Dialysis Access Synergy). Important recognising recent studies in surgical fistulas that have developments in transplantation—such as organ utili- demonstrated major differences in fistula use and success sation strategies and xenotransplantation—and home between ethnic groups,” he pointed out. “We do not have haemodialysis (HHD), both of which often sit outside the these data for endoAVF.” traditional realm of vascular access but raise important Inconsistencies in endpoint definitions are abundant in questions on how best to manage patients with end-stage the literature, Jones also warned. “I think there does need kidney disease (ESKD), were also in focus. to be some consistency with definitions moving forward, “There are a whole host of new procedures on the hori- so we can make meaningful comparisons between all zon, such as the percutaneous creation of arterithese different studies.” He called for more focus ovenous fistulas [AVFs], including those that are on cannulation as “that is what is important to the precision-guided. The EVA programme aimed to patient”. “Ultimately, they are the end user and, go beyond traditional silos in terms of specialities whilst we talk about the scientific side of things, and topics to examine [them] from an evidencethere needs to be more focus, understanding and based perspective, as they affect our understandeducation around cannulation,” he added. ing and management of vascular access patients. Robert Jones This was truly a broad-spectrum vascular access The war on access dysfunction using drugs meeting with a global faculty,” EVA course direcWhile the safety and efficacy of drug-coated tors Dimitrios Karnabaditis, Konstantinos Katsaballoons (DCBs) in dialysis access is increasingly nos and Panagiotis Kitrou (all University of Patras, being backed by mid-to-long-term evidence, Patras, Greece), told Renal Interventions.

Haskal recently warned against “optimistic overKey trial updates were presented, including on exuberance” here in an interview with Renal the Ellipsys vascular access system (Medtronic), Scott Trerotola Interventions (see page 17). At EVA, he spoke on the the AVENEW study (BD), first clinical experiences benefits of getting data from industry trials with with the Wrapsody endoprosthesis (Merit), and tight populations and controlled situations, but the EVA DROP study. The latest research—for asked Scott Trerotola (University of Pennsylvania, example, on how ‘omics’-based analysis could Philadelphia, USA): “How do you compare these optimise central venous stenosis treatment—and populations one to the other when they all live new technologies, such as a remote monitorlike these beautiful, independent Greek islands? ing system providing continuous haemodialysis Michael Aragon Can you take the group from one and case control access data (Alio), were also discussed. into another, and then draw conclusions?”

Trerotola initially qualified by saying a biostatistiCatheter arms race and modulating mega fistulas cian would likely answer with an “absolute no”, adding: Ziv Haskal (University of Virginia, Charlottesville, USA) “When you have a whole bunch of studies that have been alluded to the 20-year arms race of catheters and empha- done exactly the same way, and have the exact same sis on “larger and larger sizes, and coatings”, which have signal—for example, the control groups in all of these DCB never been tested in head-to-head comparisons to show studies remarkably show the same outcomes in terms improvements. “And, yet, we are still focusing on those,” of primary patency […] when you start seeing the same he said, calling for a shake-up in thinking. Turning tack to signal repeatedly, maybe we are really onto something.” balloon maturation, he pointed out that interventionists Elsewhere, Katsanos provided a whirlwind tour of would do well to enhance their understanding of what increasing interest in the limus family of drugs, describing it takes to get a fistula to mature—whether it is created them as a “large group of rapamycin analogues that are by surgical or percutaneous means—and not simply use cytostatic, rather than cytotoxic, which paclitaxel is”. He balloon angioplasty as a go-to procedure. noted that limus drugs offer a potential alternative to pacl“I wanted to highlight that, outside of our narrow itaxel due to their wider therapeutic margin and mode tunnel vision of the pipe, which we have to either create, maintain or make larger, there are important examples of unmet needs, such as the long-term cardiovascular consequences of high-flow fistulas,” Haskal added. “We know annual cardiovascular mortality is so very great in these patients. And, we need technology to be able to modulate those mega fistulas. On the other side is the systemic atherosclerosis; the extraordinary peripheral arterial disease and critical limb ischaemia that we must provide care of. We need defined approaches that are unique to this population and to keep this in everyone’s minds.”

Untapped research areas for endoAVF Robert Jones (Queen Elizabeth Hospital, Birmingham, UK), president of the Vascular Access Society of Britain and Ireland (VASBI), asserted that, while all eyes are on percutaneously created fistulas, there are still significant untapped areas for research and education in endoAVF. “Patient selection is a great example,” he said, noting July 2022 – Issue 4

EVA course directors (left to right): Dimitrios Karnabatidis, Panagiotis Kitrou and Konstantinos Katsanos

of action. “There is a large family of ‘rapalogs’ already widely effective and used in coronary artery disease. Two randomised controlled trials of sirolimus-coated balloons in the treatment of AVF stenoses are currently underway with two different platforms using different doses of sirolimus, and their results are anticipated,” he concluded.

Robust as opposed to real-world angioplasty Comparisons across studies that used different device types clearly pose an additional challenge and might even be entirely unscientific, said Trerotola. “Still, one of the things that has perplexed me is, if you look at the control arm of the AVENEW study, the results of plain-balloon angioplasty are really quite poor. They are much lower in terms of patency than all of the control arms in these DCB trials. And why is that? Well, if you ask principal investigator Bart Dolmatch [Palo Alto Medical Foundation, Mountain View, USA], he will tell you it is because they did not perform the same kind of angioplasty.” At EVA, Trerotola noted that some have deemed this “real-world” angioplasty, to which he countered: “Not in my world.”

Trerotola told Renal Interventions: “Again, you may not be able to compare these different studies, but if you can get good angioplasty, why not do it?” The theme of “good” high-pressure balloon angioplasty was further examined in light of the PAVE trial, which did not show a significant benefit with DCB use as high-pressure balloon angioplasty results were unexpectedly robust. PAVE principal investigator Narayan Karunanithy (Guy’s and St Thomas’ NHS Foundation Trust, London, UK) noted that “good” high-pressure balloon angioplasty for failing access circuits could make all the difference. “One of the strengths of PAVE is that it had independent adjudication of results by ultrasound. The idea that high-pressure balloon angioplasty for dysfunctional dialysis access circuits is a good first approach, followed by DCB, and covered stents can be reserved for bailout situations in cases where evidence is missing, might be worth exploring,” mused Kitrou.

Ultrasound poised to be ultra-important In his presentations, Stavros Spiliopoulos (National and Kapodistrian University of Athens, Athens, Greece)—notably on the VOLA pilot study—stated that ultrasound is an indispensable tool for endovascular procedures in dysfunctional vascular access. “Ultrasound provides anatomical, haemodynamic, quantitative and qualitative data, essential for accurate procedural design and intraprocedural decision-making,” he said. “Specifically, intraprocedural volume-flow measurements have recently been used as a functional endpoint that could improve angioplasty outcomes in AVF treatment and lesion-type characterisation using ultrasound enables individualised treatment options.”

Home is where the dialysis should be Michael Aragon, nephrologist and chief medical officer of Outset Medical, outlined existing benefits and barriers to HHD. “If we really want to look at how we are going to shape the future of dialysis, we need to think about the clinical outcomes that physicians are interested in, but also how to improve the patient experience [which is poor with in-centre dialysis],” he said. HHD is associated with improved quality of life, reductions in dialysis recovery time and lower drug burden, he detailed, while the majority of comparative analyses show that HHD tends to demonstrate better mortality outcomes too. According to Aragon, while surveyed nephrologists and dialysis nurses would strongly opt for HHD for themselves—particularly if transplant is not an option—barriers and biases need to be addressed before they are convinced it is the best option for patients.

Aragon said physicians historically lack confidence that patients can administer their own therapy, which leads to their patients adopting similar biases. “Those of us experienced with HHD know that is not necessarily true,” he added. “We have not [previously] had technologies designed specifically for patients in the home environment, historically making it very complex and difficult.

Technology has often facilitated solutions to some of the greatest challenges in healthcare. So, when we look ahead, to me, it is HHD. It is patients caring for themselves with simplified technology, reducing the burden on the healthcare system. It is the ability for physicians to finally prescribe dialysis with flexibility; to look at a patient and ask: How do I fit dialysis into your life as opposed to trying to fit your life into my dialysis schedule?”

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8

UK Kidney Week

Dialysis / UK Kidney Week

Funder engagement and patient support essential to home dialysis growth Funder-provider engagement and patient education are vital in growing home dialysis uptake across an entire region or country. Financial incentives or performance targets are among key options for achieving the former— while the assessment of all end-stage kidney disease (ESKD) patients for home dialysis eligibility, followed by adequate encouragement and continued support, is also critical. These messages were conveyed by Peter Blake (Western University, London, Canada) during his presentation of ‘the Ontario experience’ at UK Kidney Week (UKKW 2022; 7–9 June, Birmingham, UK).

B

lake began by noting that, as much as many global healthcare systems would like to grow their usage of home dialysis— and, in particular, peritoneal dialysis (PD)—for cost- and patient care-related reasons, in-centre haemodialysis (ICHD) is still the default modality “almost everywhere”. He added that this is mostly driven by simplicity and corporatisation.

One of the key points that Blake pressed home throughout his UKKW talk was that growing home dialysis in a region or country, in general, is not possible without a systematic initiative.

He also said it is important to assess all ESKD patients as possible home dialysis candidates from the outset. Sufficient funding is “inevitably required” too, Blake added.

In an effort to boost home dialysis rates, which had waned since the turn of the century—despite PD and home haemodialysis (HHD) being very popular in the 1980s and 1990s—the Ontario Renal Network (ORN) launched a multifaceted initiative in 2012. According to Blake, this was based around five enablers and 14 interventions, including a new, dedicated funding formula; a single, provincial data reporting system; and increased involvement of the ORN to build a ‘true network’ centred around a culture of accountability. Blake noted that this process “takes time—but was achieved”, in part via the introduction of new roles and regular meetings.

The speaker also highlighted the need to maintain “true modality choice”, adding that home modalities are not mandated and the majority of patients still receive ICHD. Patient education, support and encouragement, as well as expert advice—coupled with clinicians being advised to consider home dialysis as the first option “if at all possible”—helped provide patients with a full range of options, Blake said. Initiatives from multidisciplinary pre-dialysis clinics and regular, comparative ‘benchmarking’ between programmes, to greater PD usage in long-term care homes and even subsidising water bills for patients on HHD, were deployed too.

Blake reported that all of these measures fed into a home dialysis target of 27% across Ontario. Individual programmes and centres were, however, given realistic goals based on their own starting rates, with active performance management including discussions, site visits, reviews and, previously, small funding penalties, being used in programmes falling short of their targets.

Delivering 10-year data on the impact of this initiative, Blake said Ontario’s home dialysis rate

July 2022 – Issue 4

began at around 22.5% in 2012/13 and has now risen to 26–27%. He noted that this 4% increase “may not seem huge, but is a lot” and represents a relative increase of 20% over the past decade.

Blake also reported major gains in the first four or five years, which have broadly plateaued since. PD was almost solely responsible for that initial increase—jumping from 17.3% in 2012/13 to 20.8% in 2021/22, having peaked as high as 21%. Blake added that HHD has gone backwards slightly despite an early period of growth (5.4% in 2012/13; 6% in 2015/16; 5.5% in 2021/22).

“In total, the dialysis population of Ontario has risen 24% in the past decade, but ICHD has only risen 17% while home dialysis has gone up by almost 50%,” he said. “And, PD is the big driver, as it is up almost 56% while HHD is up about 30%. This gives you a sense of the change that has occurred in dialysis modality distribution across the province following the switch towards home modalities.”

While growth has slowed, almost to a halt, since the first half of the decade, Blake noted the importance of these higher rates being maintained—as many initiatives make a difference early on but ultimately fail to sustain change. In addition to reporting cost savings in the region of C$60 million, the speaker cited the develop-

Dialysis in Ontario from 2012/13 to 2021/22 Overall dialysis population =

In-centre haemodialysis rate =

Peritoneal dialysis rate =

Home haemodialysis rate =

+24% +17% +56% +30%

Peter Blake

ment of a network of accountability, the “critical” role played by renal programme directors in controlling resources and staff, and the power given to the ORN through funding control as being key, but added that it is difficult to assess the impact of individual interventions due to the fact they were all implemented concurrently across the board.

Detailing present and future challenges, Blake said growth becomes harder over time and conceded that there may be a limit to how much more home dialysis uptake can increase.

He believes the rate in Ontario, for example, is unlikely to shift above 30% without ‘compulsion’ i.e. mandating home dialysis usage. However, Blake reiterated here that he thinks these current home dialysis rates are sustainable moving forward. He also said he was “disappointed” to see HHD stagnate, adding that a “gamechanger” is likely needed here. Speaking to Renal Interventions following UKKW, Blake elaborated: “Assisted PD was crucially important in this initiative and is being used in 20–35% of patients at any given time. However, staffing shortages— especially during the COVID-19 pandemic—have been limiting availability of this support in many regions. Also, assisted PD raises costs and so care should be taken in judiciously focusing on providing it to those who truly need it.”

Blake further noted that kidney transplant rates also rose throughout the past decade— particularly prior to the COVID-19 pandemic— and this inevitably detracts from growth in home dialysis uptake, drawing some ESKD patients away from dialysis altogether. This was reflected in the ORN’s decision to drop its home dialysis target from 28% to 27% midway through the initiative.

“If a region or country wishes to grow home dialysis, the funder has to engage the providers— either with direct financial incentives...or by demanding that targets are achieved via performance management.”

Other lessons learned over the past 10 years, according to Blake, include the fact that “nephrologists alone will not grow home dialysis across a region”. And, while they are generally favourable/not hostile to increased home dialysis deployment, only a small percentage are passionate and committed to driving this change. As such, growth is more likely to depend on more widescale initiatives backed by the ‘funding lever’. Here, Blake highlighted examples, including more extreme but ultimately successful PD-first strategies seen in Hong Kong and Thailand, and the USA’s attempts to boost HHD and PD by adding drugs (a “huge profit item”) into dialysis funding bundles from 2011.

This constitutes “a very clear example of how the funder can change the game”, Blake asserted.

“The default modality selection is always ICHD, because it is easier to do [and to deliver at short notice],” Blake concluded. “If a region or country wishes to grow home dialysis, the funder has to engage the providers—either with direct financial incentives like in the USA, or by demanding that targets are achieved via performance management, as we have done in Ontario.”

UK Kidney Week

9

UK Kidney Week / Dialysis

Kidney disease inequality of “profound concern” for UK healthcare systems Current inequalities in kidney disease outcomes represent a “profound concern” for the UK and must be addressed moving forward, according to UK Kidney Association (UKKA) president Paul Cockwell (Queen Elizabeth Hospital, Birmingham, UK). Speaking to Renal Interventions at this year’s UK Kidney Week (UKKW; 7–9 June, Birmingham, UK), he also discussed highlights from the event’s three-day programme, and the “criticality” of cross-speciality collaboration—another key theme observed throughout UKKW 2022.

COCKWELL GAVE A NOD TO A UKKW plenary session that saw current director of the University College London (UCL) Institute of Health Equity Michael Marmot deliver “incredibly concerning” data showing worsening survival rates among UK kidney disease patients—a trend that is even more noticeable among poorer socio-economic groups and certain ethnic minorities. “These disparities are of profound concern and, of course, people with kidney disease are overrepresented in those groups,” he added.

“There has been a lot of discussion this week about what we [the UKKA] need to do as an organisation to really focus on inequalities,” Cockwell said. He noted that, following UKKW, he and a number of other people have committed to “pulling together” the various groups who care for kidney disease patients in the UK— from patient charities to research funders—to build a nationwide collaboration that can “make the case for major investment in addressing inequalities”.

Changing systems “Another strong, unifying theme at the meeting has been the criticality of groups working together across speciality areas,” Cockwell continued, “so that we move away from ‘silo working’. In looking after people with kidney disease, we are really looking after people with a range of long-term conditions—and we need

to find a way to work across speciality areas, to be able to work into primary care, and to identify people who are at risk of developing kidney disease earlier on in the pathway.”

Cockwell also stated that, when it comes to kidney disease, early intervention is vital, as it improves outcomes at an individual level, and also at a population level in terms of ensuring value for the system. “The systems are changing, particularly in England, to integrated care boards, which are responsible for delivering health and social care at a smaller population level,” he noted. “There are also changes taking place in the NHS [National Health Service] in the devolved nations as well, and what this means is that local kidney teams have to work as effectively and as accurately as possible in a really

Paul Cockwell

In the future, the UK Renal Registry (UKRR) is hoping to build up a greater wealth of information on what happens to kidney patients before they begin renal replacement therapy (RRT), with a view to understanding why some patients opt out of receiving RRT in the first place, among addressing other currently unanswered questions.

T

UKKW highlights Drawing out other highlights from a “fabulous” UKKW, Cockwell touched on the plenary session from Thursday 9 June, which saw UK Medicines and Healthcare products Regulatory Agency (MHRA) chief executive June Raine discuss the MHRA’s efforts to fast-track treatments through approval processes during the COVID-19 pandemic—but also, more generally, to ensure regulatory pathways are as tight as possible so that new treatments can reach patients in a timely fashion.

Having been presented as this year’s O’Donoghue Lecture, this provided a fitting tribute to the late Donal O’Donoghue and his contributions to UK renal medicine, according to Cockwell. These contributions, and O’Donoghue’s “incessant focus” on inequality and supporting multi-professional teams, Cockwell added, were also closely aligned with the core themes of UKKW 2022. Finally, he highlighted the “outstanding”, Raine Award-winning lecture given by Jennifer Lees (University of Glasgow, Glasgow, UK), which featured international competitive research that “really improves our understanding of what happens to people with kidney disease—in terms of cancer risks, how we measure kidney function, and how we map that onto a higher risk of poor outcomes, to identify those patients who really need enhanced care to protect their health in the longer term”.

“Another strong, unifying theme at the meeting has been the criticality of groups working together across speciality areas, so that we move away from ‘silo working’.”

UK Renal Registry hopes to shed light on pre-RRT factors in future

his is according to James Medcalf (University of Leicester, Leicester, UK), who is the medical director for the UKRR. “At the moment, the vast majority of data we have are about people who have reached that point of either having dialysis or undergoing transplantation,” Medcalf told Renal Interventions. “But we know that there are a lot of people—particularly in the UK—who would actively choose not to have RRT.”

short timeframe to make the most of any new resources coming into their systems.”

Medcalf noted that many of these patients will instead decide they want to receive ‘conservative care’, whereby the focus shifts from traditional kidney disease treatments to prioritising symptom control and preserving quality of life.

“We do not currently know a great deal about those people, but we are hoping that by understanding more about them we can get better answers on [their outcomes] in the future,” he added.

Discussing the recent UKRR report,

which featured data on RRT up to 31 December 2020, Medcalf said that “sadly”, but “expectedly”, the majority of its findings were heavily influenced by the COVID-19 pandemic. “This year, for the first time, we had a levelling off in terms of the number of new people starting on dialysis or being transplanted,” he continued. “That is despite years of steady upward growth [before 2020].”

Medcalf also noted, however, that a decline in the rate of kidney transplantations was offset, at least to some extent, by an increased proportion of RRT patients choosing home dialysis—and peritoneal dialysis (PD) in particular. “It would be fantastic to think that one of the things to come out of a desperate situation was that more people chose home therapies,” Medcalf said. “But James Medcalf there are other

possible drivers behind that change.

Patient groups are supporting the idea that, if a patient is suitable to have homebased dialysis, then that would be second best to transplantation but, nonetheless, a good option.”

He also highlighted that this push towards providing home therapies to more patients is being supported via changes within National Health Service (NHS) commissioning too—for example, by the Renal Services Transformation Programme and the Getting It Right First Time (GIRFT) initiative.

Regarding whether RRT rates are likely to recover over the coming years, Medcalf said: “Going forward, I think that the truthful thing to say is that we do not know, and only time will tell.” However, he did also allude to early indications from the UKRR’s data for 2021, which are yet to be finalised, but suggest rates of dialysis and transplantation increased once more over the 12 months following its most recent report.

Issue 4 – July 2022

10

Home Dialysis

Dialysis

UK study striving to Inter-CEPt home dialysis discrepancies before they become entrenched As highlighted by previous studies, as well as the Getting It Right First Time (GIRFT) national report on renal medicine and data from the UK Renal Registry (UKRR), there is considerable variation in home dialysis uptake across the UK and between individual centres. The Inter-CEPt study was launched last year to assess the cause of these discrepancies and, ultimately, identify potential solutions that may help to bring nationwide home dialysis rates closer to the 20% mark recommended by the GIRFT report. With the study expected to be completed by September 2023, chief investigator Simon Davies and co-investigator Mark Lambie (both Keele University, Keele, UK) discuss the study’s significance and provide a midway update.

Briefly, what is the overall goal of the study and why was it devised?

Lambie: We know that patients treated at some units are more likely to benefit from home dialysis than patients at other units, with a range from less than 10% at the lowest level up to 35% at the highest level. This is a good example of ‘unwarranted variation’—an issue that occurs in all healthcare systems, where there are different outcomes for patients that are due to differences in culture and practices between provider units.

Furthermore, we know that particular patient groups are also less likely to be able to access home dialysis, including patients from ethnic minority backgrounds or socio-economically deprived groups. The goal of the study is to address this variability in access to home dialysis and provide some evidence-based recommendations to address this.

Why is this goal important within kidney care in the UK? Lambie: There is a lot of interest in this topic at the moment, with the GIRFT report including a target that all units should have more than 20% of patients on home dialysis. The National Kidney Federation is running a campaign to increase access to home dialysis and Kidney Care UK has been supporting units with Home Dialysis Roadshows. There are numerous reasons why this area is so important, but the biggest reason is that home dialysis allows patients to fit dialysis in around their lives, which is the best way to support ‘life participation’, an issue highlighted by the patients in the SONG-PD project.

Inequities in healthcare are a major problem nationally, and inequity in access to home dialysis is a clear example of an issue that has to be addressed with renal medicine. Home dialysis

also has benefits for the healthcare system overall, in that it will improve patient outcomes at the same time as being less costly, which will help to minimise the increasing expenditure necessary for the growing dialysis population.

Could you summarise the study design and any other key details?

Lambie: The study has several phases. The first is an ‘ethnographic’ study, where independent observers witness the process leading up to home dialysis in different units with generally good levels of home dialysis. This allows the observers to identify any practices that may be difficult to see from within the unit. There is also a survey that has now been distributed to all English renal units and contains details of all issues thought to affect home dialysis usage, along with insights from the ethnographic study and patient groups. The survey results will be matched to data from the UK Renal Registry, allowing us to identify which processes associated with the patient pathway really do seem to have a substantial impact on home dialysis usage. This will in turn inform a health economic study, which will then inform a consensus process where all stakeholders are brought together to develop a bundle of interventions and recommendations.

Have you observed any challenges or barriers facing the study since its inception?

Lambie: The most obvious challenge we have faced is COVID-19. This has changed the way some units have practiced in relation to home dialysis, but as yet we do not have a clear picture of how—nor do we know the impact of these changes. We have therefore had to adapt our analysis plans, and will have to stage our analysis

“Early findings have really emphasised the importance of the huge trust patients and their carers put in the dialysis units when opting for home therapies.”

Simon Davies

July 2022 – Issue 4

“There are numerous reasons why this...is so important, but the biggest is that home dialysis allows patients to fit dialysis in around their lives.”

Mark Lambie

into ‘pre-COVID’ and ‘COVID’ phases. It has also delayed the start of the study in that the ethnographic work could not start until researchers were able to physically go into units to witness clinical practice.

Could you provide an update on the study thus far?

Davies: Despite the challenges with COVID, we have been able to make substantial progress with the first phase of the study—the in-depth ethnographic research, which we are undertaking in four centres across the UK. We are indebted to the way they have responded to our requests to study their processes around home therapies.

They were chosen because they have a better track record than the majority of English dialysis providers and also because they represent different geographical regions and ethnicities, and include both transplanting and non-transplanting sites. We have interviewed staff, patients and carers as well as observing multidisciplinary team meetings. We will finish this part of the research in the coming weeks. The unit survey was launched at UK Kidney Week (UKKW; 7–9 June 2022, Birmingham, UK) and we hope that all centres will have completed their sections by the end of the summer.

Are there any early observations or findings you can share?

Davies: Although recruitment to the ethnographic work was tough—and a little lower than initially planned—the messages coming through from this work are looking clear enough for us to be able to draw conclusions from a reduced sample size. Early findings have really emphasised the importance of the huge trust patients and their carers put in the dialysis units when opting for home therapies. We are now exploring just what it is that centres do to earn that trust. There is much further analysis to be done, but it is clear that the ability of the centre to support individuals—which includes access to psychological and social care support—is key.

Could you expand on the nature of the intervention bundle that plans to follow the study?

Davies: The intervention bundle will be informed by published literature, and ethnographic and survey findings, and we are using the ‘capability, opportunity and motivation for behaviour change’ (COM-B) framework to ensure that all aspects are covered. What we already know is that it will be wide-ranging and must come with some fiscal levers—this is already clear from the published literature. This is where our health economic analysis comes in. It will inform commissioners both of how the finances of home therapies do (or do not) work, and also point to which aspects of the bundle will be most cost-effective.

What do you think the short- and long-term impacts of Inter-CEPt are likely to be on UK dialysis care?

Davies: In the short term, we hope that InterCEPt will provide our commissioners and clinical colleagues with the tools that will help them reach the proposed target of 20% of people on home therapies. Achieving this goal will be critically dependent on reducing the large variation on home therapy uptake that currently exists between centres. In the longer term, we hope to see that ethnicity and socioeconomic status are not of themselves barriers to home therapies, and that each and every person facing dialysis feels well-supported in making their own decision—a culture that should pervade the whole kidney unit.

Latest Advances

11

Dialysis

Research indicates peritoneal dialysis is a safe and effective modality after kidney graft loss Attendees at this year’s UK Kidney Week (UKKW; 7–9 June, Birmingham, UK) heard that—based on a recent, single-centre study—peritoneal dialysis (PD) appears to be a safe and effective modality choice for patients following the loss of their kidney graft. The study in question was presented by Shingai Pepereke (University Hospitals of Leicester NHS Trust, Leicester, UK), who asserted that it provides evidence to support the inclusion of PD in the posttransplant decision-making process.

P

epereke began by noting that post-kidney transplant patients do not tend to have the same access to the advanced, multidisciplinary care they would have had prior to first receiving renal replacement therapy (RRT). Global registry data indicate that somewhere between 2% and 18% of patients initiate PD after graft loss—meaning the majority go onto haemodialysis, despite existing data also suggesting similar outcomes between the two modalities.

As such, Pepereke and her team set out to assess whether PD is an acceptable

“Seven of the patients in our graftloss group went on to be transplanted again, which shows that PD was successfully used as a bridge to further retransplantation.”

Shingai Pepereke

modality after graft loss via a retrospective, observational, single-centre study, which took place from January 2012 to January 2022 and included 52 patients.

She told the UKKW audience that the study’s goal was to ultimately inform quality improvement processes, optimise RRT planning and improve outcomes for post-transplant patients. The study also assessed PD infection risks while continuing low-level immunosuppression and evaluated the impact of continued immunosuppression on preserving residual kidney function, Pepereke detailed.

Discussing peritonitis occurrence, she noted that the rate of infection in the prior transplantation group (0.4 per year) was slightly higher than that seen in a non-transplantation group derived from historical cohort data over the same time period (0.3 per year). Pepereke also reported that the technique survival rate in the graft-loss cohort was slightly lower as compared to the overall PD patient population, but patient survival was “very similar” between the two groups at 92% and 91%, respectively. “Seven of the patients in our graft-loss group went on to be transplanted again, which shows

Quanta Dialysis Technologies wins top UK engineering innovation award QUANTA DIALYSIS TECHNOLOGIES has received the 2022 MacRobert Award in recognition of its efforts to develop the SC+ system—a portable, easy-to-use, high-performance dialysis machine intended to allow greater flexibility across the care continuum.

The team behind this compact dialysis machine, which was designed to enable kidney failure patients to treat themselves at home and relieve pressure on over-stretched hospitals, was named by the Royal Academy of Engineering as the recipient of the UK’s longest-running and most prestigious engineering innovation award, according to a Quanta press release.

The award celebrates engineering developments that demonstrate outstanding engineering innovation, commercial success and tangible social benefits—and the SC+ haemodialysis system impressed judges across all three criteria, the release adds.

“It is already having a dramatic impact on patient quality of life, as it is easier to operate, faster to train on and as powerful as traditional in-centre dialysis machines,” a statement from the Royal Academy of Engineering notes. “This flexibility also enables patients to

treat themselves at home overnight, receiving more dialysis care than they would in clinical settings and eliminating the gap where patients go without dialysis over a weekend.”

Quanta is already working with National Health Service (NHS) trusts in the UK and, during COVID-19 lockdowns, provided its entire UK SC+ system stock to the NHS in order to relieve pressure on hospitals and intensive care units.

Judges for the MacRobert Award were also impressed by the enormous commercial potential held by the device, the release continues. The SC+ is already US Food and Drug Administration (FDA) cleared and, in 2021, Quanta raised US$245 million to fund the rollout of the SC+ system in the USA— which it claims is the largest-ever private funding round for a dialysis device company.

The Quanta team was announced as the award winners at the Royal Academy of Engineering’s Awards Dinner in London on Tuesday 12 July and received a £50,000 prize.

that PD was successfully used as a bridge to further retransplantation,” she added.

The speaker also stated that the rate of decline in glomerular filtration rate (GFR) was used to measure decreasing residual kidney function, with a decline of 1.6ml per minute, per year, being observed in the prior-transplant patients, compared to a “quite comparable” rate of 1.87ml per minute, per year, in those who had not previously had a transplant. Pepereke then relayed that her team’s research demonstrated similar results to two major registry studies, from the USA and France, that have been conducted to date, achieving comparable one-year patient and technique survival rates despite featuring a slightly older patient cohort.

“We were able to demonstrate that PD is a safe and effective dialysis modality after graft loss,” she concluded. “And, while peritonitis rates may be slightly higher when compared to the whole PD population, they are still [in line] with the updated ISPD [International Society for Peritoneal Dialysis] 2022 guidelines, which say a risk of 0.4 episodes per year is acceptable.

“We feel that the presence of a renal allograft really should not preclude percutaneous catheter insertion—in fact, it brings advantages, because a lot of these patients will be at a higher risk under general anaesthesia due to their comorbidities. Ultimately, [these findings are] encouraging in showing that PD should be included as part of shared decision-making when we are planning dialysis modality choices in patients approaching renal allograft low clearance.”

Air pollution exposure may heighten risk of heart disease among US adults receiving haemodialysis

SC+ system

IN A RETROSPECTIVE COHORT STUDY PUBLISHED IN THE American Journal of Kidney Diseases, researchers have found that US adults receiving haemodialysis who are exposed to higher levels of air pollution have more heart attacks and strokes compared to haemodialysis patients with low levels of exposure. The strongest associations of air pollution exposure with cardiovascular events were noted among patients who were Asian, older, or had chronic lung disease at dialysis initiation, according to the researchers.

Led by Yuzhi Xi (University of North Carolina, Chapel Hill, USA), researchers conducted an epidemiological study to assess the association between annual PM2.5 exposure, and cardiovascular events and death, among patients receiving regular outpatient haemodialysis in the USA between 2011 and 2016. A total of more than 314,000 kidney disease patients were identified in the United States Renal Data System (USRDS).

They found a higher risk of heart attacks, strokes and related events in patients receiving maintenance in-centre haemodialysis who were exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older (≥75 years) at the start of dialysis, Asian, or had chronic obstructive pulmonary disease.

The researchers note that these findings “bolster the evidence base linking air pollution and adverse health outcomes, and may inform policymakers and clinicians”, and state that exposure mitigation on an individual level could be beneficial to at-risk patients.

Issue 4 – July 2022

12

Profile

Q&A

Aisha Shaikh Aisha Shaikh’s career in general and interventional nephrology has seen her assume leading roles in vascular access clinics, dialysis units and transplant centres alike, caring for a wide variety of kidney patients in different settings and locations across the USA. Shaikh is currently an adjunct associate professor of Medicine and Nephrology at Mount Sinai’s Icahn School of Medicine and an associate clinical member at Memorial Sloan Kettering Cancer Center (both in New York), and the co-chair of the American Society of Diagnostic and Interventional Nephrology (ASDIN) Training and Workforce Committee. She is also an active participant in the nephrology community, as a member of the American Society of Nephrology (ASN), National Kidney Foundation (NKF) and American Society of Onconephrology (ASON).

Here, Shaikh discusses all this and more, including a number of hot topics in the kidney care space, with Renal Interventions.

What initially attracted you to medicine, and the field of nephrology in particular?

As a child, I was in awe of doctors. I thought medicine was magic and doctors were magicians.

When I was very young, I witnessed my mother receive treatment for and be cured of tuberculosis (TB), an illness that would have been fatal without anti-TB therapy. Anti-TB therapy is nothing short of a medical miracle. As I grew older, medicine became an obvious career choice for me. Practising medicine requires an understanding of science, puzzle-solving skills and an ability to interact with vulnerable people with illnesses—a challenging and stimulating combination.

In medical school, my first clinical rotation was in nephrology. During that rotation, I had the opportunity to observe a kidney transplant surgery. I was in absolute awe; the sight of the kidney producing urine within a few minutes of being transplanted into the patient was nothing short of a miracle to me. Once again, it felt that medicine was magic. I was struck by how good nephrologists were at solving complex medical problems. By the end of my nephrology rotation, I wanted to be a nephrologist.

Who have your mentors been and how have they influenced your career?

I have been very fortunate to have outstanding July 2022 – Issue 4

nephrologists as my mentors, including William E Mitch, Rajiv Kumar, and Nelson Leung, who shaped my career. Something that they all have in common is an insatiable curiosity and a relentless desire to learn. I try to incorporate the lessons I have learned from them into my clinical practice.

How did your time in the US Department of Veteran Affairs impact your career in medicine?

I was the renal service chief and medical director of the Veteran Affairs (VA) dialysis unit for four years. During this time, our team made numerous changes in the structure of the renal programme to provide better care to the veterans. We created a dedicated vascular access team to monitor and treat vascular access issues in a timely manner. We lowered the dialysis catheter rate and increased the arteriovenous access rate among haemodialysis patients. During the COVID-19 pandemic, we were among the first haemodialysis units in the USA to administer COVID-19 vaccines to the veterans. The most important lesson I learned during my time at the VA was that, as physicians, we must fiercely advocate for the veterans and their needs. The veterans are the best among us and deserve the best from us.

Having worked in vascular access clinics, dialysis units and transplant centres, where do you think the most significant challenges lie in the treatment of kidney disease?

Educating nephrologists and the dialysis staff about dialysis vascular access care is critical in improving vascular access outcomes. High staff turnover in dialysis units is a massive challenge, as staff training requires time and effort. I have worked in several dialysis units in rural and urban settings. Access to care is a huge issue in rural areas where patients may have to drive for several hours for a dialysis vascular access procedure or a kidney transplant evaluation. These barriers can restrict patients’ access to care and prevent them from pursuing appropriate therapeutic options.

Why are professional organisations like ASDIN and ASN needed in the kidney care space?

ASDIN and ASN must continue collaborating with other professional societies, organisations and patient advocacy groups to advance kidney disease care. They must advocate at the legislative level to promote clinical care and research funding for kidney diseases.

What do you feel has been the most important development in the field of nephrology during your career?

Recognition of the benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in diabetic and non-diabetic chronic kidney disease (CKD), understanding of the genetics of kidney disease using genome-wide association study, creation and utility of endovascular arteriovenous fistula in haemodialysis patients, use of novel therapies to reduce glucocorticoid exposure in glomerular diseases, and elimination of race from the estimated glomerular filtration rate (eGFR) calculation, represent important developments in the field of nephrology during my career.

Could you outline one particularly promising piece of research you are currently involved with?

Our group was among the first to report prolonged SARS-CoV-2 polymerase chain reaction (PCR) positivity in haemodialysis patients with COVID-19. We were also among the first to report the antibody response to the COVID-19 vaccine in haemodialysis patients. These studies were critical in expanding our understanding of SARS-CoV-2 infection and vaccination in the dialysis population, as there were no existing data on the novel SARS-CoV-2 virus. Currently, we are studying the impact of various cancer therapies on kidney function too.

Besides your own work, what is the most interesting piece of nephrology research you have seen in the past year?

I would say that the EMPA-KIDNEY trial is the most impactful trial in nephrology that will (hopefully) be published in the next few months.

This trial was stopped early due to positive efficacy observed in the SGLT2 inhibitor arm. SGLT2 inhibitors have changed the landscape of diabetic and non-diabetic kidney disease management, and now we have tools to slow the progression of CKD. EMPA-KIDNEY will provide further insight into kidney disease patients who are more likely to benefit from SGLT2 inhibitors.

What are the most significant unmet needs in onco-nephrology right now—and how might they be resolved?

In my view, excluding patients with CKD from major cancer clinical trials is a significant prob-

Fact file Current appointments: Adjunct associate professor of Medicine/ Nephrology, Icahn School of Medicine at Mount Sinai, New York, USA Associate clinical member, Department of Medicine/Renal, Memorial Sloan Kettering Cancer Center, New York, USA

Education: 1999–2000: Internship in Medicine and Surgery, Aga Khan University, Karachi, Pakistan 2002–2005: Residency in Internal Medicine, University of Texas Medical Branch, Galveston, USA 2005–2008: Fellowship in Nephrology and Hypertension, Mayo Graduate School of Medicine, Rochester, USA 2008: Interventional nephrology training, Lifeline Access Center, Wichita, USA

Honours (selected): 2005: Thomas N & Gleaves James Award for Excellent Performance by a Third Year Resident in Internal Medicine, University of Texas Medical Branch, Galveston, USA 2008: Nephrology Fellowship Outstanding Achievement award, Mayo Graduate School of Medicine, Rochester, USA 2017: Teaching Attending of the Year award, Icahn School of Medicine at Mount Sinai, New York, USA 2017–2021: Chief of Renal Division and Renal Transplant Center, James J Peters Veterans Affairs Medical Center, New York, USA 2022–present: Co-chair of American Society of Diagnostic and Interventional Nephrology (ASDIN) Training and Workforce Committee

Profile

lem. Inclusion of patients with kidney disease in clinical trials is essential to formulate an evidence-based approach for cancer treatment in patients with CKD. Additionally, we need better collaboration between the nephrology and oncology professional societies to develop clinical practice guidelines and design clinical trials.

Looking back over your career, could you describe one particularly memorable case or patient, and why it has stuck with you?

My most memorable patient is Susan (not her real name), who has end-stage kidney disease (ESKD).

Her son with special needs also has ESKD and is on haemodialysis. As a nephrologist, I took care of Susan and her son. Despite her own health challenges, Susan was always there for her son.

I was struck by her resilience and commitment to her son. When I relocated from Kansas to New York, Susan often sent me cards and letters as she was concerned about my wellbeing. People like Susan remind me that, no matter how tough life gets, one can always be kind to others.

What advice would you give to people embarking on a career in the field of nephrology?

This is an exciting time to embark on a career in nephrology. We are witnessing a surge in research and innovation that will inevitably lead to better

Illustration by: Andy Watt / NB Illustration

“In my view, excluding patients with CKD from major cancer clinical trials is a significant problem.

Inclusion of patients with kidney disease in clinical trials is essential to formulate an evidence-based approach for cancer treatment in patients with CKD.”

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therapeutic options for patients with kidney disease. My advice to the fellows would be to enjoy the training process; the ups and the downs will teach you a lot. Find a mentor early in your training, and do not be afraid to explore different career paths. At the end of the day, you must find joy in what you do, and greatness will follow.

What are your interests outside of the field of medicine?

My interests outside of medicine include travelling, cooking, and watching real-life crime shows.

My most memorable travel experiences include Japan, Peru and New Zealand. I climbed Mount Fuji in Japan, hiked Machu Picchu in Peru, and visited Lake Crucible in New Zealand. I highly recommend the Salkantay trek to Machu Picchu, as it is far more scenic than the Inca trail. In addition to travelling and exploring nature, I enjoy cooking and oddly find it very relaxing. If you follow me on Twitter (@aishaikh), you have probably seen the food pictures that I often post. Lately, I have developed an interest in food presentation, and the art of food plating. It is famously said that we eat with our eyes, which makes food presentation so essential and enjoyable! Another favourite pastime of mine is watching real-life crime shows— which, I must admit, is not as relaxing as travelling and cooking but is fun nevertheless!

Issue 4 – July 2022

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VASA

Fistula ligation “should become a routine part of post-transplant care” At this year’s Vascular Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA), Alexander Toledo (University of North Carolina, Chapel Hill, USA) asserted the advantages of selectively ligating a patient’s arteriovenous fistula (AVF) following a successful kidney transplant— citing long-term medical, practical and cosmetic benefits.

T

oledo began by noting that the average kidney graft survival time is 12–20 years for living donor transplants and 8–12 years for deceased donor transplants—and the most common reason for these grafts failing is the patient passing away, leading him to note that, “one way or another, most of our transplant patients will never need their dialysis access again”.

Listing factors that nephrologists and transplant surgeons may look at before deciding to ligate or preserve a fistula, the speaker said previous rejection episodes, presence of donor-specific antibodies and creatinine stability, as well as AVF characteristics like flow rate and whether the patient has other potential sites in case dialysis access is required in the future, may all be weighed alongside the likely lifespan Alexander Toledo of the kidney graft.

However, there is an absence of concrete guidelines on how to manage AVFs post-transplantation, he continued. “We are left with this conundrum: do we want to ligate the fistula, or preserve it?”

Toledo said, noting that the possible benefits of ligation include reducing high flow through the access and lower-

ing cardiac output. “These fistulas do put some degree of strain on the cardiopulmonary system and, if we do not need them, maybe the best approach is to ligate them,” he noted.

In addition to the risk of rupture that an open fistula carries, Toledo detailed a number of quality-of-life considerations from the patient’s perspective, including cosmetic advantages, reduced pain, and general improvements in their ability to work, play sports and go about their daily lives uninhibited. He did, however, also allude to the potential advantages of AVF preservation, namely maintaining the option for future haemodialysis access. Citing a study he and his colleagues carried out, Toledo also said that, while cost and surgical risk associated with ligation were minimal, these factors are “always a consideration in modern healthcare”.

The study in question involved more than 700 patients—52 of whom had their fistulas ligated post-transplantation and were followed up for a minimum of two years. “We looked at the indications for why we were ligating these fistulas,” he relayed, “and we found that

only four of them were for strictly medical or cardiopulmonary reasons, such as high-output heart failure or a deep, excessive oedema of the arm.

“The vast majority of [ligations] were patient-driven.

Some were caused by pain with the aneurysm or swelling in the arm, but there were also a lot of underrepresented factors that we do not traditionally consider when deciding if we want to ligate a fistula.” Toledo reiterated that cosmetic issues, including being able to wear shortsleeved clothing; job-related factors, like being able to perform manual labour or work in a kitchen without needing protective gear; and a desire to play with their children or return to contact sports, were all patient-reported factors in the study.

And, moving on to the outcomes of this study, the speaker stated that—in the properly selected patients— there were no returns to dialysis, episodes of readmission or any short- or long-term surgical complications. He did note, however, one reoperation that was required for arterial aneurysm development at two years, and three cases of neuropathy/pain, post-ligation.

Discussing future directions, Toledo highlighted artificial intelligence (AI), such as iBox (Cibiltech) and other emerging technologies, as a promising tool for stratifying post-transplant ligation candidates. He noted that these findings also point towards the importance of patient education regarding fistula management post-transplantation—as well as the potential role for personalised medicine in vascular access—and said that longer-term follow-up with a larger patient cohort is of interest too.

“Again, many of these post-transplant patients are not going to need their fistula or graft,” Toledo concluded.

“There are potential medical benefits to AVF ligation and patient input is a valid consideration. I do believe this should be a routine aspect of post-transplant care— and, much further down the road, perhaps we will even have some criteria or guidelines that we can use.” In the interim, Toledo said he relies on the factors mentioned above and his transplant nephrology colleagues to make individualised decisions with post-transplant patients regarding ligation or preservation of their fistula.

“These fistulas do put some degree of strain on the cardiopulmonary system and, if we do not need them, maybe the best approach is to ligate them.”

Results from VasQ external support comparative US study presented for the first time A LAMINATE MEDICAL TECHNOLOGIES press release reports that the US VasQ external support comparative study results were recently presented for the first time globally at the 2022 Vascular Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA).

The study was a propensity-score matched comparison of the VasQ US pivotal study singlearm prospective data with untreated contemporary Medicare patients who underwent arteriovenous fistula creation for haemodialysis by the same study surgeons. According to a company press release, the study results demonstrated a significant improvement in primary patency and fistula usability with less reintervention burden within the first six months post-creation.

C Keith Ozaki (Brigham and Women’s Hospital, Boston, USA), the local principal investigator for the phase 3 pivotal study, stated: “The results July 2022 – Issue 4

VasQ device

of this carefully performed analysis clearly link higher patency, lower reintervention rates, and increased haemodialysis access usability with the VasQ device. These data support similar results from multiple European studies on VasQ’s ability to reduce intervention burden on haemodialysis patients.”

The data release at VASA builds on previous VasQ US pivotal study data releases, first by Ellen Dillavou (WakeMed, Raleigh, USA), who reported at the VEITHsymposium 2021 (16–20 November, Orlando, USA) that VasQ met the primary effectiveness performance goal, and second by John Lucas III (Greenwood Leflore Hospital, Greenwood, USA), who reported at the Charing Cross (CX) Symposium 2022 (26–28 April, London, UK) high secondary patency rates at two years as compared to published contemporary US meta-analyses.

Dillavou added: “The mounting volume of evidence for VasQ continues to support the adoption of this technology as standard practice for access creation in order to give our patients the best chance for successful dialysis with a fistula and expediting removal of central venous catheters.”

Laminate Medical Technologies advises in the release that VasQ is currently under review by the US Food and Drug Administration (FDA) for market clearance and is not available for sale in the USA at the time of this announcement.

VASA

Flex Vessel Prep system shows favourable six-month results compared to historical data NEW DATA PRESENTED AT THE 2022 VASCULAR Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA) have demonstrated favourable outcomes with the Flex Vessel Prep system as compared to historical data, and “really impressive” results in the cephalic arch and in arteriovenous grafts (AVGs), according to a VentureMed Group press release.

The release also notes that this indicates a longer-lasting solution, as compared to standalone percutaneous transluminal angioplasty (PTA), in the treatment of arteriovenous fistulas (AVFs) and AVGs. Findings from the FLEX Vessel Prep AV registry—a single-arm, prospective study conducted with 114 realworld patients across eight

US centres—were delivered by primary investigator and Vascular Access Society of the Americas (VASA) president John Aruny (Dialysis Access Institute, Orangeburg, USA).

“Arteriovenous access failure is a significant issue for patients that interrupts lifesaving haemodialysis treatments, so physicians are always searching for new options to extend time between interventions,” said Aruny. “The FLEX AV registry six-month outcomes demonstrate sustained patency across most patients and really impressive results in the cephalic arch and AVGs over treating with PTA alone.”

Six-month functional patency and freedom from target lesion revascularisation (FFTLR) results with Flex Vessel Prep are as follows:

A patency of 71% for all AVF patients—219 days FFTLR, compared with historical data ranging from 21.3 to 55% A patency of 69% for cephalic arch lesions—211 days FFTLR, versus historical data of 8–52% A patency of 47% for all AVG patients—174 days FFTLR, compared with historical data of 6–34% The VentureMed release also details that the Flex Vessel Prep procedure demonstrated excellent safety in the AV registry, with no serious adverse events reported.

This AV registry also set a new standard for patient diversity and inclusivity, the release continues, as more than 65% (75/114) of the patients enrolled were African American.

The six-month safety and patency results for African American patients treated with Flex Vessel Prep were equal to or better than the total patient pool for all recorded measurements.

“The FLEX AV registry six-month outcomes demonstrate sustained patency across most patients and really impressive results in the cephalic arch and AVGs over treating with PTA alone.”

John Aruny

Policy adherence and patientcentred thinking both vital in enabling self-cannulation

I

t is critical that clinicians follow—or, at the very least, are aware of—their centre’s policies regarding cannulation practices.

This message was delivered by Deborah Brouwer-Maier (Transonic Systems, Ithaca, USA) during a presentation at the 2022 Vascular Access for Hemodialysis Symposium (VASA; 9–11 June, Charleston, USA), who also addressed challenges in self-cannulation and asserted: “We have to stop thinking about how we do it, and we have to start thinking about how we would do it if we were that patient in the chair.”

Addressing an audience largely composed of vascular surgeons, interventional radiologists and nephrologists, Brouwer-Maier said: “As physicians, most of you have the ability to do what you think is right based on your medical judgement. As a nurse and a patient care technician, I must practice under the policy and the procedures of the facility that I work at—I do not

Deborah Brouwer-Maier

have the autonomy to go outside of that scope.

“I am depending on corporate and local hospital policies, and the physician order, to allow me to practice. Patient care technicians practice under my nursing licence because I am overseeing them, and that is why the policies and procedures are so important. If you have not reviewed the cannulation policy of the facilities that you are sharing patients with, I encourage you to do that.”

Here, the speaker reiterated that she cannot deviate from these policies, but detailed how clinicians can go about initiating change if they want to do something differently in their practice. “You have to get the specific policy updated—you must go to the local governing body for the dialysis facility and get the new policy fully approved,” she said. “You can alter a corporate-level policy at the local level. A medical director has that right.”

Brouwer-Maier also emphasised that there are several significant practical differences between in-centre access cannulation, which is performed by a healthcare professional, and ‘self-cannulation’, whereby the patient has to needle their own access—often because they are dialysing at home. “In centre, the staff member can use both hands, they are at a different position and a different angle, and they can visualise it differently,” she said. “The self-cannulator has to cross their own body to cannulate and do everything one-handed, including taping and needle removal. There is also the issue of feedback: when I cannulate, I do not know if I am infiltrating until the patient tells me they feel pain. A self-cannulator feels that immediately.”

Approaches to needle taping should be

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“We have to stop thinking about how we do it, and we have to start thinking about how we would do it if we were that patient in the chair.”

covered by the aforementioned policies, Brouwer-Maier continued. Due to the fact that taping techniques vary by facility, an American Nephrology Nurses Association (ANNA) taskforce convened in 2020 to update existing information and resources relating to venous needle dislodgement and access-bloodline separation. And, while this taskforce identified five standard ways to tape, Brouwer-Maier noted that, “if you are going to do this at home, you probably cannot use the same technique that is used in-centre”. Similarly, she informed the audience, distinctions between cannulation methods like the rope-ladder and buttonhole techniques should also be outlined in the facility’s policies and procedures, adding: “Area puncture is never an appropriate cannulation method.”

Another important consideration relates to device-created arteriovenous fistulas (AVFs), she stated, as the cannulation zone is in a different location for fistulas created using the Ellipsys (Medtronic) or WavelinQ (BD) systems, when compared to more traditional, surgical AVFs. “If the patient is dialysing with their arm out […] and they are trying to do things one-handed, including responding to the dialysis machines, we need to take care to place needles in such a way that they can have some arm movement,” Brouwer-Maier continued.

The speaker concluded by outlining key dilemmas for clinicians to consider regarding self-cannulation: “Can the patient or their care partner see the access properly? Are they able to determine the angle—if you tell a patient 20 degrees, do they really understand what 20 degrees is?

And, the big problem with cannulation when you are first learning is potentially applying too much pressure to the needle. It needs a light touch, and that is hard to see when someone else is cannulating.”

While she also noted that cannulation is “a really hard thing to learn”, Brouwer-Maier highlighted a handful of innovations that can help make patients’ lives easier, including tourniquets that are intended specifically for one-handed cannulation, small clips for holding the needle in place, and even commercially available clothing designed with zippers or holes to improve access to the cannulation zone.

Issue 4 – July 2022

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Covered Stents

AVeVA study confirms benefit of covered stent placement in graft-vein anastomotic stenosis treatment

procedure demonstrated inferior TLPP rates at six months to those in non-thrombosis groups.

Dolmatch and colleagues note that reasons behind this are unknown, but the fact this was observed in their study supports the “long-suspected belief ” that a thrombosed AVG is more likely to fail due to TLPP loss, even when treated with a covered stent.

Noting secondary endpoint data, which they say should be considered observational and were calculated at predetermined intervals through the end of the study, the authors state that the Kaplan-Meier survival estimates for TLPP were 54.2% at 365 days and 36.9% at 730 days after the procedure, while Kaplan-Meier survival estimates for ACPP were 40.4%, 16.7%, and 7.8%, at 180, 365 and 730 days, respectively. A total of 91 adverse events across 53 patients (48.2%) were reported through 24 months, and 18 patients experienced device- or procedure-related events, meaning 86.3% were free from such events at 24 months.

A prospective, multicentre study involving the Covera vascular covered stent (BD) has confirmed the benefits of immediate, post-percutaneous transluminal angioplasty (PTA) placement of the device in treating arteriovenous graft (AVG) venous anastomotic stenosis when anatomically and clinically suitable.

Writing in the Journal of Vascular and Interventional Radiology ( JVIR), Bart Dolmatch (Palo Alto Medical Foundation, Mountain View, USA) and colleagues report a 30-day freedom from safety-related events of 96.4% and a six-month target lesion primary patency (TLPP) of 70.3% with the Covera stent.

Concluding messages The Covera stent did an “adequate job” of maintaining target lesion patency over time, they add, but the “marked” and “ongoing” loss of ACPP (7.8% at 24 months) indicates that—regardless of TLPP improvement with a covered stent—some AVGs may be prone to recurrent stenosis or the development of new stenoses elsewhere in the circuit. The authors state that the 24-month cumulative circuit patency rate of 73.6% further supports this notion, and the finding that TLPP was “acceptable” with covered stent placement.

The mean number of reinterventions to maintain patency was 1.6 at the treatment site and 3.6 in the access circuit at 24 months.

Dolmatch and colleagues conclude their JVIR report by noting that AVeVA was designed as “a first-in-human look at the Covera covered stent” in treating AVG venous anastomotic stenosis—and it demonstrated rates of freedom from major adverse events at 30 days (96.4%) and TLPP at six months (70.3%) that were both superior to literature-devised performance goals.

They also note, however, that AVeVA is not directly comparable with other, similar trials like FLAIR Pivotal, RENOVA and REVISE, and outline limitations of the current study, such as the inclusion of thrombosed AVGs and nontarget stenoses (rather than a more homogenous AVG group), and the potential for an “inherent bias” being created by its single-arm design and the selection of historical studies. “A comparative, powered, randomised study would be needed to determine patency differences between different covered stents within the same demographic population,” the authors add.

T

he authors begin by noting that, as per three prospective, multicentre, randomised trials, placement of a covered stent has previously led to statistically superior TLPP rates compared to PTA alone in restoring flow and maintaining haemodialysis access.

They add that the current study, AVeVA (Arteriovenous stent graft in the treatment of stenosis at the graft-vein anastomosis of AV graft circuits), examined a self-expanding nitinol covered stent (Covera) that is more flexible than the device used in two of those prior studies (Flair, BD).

AVeVA study Between August 2016 and February 2017, 110 patients were treated by investigators across 14 US centres in AVeVA—a single-arm, investigational device exemption (IDE) study without a concurrent control. Dolmatch and colleagues note that, because prospective trials of previous-generation covered stents had been completed and published, and the devices had been approved by the US Food and Drug Administration (FDA) for the indication being studied, pooled mean values from these trials as well as additional published data on the use of PTA alone for haemodialysis graft stenosis were used to develop safety- and patency-related performance goals for AVeVA. The primary safety endpoint was 30-day freedom from an adverse event involving the access circuit resulting in additional intervention, surgery, hospitalisation or death. The primary efficacy endpoint was six-month TLPP, or the interval following treatment until the next clinically driven reintervention at the site of the target lesion or until the AVG was abandoned. Prespecified secondary endpoints included acute technical and procedural success, access circuit primary patency (ACPP), cumulative patency, number of reinterventions, index of patency function (IPF), and adverse events through two years.

Of the 181 patients who gave informed consent to participate, 71 did not meet the study eligibility criteria—with 75% deemed not to have angiographic evidence of ≥50% stenosis and clinical evidence of graft dysfunction—meaning 110 patients (mean age=64.3 years, 54.5% female, mean body mass index [BMI]=28.7kg/m2) were ultimately enrolled and treated with the Covera device. The vast majority (98.2%) had an upperarm AVG. New Covera data The authors detail that the mean anastomotic lesion stenosis at the time of treatment was 71.5%, decreasing to a mean residual stenosis of July 2022 – Issue 4

21% following PTA predilation. One covered stent was used to treat each study lesion, meaning 110 stents were deployed, and all but two of these were postdilated. The mean residual stenosis at procedure completion was 0.9%, Dolmatch and colleagues report. In all cases, the covered stent was deployed to the intended location and eliminated preprocedural symptoms of access dysfunction—constituting a technical and procedural success rate of 100%. All but two patients (98%) resumed dialysis after the procedure using their AVG. At 30 days, freedom from adverse events was 96.4%. Four patients (3.6%) required additional reintervention and one patient (0.9%) underwent required/prolonged hospitalisation. The primary safety endpoint was therefore adjudged to be superior to the performance goal of 88% derived from prior studies and existing literature.

A total of 102 patients (92.7%) were available for the six-month primary efficacy analysis. TLPP at six months was 70.3% among these patients, the authors detail, and this was deemed superior to the prespecified performance goal of 40%. The only observed difference in patient subgroup analyses related to thrombosed AVGs, as those who presented with thrombosis within 30 days of the index procedure and/or at the time of the

“A comparative, powered, randomised study would be needed to determine patency differences between different covered stents within the same demographic population.”

Bart Dolmatch et al

Freedom from adverse events at 30 days =

96.4% Better than performance goal of 88%

Target lesion primary patency at six months =

70.3% Better than performance goal of 40%

Vascular Access

History warns us against “optimistic exuberance” in drug-coated balloon trials The importance of assessing clinical trial data in an objective, balanced way has been borne out by recent history in the vascular surgery space, according to Ziv Haskal (University of Virginia, Charlottesville, USA). This is particularly pertinent given the latest drug-coated balloon (DCB) breakthroughs, including three-year data from the IN.PACT AV Access trial (Medtronic), presented for the first time at the 2022 Charing Cross (CX) Symposium (26–28 April, London, UK). Haskal also warns against “optimistic exuberance” and emphasises the need to remain grounded in “durable, hard reality” when drawing conclusions from these studies.

S

peaking to Renal Interventions at the Society of Interventional Radiology (SIR) annual scientific meeting (11–16 June, Boston, USA), Haskal noted: “Industry trials are always designed to show positivity—and there is nothing wrong with that, because of the substantial stakes and costs of testing a new therapy, and a desire to define the most rarefied cohort where success and signal can be discerned. But the problem is that we naturally extrapolate the resulting data to everybody.

“And, we know that, when you continue to replicate things, signals becomes weaker over time as populations broaden or undergo further testing, or control therapies do better than expected.” On discrepancies between perceptibly positive IN.PACT AV Access results and the more maligned Lutonix AV trial (BD), Haskal outlines the possibility that—while comparatively better outcomes in the former have been attributed to drug-device superiority—the enrolled IN.PACT AV Access population may have been “honed” more effectively to show a certain signal.

PAVE trial The flipside of this, Haskal continues, is that heterogenous studies that are not industry-sponsored, such as the UK-based PAVE trial, carry “natural variability”. The

trial, in which BD played no role other than providing the paclitaxel-coated balloons used, ultimately failed to provide evidence of additional benefit with DCBs following plain balloon angioplasty in patients with arteriovenous fistula (AVF) restenosis.

Haskal believes the design of PAVE, including its less selective patient population and the fact high-pressure plain balloon fistuloplasties were performed in all cases, could have contributed to the DCB group not outperforming its comparator. “It does not degrade or diminish the UK trial,” he adds, “but, rather, it asks the question: Are we now starting to replicate

Ziv Haskal

[DCB data] in a controlled fashion, but with more representative populations?”

Discrepancies in quality between the plain balloon angioplasties that DCBs are being compared to in such trials are also an important factor to consider, according to Haskal, who says the optimal combination of proper balloon sizing, inflation time, and possibly the use of high-pressure balloons, “may, in fact, provide better results”. “Was high-quality, conventional balloon angioplasty more consistently performed in the PAVE trial?” he queries.

Lessons from history Here, Haskal draws on a previous instance of clinical data being more indicative of study design than drug-device performance. “The original sirolimus-eluting stent, Cypher [Cordis], was supposed to be the benchmark that would put drug-eluting stents onto the market,” he says. “Why did it fail? Because results with the bare metal stents it was trialled against were better than expected. The conventional therapy simply performed better.”

Haskal points out that, while limus drugs are now ironically beginning to “circle back around” in vascular access— for example, with 12-month results from the ISABELLA trial (MedAlliance), which were also presented at CX 2022—they may

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have “lost ground” due to factors that were unique to that trial, and there being no “appetite” to test them again at the time.

He also likens the real-world variability that appears to have impacted PAVE to a similar phenomenon seen in the ATTRACT trial, which “did not kill” deep-vein thrombosis (DVT) interventions but instead led to further, more concentrated studies.

“I think the theme here is the importance of not simply jumping on the newest upgrade or latest model,” Haskal notes.

“The challenge is that, having spent a long time in the field and having been through these cycles of seeing multiple generations of devices evolve, disappear and then return, you risk being viewed as recalcitrant, or resistant to embracing new technologies. Newer generations will always jump on that—but we still have to educate on [and exercise] a natural, daily cynicism and scepticism with clinical trials.”

Haskal also concludes by highlighting that, while DCB safety is now considered a “foregone conclusion” by many, the evidence base for this may be flawed, as patient numbers in studies like IN.PACT AV Access are likely too small to detect or rule out increased cardiovascular risks, “as we do not know their potential effect size”.

“The challenge is that, having spent a long time in the field and having been through these cycles of seeing multiple generations of devices evolve, disappear and then return, you risk being viewed as recalcitrant, or resistant to embracing new technologies.”

Device-created fistulas keep future options open, but are not a replacement for surgery Based on more than four years of experience in a single centre, Robert Shahverdyan (Asklepios Klinik Barmbek, Hamburg, Germany) claims that device-based arteriovenous fistula (AVF) creation “keeps future options open”, but is not a replacement for surgical fistula creation.

SPEAKING AT THE LEIPZIG INTERVENTIONAL Course (LINC; 6–9 June, Leipzig, Germany), Shahverdyan reported new outcomes from his long-term experience with the Ellipsys (Medtronic) and WavelinQ (BD) systems, as well as with more traditional, surgically created AVFs. The presenter stressed that current studies of end-stage kidney disease show an ageing patient population with an increasing number of comorbidities. Additionally, these studies highlight lengthening waiting times for a transplant, surpassing 10 years in many cases. “As vascular access creators,” he said, “we are confronted with longer dialysis needs, and with longer access needs.”

More than 500 patients were screened at his vascular access centre over the course of four years, and Shahverdyan noted that 46% were eligible for a radiocephalic surgical fistula, while 80% had a suitable perforating vein for a surgical Gracz fistula. He noted that suitability for the Ellipsys and WavelinQ systems is dependent

High flow and steal are also important factors to consider, said Shahverdyan, due to the fact that the fistulas in question are being created for long-term use. He reported seeing “practically no steal” in distal fistulas, just one case of steal with Ellipsys, and high rates of surgical steal and high flow for Gracz fistulas, particularly if on a patient’s anatomy. In the Hamburg experience, he they had a brachial artery-based anastomosis. In terms of continued, around 61% of patients had suitable anatomy assisted and secondary patency rates, the Ellipsys, radifor at least one type of device-based creation, and 23% ocephalic and Gracz fistulas all had patency rates higher had suitable anatomy for both systems. than 80% in the four-year Hamburg experience. In ShahShahverdyan noted that, over the past four years, he verdyan’s opinion, primary patency rates “are not imporhas used the VasQ device (Laminate Medical) as a standard tant”—except in cases with frequent reinterventions. of care in radiocephalic AVFs. From more than 750 creaComparing proximal forearm AVFs, and remarking tions included in the Hamburg data, 92% are here on procedure time, the presenter detailed AVF creations, with 86% of all access creations that this was “significantly shorter” for Ellipsys, having a forearm anastomosis, he detailed. and that time to cannulation was shortest for There were also around 200 device-created Ellipsys and Gracz fistulas. The number of interfistulas, 126 Gracz AVFs and 63 arteriovenous ventions per patient was “slightly higher” for grafts (AVGs). The rest were radiocephalic fistuEllipsys, but this system resulted in the fewest las—a group also including 80 snuffbox fistulas. abandoned fistulas, closely followed by Gracz.

The technical success for both surgical and Robert Shahverdyan Shahverdyan concluded by stressing that device-created AVFs was “really high”, he “we need to consider some learning curves” for relayed. In terms of physiological maturation for fistulas device-created AVFs, but also surgical fistulas, to address that were more than four weeks old post-creation, Shah- issues like kinking and torsion. He summarised that there verdyan reported a >90% rate for VasQ radiocephalic are “some differences” between the Ellipsys, WavelinQ, fistulas, and almost 90% for Ellipsys and Gracz fistulas, and surgical fistulas, but added that device-based creation while snuffbox and WavelinQ were “a little bit behind” has an “extremely low” rate of perioperative complicawith maturation rates of roughly 80%. Regarding clini- tions. Shahverdyan then reiterated that device-created cal maturation, assessed in patients whose fistulas were fistulas enable future intervention, but should be seen as subsequently used for dialysis, he reported a >90% cannu- complementary to the vascular access surgeon’s armalation success rate for Ellipsys and radiocephalic AVFs. mentarium, rather than a complete solution.

Issue 4 – July 2022

Frailty

Standardised definitions are required before frailty can be routinely assessed in clinical practice Earlier this year, a retrospective study published in the American Journal of Kidney Diseases (AKJD) came to the conclusion that “frailty may be useful for informing clinical decision-making regarding choice of vascular access”—based on findings from the United States Renal Data System (USRDS). This paper was of great interest to Nicholas Inston, Külli Kuningas and Adnan Sharif (Queen Elizabeth Hospital, Birmingham, UK), all of whom are currently working to evaluate the definition and role of ‘frailty’ in dialysis patients in the UK.

“I

f you look at general definitions of frailty, research, in particular on how we implement it they are often age-related, and frail into clinical practice.” patients are seen as being an older age There are numerous frailty assessment tools group,” says Kuningas. “But there are signs that that are currently available. The most commonly CKD [chronic kidney disease] patients tend to be used of these is the clinical frailty scale (CFS), frail at a younger age compared to the general which involves a quick visual assessment, is population, which is why having a frailty concept utilised across many different conditions and that is not based on age is important.” Inston works on a specific, grade-based system from adds: “I think the shift is away from using age as 1–9. But, according to Kuningas, the CFS is far a parameter, and towards using frailty, on the from perfect—not least because of the extent to basis that frailty is at least a functional measure— which it is left open to clinician interpretation. “It whereas age is just a number for a lot of patients.” is very subjective,” Kuningas claims. “The way I “We have some 40-year-old patients who are would assess someone may be different to how not fit for a transplant, and some 80-year-old [a surgeon or a nephrologist] would assess somepatients who are,” he continues. “If a patient one. That is the main vulnerability of it.” She also has been on dialysis for 20 years, says that the CFS only focuses on they will almost certainly be frailer physical frailty indicators, despite than somebody of the same age who the fact that frailty has numerous has not. If they have had a kidney psychological and social ramificatransplant in those 20 years of tions for patients.

ESKD [end-stage kidney disease], According to Kuningas, the relathey will probably be less frail tive overlap between frailty and than somebody who has been on sarcopaenia has led to muscle haemodialysis during that time. So, quantity and quality also being again, it is very much patient-spelooked at as a potential adjunct to cific rather than generic, and that is true patient frailty. A recent report the reason for trying to use this as a in European Geriatric Medicine measurement.” examined the association between In a Journal of Vascular Access a simple measure of muscle paper published last year, Inston thickness, via ultrasound, and and Kuningas posit that moving commonly used frailty measures. towards a standardised, effecHowever, it ultimately concluded tive method of frailty assessment that “frailty is a multifactorial chimes with the more individualsyndrome, and caution must be ised, collaborative view to vascuused in trying to screen for this lar access care outlined in the condition with a single ultrasonic 2019 Kidney Disease Outcomes measure”.

Quality Initiative (KDOQI) guideAnd, as Kuningas notes, attempts line update. They also note that a to assess frailty measurement tools universal, reproducible approach have often been conducted among to frailty scoring will likely be a patients aged 60 years and older. “key component of ongoing future This exclusion of younger people is access care”—before concluding a problem, and makes it even more that further research is required to difficult to identify a single, univeridentify criteria and scoring tools Nicholas Inston sal frailty assessment approach, that best lend themselves to the she believes. dialysis access space.

While these guidelines recommend pivoting Frailty and vascular access towards frailty, or ‘functional status’, as opposed “We know that some older patients have worse to simply using age, the definition of frailty and outcomes with fistulas, but that is still not a precisely how it should be implemented remains reason to rule out a fistula, because they [could] murky. have worse outcomes with central venous catheters and other alternatives too,” Inston Standardised definitions avers. He believes there are a number of ways Speaking to Renal Interventions, Kuningas notes in which frailty may impact vascular access that the concept of using frailty as a clinical yard- outcomes—ranging from an increased likelistick is not entirely new, having been around hood of developing steal syndrome to greater since the early 2000s, but the primary focus has risks of arteriovenous graft (AVG) infection or been on elderly patients for much of that time, breakdown. and it is only during the past five years or so that “We would also hypothesise that frail patients broader definitions involving younger patient would tolerate high-flow fistulas less well than cohorts have really come to the fore. “This has non-frail patients but, until we do the measurebeen overdue,” she says. “There is a lot we do ments, we really have no idea,” he continues. not know about frailty, and we need much more “The short answer is that we do not know for

“I think the shift is away from using age as a parameter, and towards using frailty, on the basis that frailty is at least a functional measure— whereas age is just a number for a lot of patients.”

Nicholas Inston

Külli Kuningas

Adnan Sharif

19

certain, and we cannot interpret how [frailty] will work until we start measuring it and doing more studies.”

Inston notes that another pivotal, yet unanswered question is whether frailty scoring should be performed early on in the kidney care pathway—to help adapt the longer-term treatment plan—or just for access planning. “I think doing it just for access planning may not be the right way forward,” he states.

“You need to get in early to see what a patient’s frailty is like when you are deciding on what dialysis modality they need. Are they going to be PD [peritoneal dialysis]-suitable or not? Are they going to be suitable for a transplant? That whole life-plan is based much more on frailty than age or any other parameter.”

Inston and Kuningas are also in agreement that frailty scoring, in addition to being performed early, should be done repetitively—as opposed to taking a single, one-time measurement. “I think it is also about what you are going to do about it once you have measured it,” Kuningas adds. “If somebody is pre-frail, how can we actually intervene and potentially reverse that?

It is a multi-professional approach that needs to be incorporated into all aspects of care, and followed when the patient goes onto dialysis or receives a transplant.”

FITNESS study The need for further research in this space is echoed by Sharif, who tells Renal Interventions that FITNESS (Frailty intervention trial in end-stage patients on haemodialysis) is seeking to build on the “surprising” lack of published data from the UK to date.

This randomised controlled study, he details, has enrolled close to 500 prevalent haemodialysis patients and clinically phenotyped them using a wide range of scoring systems—from the CFS, to sarcopaenia measurements, to self-reported frailty assessments. Referencing the FITNESS baseline cohort data published in the Clinical Kidney Journal earlier this year, Sharif highlights early indications that “regardless of which frailty score you use, a lot of haemodialysis patients are frail”.

“Depending on the score, it ranges from around 40–60%, and you also have a certain proportion who are vulnerable, or pre-frail, meaning you are only left with a small proportion who are not frail at all,” he continues. “While we have found that frailty is associated with a higher risk of hospitalisation and death, it is not a very good predictor of death by itself. So, I think the question is: how should we use frailty on a day-to-day basis?”

With this patient cohort now being followed for up to 10 years, more long-term data from FITNESS—relating to outcomes across different vascular access types, more in-depth hospitalisations data, and also how closely self-reported measures correspond to more objective frailty assessment tools—are expected further down the line.

Sharif notes that, save for leading work at Johns Hopkins University (Baltimore, USA) and “pockets” of research elsewhere in Europe, published data in this area remain scant. “We should probably be using frailty a lot more in our [clinical] decision-making,” he states, adding that striking a balance between the CFS and other assessments that are quicker and easier to perform, and others that take longer but involve functional measures and are therefore potentially more useful, is key.

“A lot will probably happen with frailty over the next few years, and I think it is only a matter of time before we need a consensus meeting to agree on whether we should be using frailty in patients starting dialysis, receiving vascular access, and being listed for transplantation,” Sharif concludes. “And, if so, which frailty tool do we use? I believe that is on the horizon, because there is a lot of talk about trying to establish more of a consensus moving forward.”

Issue 4 – July 2022

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New Research

Transplantation

Stanford paediatricians transplant kidneys without need for immunosuppressants

matched transplants. The protocol is relatively gentle, making it safe for children with immune disorders who are too medically fragile for a traditional stem cell transplant. And, alpha-beta T cells recover in the patient after 60-to-90 days, meaning they regain full immune function, the release states.

When Stanford physicians began caring for a handful of children with a rare immune disease called Schimke immuno-osseous dysplasia (SIOD), they realised they could meet the patients’ medical needs with a multistep approach. “SIOD includes chronic kidney disease, which ultimately requires kidney transplantation,” Bertaina explained. SIOD also causes bone marrow failure, meaning patients need a stem cell transplant to provide a new, healthy immune system. “These were unique patients in which we had to do the stem cell transplant and a kidney transplant,” Bertaina added.

Physicians at Stanford Medicine (Stanford, USA) have developed a way to provide paediatric kidney transplants without immunosuppressant drugs. Their key innovation, according to a Stanford press release, is a safe method for transplanting the donor’s immune system to the patient before surgeons implant the kidney.

T

he medical team has named the two-transplant combination a dual immune/solid-organ transplant (DISOT). A scientific paper describing the first three DISOT cases, all performed at Lucile Packard Children’s Hospital Stanford, was recently published online in the New England Journal of Medicine (NEJM).

This scientific innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ, the release details. The new procedure also rids recipients of the substantial side-effects of a lifetime on immunosuppressant medications, including increased cancer, diabetes, infection and high blood pressure risks.

The first three DISOT patients were children with a rare immune disease, but the team is now expanding the types of patients who could benefit, and their protocol received US Food and Drug Administration (FDA) approval in May 2022 for the treatment of patients with a variety of conditions that affect the kidneys.

“Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible,” said lead author Alice Bertaina (Stanford University School of Medicine, Stanford, USA).

She anticipates that the protocol will eventually be available to many kidney transplant candidates, starting with children and young adults, and later expanding to older adults. And, their innovation has another important benefit: enabling safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.

Alice Bertaina

New methods Researchers working with adult patients have performed sequential stem cell and kidney transplants from living donors in the past, the release notes. With half-matched donors, they had partial success, but patients were either unable to fully discontinue immunosuppressant drugs post-transplant or, in some cases, had unacceptably high risks of severe graft-versus-host disease (GVHD).

The Stanford paediatric team introduced refinements that greatly improve the success of the two-transplant combination, with much lower risk. Central to this is a change in how the donor’s stem cells are processed after having been removed from their body, with technicians performing alpha-beta T cell depletion to remove the type of immune cells that cause GVHD. Bertaina’s team had showed that alpha-beta T cell depletion (which she developed while working in Italy previously) makes stem cell transplants safer and enables genetically half-

Positive outcomes Each of the three children included in the NEJM report received a stem cell transplant from one of their parents, incorporating alpha-beta T cell depletion. Between five and 10 months later, after recovering from the stem cell transplant, each child received a kidney from the same parent who had donated the stem cells. One patient had a mild episode of GVHD, affecting the skin, which was resolved with medication. After the kidney transplantation, the physicians gave immunosuppressant medications to the first two patients for 30 days, then discontinued the drugs. The third patient experienced short-term side-effects from immunosuppression, including high blood sugar, and medication was discontinued even sooner.

The release details that all three patients no longer have the immune disorder—and have been living with new, fully functioning kidneys that their bodies have accepted for 22 to 34 months. “They are doing everything,” said Bertaina. “They go to school, they go on vacation, they are doing sports—they are having completely normal lives.”

Now, the Stanford team is expanding the protocol to more types of patients, including children who have had an initial kidney transplant rejection. The new FDA approval also covers several diseases causing kidney damage, including SIOD, cystinosis, systemic lupus and loss of a prior kidney transplant due to focal segmental glomerulosclerosis. Adults whose bodies have rejected an initial kidney transplant or have an immune disease that attacks the kidneys could receive DISOT in the future, and the researchers also plan to investigate how to adapt its approach to other solid-organ transplants, including from deceased donors. “That is a challenge, but it is not impossible,” Bertaina added. “We will need three-to-five years of research to get that working well.”

Machine learning fails to outperform traditional models in predicting long-term allograft outcomes A study presented at this year’s American Transplant Congress (ATC; 4–8 June, Boston, USA) found that machine learning (ML) technologies did not outperform traditional statistical models in predicting long-term kidney allograft outcomes—attaining similar prediction performances overall.

THESE FINDINGS WERE PRESENTED

by Agathe Truchot (Paris Transplant Group, Paris, France) on behalf of researchers who concluded that, in spite of the “increased use and hype around ML”, their study supports the use of more

July 2022 – Issue 4

traditional statistical approaches for prognostication in organ transplantation.

To assess the performance of traditional versus ML-based prognostic models, the researchers developed several ML algorithms and compared their predictive capability to that achieved by the iBox prognostication system (Cordis). They used a validated derivation cohort of 4,000 consecutive kidney recipients prospectively recruited at four centres in France, and three validation cohorts from Europe (n=2,214 patients), North America (n=1,537) and South America (n=671).

A total of 24 parameters, including

the time of risk evaluation, and clinical, histopathological, immunological and functional characteristics, were used to develop six ML models ranging from tree-based models to survival support vector machines and gradient boosting techniques. Their respective prediction performances were assessed with discrimination (C-index), calibration and Brier scores, and then compared to those of the iBox system.

Among the 8,422 kidney recipients included, 12.84% (n=1,081) lost their graft after a follow-up time post-transplant of 6.25 years. The median time from transplant to risk evaluation was 0.98 years.

The derivation cohort was split into a training set and a test set, and was used to develop the ML models, while the validation cohorts were used for external validation of the models.

The C-index scores at seven years postrisk evaluation in the derivation cohort ranged from 0.527 to 0.788 for the various ML model types, compared to 0.808 for the iBox. In the external validation cohorts, the best performing ML models achieved a C-index of 0.814, 0.857 and 0.884 in Europe, North America and South America, respectively, and similar scores were observed in each with the iBox. The researchers noted that ML models achieved satisfactory calibration in the derivation and validation cohorts of their study—but, overall, the traditional statistical models achieved superior performances within the derivation cohort.

Latest News

Clinical News First patient enrolled in Merit Medical’s global WRAP registry

Merit Medical has announced the successful enrolment of the first patient in its WRAP registry. This study will evaluate the clinical benefits associated with the use of the Wrapsody cellimpermeable endoprosthesis in patients receiving haemodialysis that experience stenosis or occlusion of blood vessels required for dialysis.

Dean Huang (King’s College Hospital, London, UK) enrolled the first patient in the WRAP registry. “The patients being treated with the Wrapsody cellimpermeable endoprosthesis have historically had few clinical options,” Huang said. “These patients have typically faced frequent reinterventions to maintain vessel patency, resulting in multiple procedures and hospitalisations. The WRAP registry will add to the growing body of evidence on Wrapsody’s ability to achieve durable outcomes for this vulnerable patient population.”

The WRAP registry will enrol up to 500 patients with outflow circuit stenosis or occlusion who are receiving haemodialysis at medical facilities throughout Europe, South America, Australia, and New Zealand. Clinical patient outcomes after initial placement of the Wrapsody device will be evaluated over a two-year period in accordance with the instructions for use associated with its CE certification.

The Wrapsody cell-impermeable endoprosthesis system—an expandable nitinol stent frame fully enveloped by an external layer of expanded polytetrafluoroethylene (PTFE) and an internal layer of spun PTFE with an interposed cell-impermeable layer—is also being studied under an investigational device exemption (IDE) in the USA.

Continued clinical success reported with Transit’s vessel preparation device

Transit Scientific has shared successful outcomes from multiple arteriovenous fistula and graft cases using its XO Score sheath platform—a “first-ofits-kind” metal-alloy scoring, cutting and constraining structure device— along with off-the-shelf percutaneous transluminal angioplasty (PTA) balloons.

“A patient presented with a high-grade stenotic lesion in a brachiocephalic fistula restricting venous outflow,” said Jeffrey Hoggard (Raleigh Access Center, Raleigh, USA).

“The lesion was resistant to initial treatment using a high-pressure PTA inflated to 40 atmospheres. The lesion was then treated with the XO Score device and followed by effacement of the stenosis with standard-balloon PTA inflated to nominal pressure (nine atmospheres). There was no residual stenosis and the fistula was no longer pulsatile on exam. XO Score presented a great treatment option for us where high-pressure PTA failed.”

XO Score is a thin, one-piece, metalalloy exoskeleton sheath, with up to 22 struts/grooves, that slides over

XO Score device

an off-the-shelf angioplasty balloon, and can be used in significant chronic dialysis fistula and graft cases via lowpressure inflation—after high-pressure PTA treatment has failed, in some cases. The system is US Food and Drug Administration (FDA) and CE-mark cleared to dilate stenotic material in iliac, femoral, ilio-femoral, popliteal, infra-popliteal and renal arteries, and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulas.

Natera showcases new data on Prospera and Renasight tests at American Transplant Congress Natera recently announced the presentation of data on the clinical utility of its Prospera and Renasight tests across a total of 14 sessions at the 2022 American Transplant Congress (ATC; 4–8 June, Boston, USA). This expands on 13 peer-reviewed papers that have been published over the past 12 months, demonstrating the strong performance of both assays in predicting kidney graft rejection, according to the company.

Phil Halloran (Alberta Transplant Applied Genomics Centre, Edmonton, Canada) presented new data on the latest findings of the global, multicentre, prospective Trifecta study at ATC 2022. The study demonstrated that the new two-threshold algorithm for the Prospera test—including both donor-derived cell-free DNA (dd-cfDNA) fraction and quantity—performed better than dd-cfDNA percentage alone in detecting active rejection. This analysis of the Trifecta study featured 367 fully biopsy-matched samples from 22 participating clinics in the USA and Europe.

Natera’s Prospera test leverages the company’s core single-nucleotide (SNP)-based, massively multiplexed polymerase chain reaction (PCR) technology to identify allograft rejection non-invasively, and with high precision and accuracy, without the need for prior donor or recipient genotyping. The company’s Renasight test is a germline genetic test, indicated for patients with diagnosed kidney disease, that screens for hereditary causes of kidney disease and is run from a patient’s blood or saliva sample.

Dialyze Direct publishes data indicating rapid recovery times following more frequent dialysis

Dialyze Direct has announced that its findings regarding the effect of more frequent dialysis for end-stage kidney

disease (ESKD) patients in skilled nursing facilities (SNFs) have been peerreviewed and published in Hemodialysis International.

The research determined that more rapid post-dialysis recovery time (DRT) occurred in patients receiving five dialysis treatments each week, compared to DRT reported for the conventional approach of three weekly treatments. In addition, rapid recovery is associated with reduced mortality and fewer hospitalisations, the research indicates.

For the study, Dialyze Direct medical professionals asked patients receiving more frequent dialysis—at least 14 treatment hours each week—at their associated SNFs across 12 US states to describe their DRT following their treatments. This was done from November 2019 through June 2021.

Of the patients that met the statistical modelling inclusion criteria, 92% reported a DRT of two hours or less, and nearly 80% reported recovering in an hour or less. Lower odds of rapid DRT were observed for patients who were older, missed their previous treatment or experienced dialytic hypotension complications, while greater odds of rapid DRT were observed in patients receiving five dialyses in the previous week or having a pre-haemodialysis systolic blood pressure of 160–179mmHg.

Bluegrass Vascular announces new paper reporting use of Surfacer system

Bluegrass Vascular Technologies recently announced the publication of a paper in the Journal of Vascular Surgery that reports the use of the company’s Surfacer system to perform an ‘InsideOut’ procedure and obtain central venous access in a haemodialysis patient presenting with severely symptomatic superior vena cava (SVC) syndrome.

The procedure was performed by Alexandros Mallios (Hôpital Paris SaintJoseph, Paris, France) and his team.

“Our paper is the first to report on a fully extraanatomical, minimally invasive approach resulting in the bridging of a functioning upper-extremity access to the SVC,” said Mallios. “The use of the Surfacer system enabled us to quickly and efficiently obtain central venous access after two previous attempts to recanalise the central vein occlusion using other approaches were unsuccessful.”

This news follows an announcement from April 2022 in which Bluegrass Vascular highlighted a paper, published in the Journal of Vascular Access, that

Surfacer system

detailed the use of the Surfacer system to perform the Inside-Out procedure via a transcollateral approach. Earlier this year, the company also closed US$5

21

million in convertible debt financing to support the commercial expansion of its Surfacer system.

AlloVir reports preliminary data on posoleucel for BK viraemia in kidney transplant patients

AlloVir has announced preliminary data from an ongoing Phase 2 study of posoleucel—an investigational, allogeneic, off-the-shelf, multi-virusspecific T cell therapy for the treatment of BK viraemia in adult kidney transplant recipients. These data were shared at the 2022 American Transplant Congress (ATC; 4–8 June, Boston, USA) and provide an early indication of the safety and tolerability profile of posoleucel in this patient population.

“Kidney transplant recipients are particularly challenged by BK viraemia, which puts the survival of their transplanted graft at risk,” said Anil Chandraker (Brigham and Women’s Hospital, Boston, USA). “We currently manage high-level BK viraemia by reducing immunosuppressive therapy—which can help a patient’s immune system clear the virus—but this approach raises the risk that the immune system will attack and reject the graft.

“The potential for posoleucel to specifically restore immunity to BK viraemia as an alternative to reducing immunosuppressive therapy would be a significant advance. The preliminary safety and tolerability data from this study are highly encouraging and support the continued evaluation of posoleucel to address this important unmet need.”

AlloVir’s randomised, double-blind, placebo-controlled study is evaluating the safety and tolerability of posoleucel for the treatment of BK viraemia in 61 adult kidney transplant recipients, with the primary endpoint being safety and tolerability of posoleucel versus placebo. Topline, unblinded study results from all 61 patients are expected to be released in the first quarter of 2023, after completion of the study later this year.

New data demonstrate biomaterial-based Access Vascular catheters may improve dwell times

Access Vascular has shared initial findings from a retrospective review of patient records demonstrating an increase in dwell times compared to other commercially available devices and no complications when using the company’s consistently hydrophilic materials for midline catheters.

As a result of a three-month retrospective evaluation of 29 HydroMID midline catheters at a long-term, acute care US hospital conducted in early 2022, Access Vascular’s biomaterialbased catheters were found to have an average dwell time of 15.8 days.

Furthermore, there were no incidences of phlebitis, occlusion, deep vein thrombosis (DVT) or bloodstream infections.

The company’s patented hydrophilic catheters are composed from advanced biomaterials and mimic the body’s chemistry to reduce the most common and costly complications associated with vascular access procedures, which may meaningfully improve patient outcomes, Access Vascular claims.

Issue 4 – July 2022

22

Latest News

Industry News Medtronic and DaVita to launch new kidney health technology company

Medtronic and DaVita have together announced their intent to form a new, independent, kidney care-focused medical device company in an effort to enhance the patient treatment experience and improve overall outcomes.

According to a joint press release, the new company will be uniquely positioned to advance the development of differentiated therapies for patients with kidney failure and will focus on developing a broad suite of novel kidney care products and solutions, including future home-based products, to make different dialysis treatments more accessible to patients.

The new company will be co-owned

by Medtronic and DaVita, each with equal equity stakes, and renamed and rebranded at close. It is set to operate as an independent company and will be led by an independent management team. According to the release, the transaction is expected to close in the next calendar year.

Medtronic will contribute its renal care solutions business, including the current portfolio and pipeline of therapies, as well as global manufacturing research and development teams and facilities, but no other Medtronic products— including those in its vascular access portfolio—are included in this agreement.

US FDA grants IDE approval to MedAlliance for Selution SLR drug-eluting balloon

MedAlliance’s Selution SLR drugeluting balloon (DEB) has received investigational device exemption (IDE) approval from the US Food and Drug Administration (FDA), with the company claiming that this makes it the first limus DEB to be available to US patients.

The Selution SLR is a novel sirolimuseluting balloon that provides a controlled, sustained drug release, similar to a drug-eluting stent. Its technology involves unique microreservoirs made from biodegradable polymer intermixed with the anti-restenotic drug sirolimus.

These microreservoirs provide a controlled and sustained limus release (SLR) of the drug.

Data from the ISABELLA study, which is evaluating the treatment of dysfunctional arteriovenous accesses for dialysis with Selution SLR, were presented by Tjun Tang (Singapore General Hospital, Singapore) at the 2022 Charing Cross (CX) Symposium (26–28 April, London, UK).

Selution SLR was granted

Breakthrough Device designation by the FDA in March 2019 and further in September 2019 for below-the-knee indications in peripheral artery disease.

The device is currently available in Europe and all other countries where the CE mark is recognised.

CareDx introduces new AI-based tool for predicting kidney allograft rejection risk

CareDx recently announced that it plans to expand its growing multimodality portfolio with AiKidney—a new clinical decision support tool for renal allograft risk assessment that is in development, and includes the company’s AlloSure testing tool and other transplant metrics.

This also follows CareDx’s announcement that it plans to add an artificial intelligence (AI) prognostic for cardiac allograft vasculopathy.

Presentations covering these developments occurred during the 2022 American Transplant Congress (ATC; 4–8 June, Boston, USA).

“Studies have shown the effectiveness of CareDx’s multimodality solutions for routine kidney transplant surveillance and for identifying immunequiescence,” said Miklos Molnar (University of Utah, Salt Lake City, USA).

“AiKidney supports this assessment by providing information about a patient’s risk of allograft rejection and expected long-term graft survival. I am excited with innovations such as this one that have the potential to help prolong kidney allograft survival, which remains suboptimal at the 10-year mark.”

AiKidney delivers information about a patient’s current risk of rejection and a prognosis of allograft survival at three, five and seven years, according to CareDx, and it can be used for informing clinical management decisions and to help clinicians predict the long-term impact of treatments.

Artio closes US$28 million in additional Series A financing Artio Medical recently announced the closing of US$28 million in oversubscribed Series A2 and Series A3 financing, bringing the total amount raised by the company to date to US$74 million.

Funds will be used to support US commercialisation efforts for the recently cleared Solus Gold embolisation device and to accelerate the development of Artio’s broad portfolio of products, which also includes the Amplifi vein dilation system for enhancing successful arteriovenous fistula creation outcomes in haemodialysis patients.

According to a press release, the company will now look to grow its team, scale operations, and expand its engineering and manufacturing capabilities too.

Alio webinar unpacks challenges in end-stage kidney disease care Selution SLR balloon

July 2022 – Issue 4

Alio Medical and the Hargan Group recently hosted a webinar entitled “Bending the cost curve in end-stage

kidney disease”, covering timely topics including challenges facing the endstage kidney disease (ESKD) population and future innovation in kidney health.

The webinar took place on Tuesday 12 July, and featured David Kuraguntla, Alio co-founder and CEO, and Eric Hargan, former US Deputy Secretary of Health and Human Services.

The webinar saw discussions regarding the evolving reimbursement landscape in the USA—including how to pay for remote patient monitoring and artificial intelligence (AI) technologies, and the new role for private payers in the kidney sector.

According to Alio, this conversation represented the type of public-private partnership that will move the needle from a public policy perspective, but also attract significant investment from the start-up and venture capital community.

Outset announces shipment hold on new Tablo haemodialysis systems for home use

Outset Medical has announced that it has implemented a shipment hold on the distribution of its Tablo haemodialysis system for home use pending the US Food and Drug Administration’s (FDA) review and clearance of a 510(k) the company submitted for changes made since the device’s original March 2020 approval.

Outset claims in a press release that it has not identified any safety issues with Tablo. The company will continue to market and ship the device for use by healthcare professionals in chronic and acute care settings. Devices that are already distributed to home users have not been removed and current users can continue to work with their healthcare providers on appropriate treatment, the release details.

As a result of the shipment hold, Outset now expects second quarter 2022 revenue of at least US$25 million.

The company also anticipates an update on the status of the regulatory review process in the third quarter, and to provide an update to its 2022 revenue and other financial goals during its next quarterly update in early August. Until then, the company has suspended its prior guidance.

Hologic announces European CE marking of molecular assays for use in transplant patients

Hologic has received the European CE mark for two new molecular assays— Panther Fusion EBV Quant Assay and Panther Fusion BKV Quant Assay— expanding its transplant pathogen monitoring menu on the Panther Fusion system.

The assays quantify the viral load of the respective viruses, and are intended to aid the diagnosis and management of solid organ transplant patients and haematopoietic stem cell transplant patients. These in vitro nucleic acid amplification tests are run on the fully automated Panther Fusion system using real-time polymerase chain reaction (PCR) technology.

The Panther Fusion EBV Quant is validated for use with whole blood and plasma samples while the Panther Fusion BKV Quant is validated for use with human plasma and urine samples.

According to a company press

release, these assays represent two firsts for Hologic—they are the first quantitative assays developed for the Panther Fusion system, further expanding its existing portfolio of

Aptima and Panther Fusion assays

diagnostic and viral load tests, but they are also the first Panther Fusion assays developed at the research and development facility in Liege, Belgium, which it acquired last year.

SoniVie receives IDE approval for pilot study with renal denervation TIVUS technology

SoniVie recently announced that the US Food and Drug Administration (FDA) has granted investigational device exemption (IDE) approval for its REDUCED1 pilot study to treat resistant hypertension patients with renal artery denervation using the company’s therapeutic ultrasound ablation system (TIVUS).

The REDUCED1 study will further expand the company’s clinical experience based on two clinical trials in renal denervation performed using the earlier generation of the TIVUS. Renal denervation with TIVUS is a minimally invasive procedure that uses high-frequency, non-focused ultrasound energy to ablate nerves in the renal artery. SoniVie claims that this causes a reduction in nerve activity, which may decrease blood pressure and aid in the treatment of resistant hypertension.

Invizius awarded grant to research peritoneal dialysis indication for H-Guard technology

Invizius has announced that it has been awarded a second Biomedical Catalyst grant (Feasibility and Primer Award) by Innovate UK to research a new field of application—peritoneal dialysis (PD)— for its H-Guard technology.

The company is developing a H-Guard haemodialysis priming solution, which comprises a novel protein that lines the inside of the dialysis filter and helps dialysis to take place undetected by the body’s immune system. This suppresses the blood’s foreign body response, preventing a repetitive, hostile inflammatory reaction that increases the risk of complications.

Following receipt of this grant, Invizius will now assess in vitro and in vivo efficacy of a novel method using its technology for PD therapy before progressing into preclinical development. The project will run for 18 months and is set to assess how H-Guard technology could be applied to minimise peritoneal membrane damage.

The Biomedical Catalyst grant will allow the company to research ways of addressing this issue alongside its haemodialysis development programme—which Invizius says is “running on track” as well.

23

Events

11–14 August

10–14 September

5–7 September

10–14 September

International Society for Peritoneal Dialysis (ISPD) Congress Singapore www.ispd2022.com British Transplantation Society (BTS) Annual Congress Belfast, UK www.bts.org.uk/events-meetings/bts-annualcongress-2022

10–13 September

EDTNA/ERCA International Conference Rotterdam, The Netherlands www.edtnaerca.org/conferences/conferencesrotterdam-2022

1–3 October

International Congress of The Transplantation Society (TTS) Buenos Aires, Argentina www.tts2022.org Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Annual Congress Barcelona, Spain www.cirse.org/events/cirse-2022

29–30 September

Vascular Access Society of Britain & Ireland (VASBI) Annual Scientific Meeting Glasgow, UK www.vasbi.org.uk/vasbi-2020

Nephrology Nursing Practice, Management & Leadership Conference San Diego, USA www.annanurse.org/events/2022-nephrologynursing-practice-management-leadershipconference

31 October–3 November

Vascular InterVentional Advances (VIVA) Las Vegas, USA www.viva-foundation.org/viva-programming

3–6 November

American Society of Nephrology (ASN) Kidney Week Orlando, USA www.asn-online.org/education/kidneyweek

Meet our editorial board Nicholas Inston

Ziv Haskal

Stephen Hohmann

Robert Jones

Chairman of the Editorial Board

Board Member

Board Member

Board Member

Nicholas Inston is a transplant and vascular access surgeon, and the clinical service lead for renal surgery, at Queen Elizabeth Hospital in Birmingham, UK.

Ziv Haskal is a professor of radiology, and an interventional radiologist and interventional oncologist, at the University of Virginia School of Medicine in Charlottesville, USA.

Stephen Hohmann is a vascular and general surgeon at the Texas Vascular Associates clinic in Dallas, USA.

Robert Jones is an interventional radiologist at Queen Elizabeth Hospital in Birmingham, UK.

Issue 4 – July 2022