Renal Interventions 5 - US

Profile: John Aruny

Higher risk of allcause mortality found in female patients after starting dialysis

Compared with male patients, female patients have been found to have a higher risk of all-cause mortality in the first five years postdialysis initiation—a difference driven by higher mortality from infections and dialysis withdrawals.

THESE FINDINGS HAVE BEEN published in the American Journal of Kidney Diseases (AJKD) by Wai Lim (Sir Charles Gairdner Hospital, Perth, Australia) and colleagues.

The authors note that higher early mortality rates on dialysis have, at times, been observed among female patients compared to their male counterparts. However, discrepancies in cause-specific mortality between male and female inci dent dialysis patients are “not well under stood” and, as such, Lim et al set out to elucidate this further via a retrospective cohort study.

Their cohort included incident patients who had initiated dialysis in Australia and New Zealand from 1998–2018. The key outcomes of their analysis were cause-spe cific and all-cause mortality on dialysis. The researchers also note that they censored for kidney transplantation, and applied adjusted, cause-specific, proportional hazards models, focusing on the first five years following initiation of dialysis.

Among 53,414 patients (39% female), followed for a median period of 2.8 years, 27,137 (51%) died, with the predominant cause of death being attributed to cardi ovascular disease (CVD, 18%) followed by dialysis withdrawal (16%).

Compared to male patients, female patients were more likely to die in the first five years after dialysis initiation (adjusted hazard ratio [aHR] of 1.06). And, Lim et al report, while female patients experienced a lower risk of CVD-related mortality (aHR 0.93) compared to male patients, they experienced a greater risk of infection-re lated (aHR 1.20) and dialysis withdrawal-re lated (aHR 1.19) mortality.

After acknowledging the possibility of residual and unmeasured confounders as a potential limitation, the authors conclude that their research could help to inform the study of sex differences in mortality in other geographic settings.

Addressing “the big questions”

UK researchers alter blood type of deceased donor kidneys in “potentially game-changing” breakthrough

Researchers at the University of Cambridge (Cambridge, UK) have successfully altered the blood type of three deceased donor kidneys—a breakthrough with major implications for the future of kidney care.

This was achieved under a Kidney Research UK-funded project that, according to the researchers, could increase the supply of kidneys available for trans plant, particularly within ethnic minority groups who are less likely to be a viable match for the majority of donated kidneys.

Professor of Transplant Surgery Mike Nicholson and PhD student Serena MacMillan (both University of Cambridge) used a normothermic perfusion machine—a device that passes oxygenated blood through a human organ to better preserve it for future use—to flush blood infused with an enzyme through the deceased kidneys.

The enzyme acted like “molecular scissors” to remove the blood type mark ers that line the kidney’s blood vessels, resulting in the organ being converted to the most common O blood type. This is significant because, while an A-type donor kidney cannot be transplanted to a B-type recipient, or vice versa, kidneys from universal O-type donors can be used in patients of any group.

“Our confidence was really boosted after we applied the enzyme to a piece of human kidney tissue and saw very quickly that the antigens were removed,” said MacMillan. “After this, we knew that the process is feasible, and we just had to scale up the project to apply the enzyme to full-size human kidneys. By taking B-type human kidneys and pump ing the enzyme through the organ using our normothermic perfusion machine, we saw in a matter of just a few hours that we had converted a B-type kidney into an O type.”

This discovery could be particularly impactful for ethnic minority groups who often wait a year longer for a transplant than Caucasian patients, as per the University of Cambridge. And, in 2020/21, just over 9% of total organ donations came

from Black and minor ity ethnic donors, while these patient groups make up 33% of kidney transplant waitlists, which is thought to be a result of such populations generally being less likely to be a bloodtype match with the available supply of organs.

The Cambridge team now need to see how the newly changed O-type kidney will react to a patient’s usual blood type in their normal blood supply. The perfusion machine allows them to do this before testing in people—as they can take the newly altered O-type kidneys, use the device to introduce different blood types, and monitor how the kidney might react, simulating the process of transplantation into the body.

“One of the biggest restrictions [on] who a donated kidney can be trans planted to is the fact that you have to be blood-group compatible,” said Nichol son. “Blood-group classification is also determined via ethnicity, and ethnic minority groups are more likely to have the rarer B type. After successfully shift ing blood group to the universal O type, we now need to look at whether our methods can be successful in a clinical setting and, ultimately, carried through to transplantation.”

Kidney Research UK executive director of research Aisling McMahon described this breakthrough as “poten tially game-changing”, offering “a glimmer of hope” to the hundreds of minority ethnic groups waiting for a kidney. A full paper detailing the Cambridge team’s work is now set to be published in the British Journal of Surgery

“After successfully shifting blood group to the universal O type, we now need to look at whether our methods can be successful in a clinical setting and, ultimately, carried through to transplantation.”

O-type kidneys offer a universal transplant option

National strategies and innovations in transplantation offer positive outlook for renal patients

Research breakthroughs and newly optimised strategies have not only helped to offset the devastating impact of COVID-19, but may offer cause for genuine optimism in kidney transplantation moving forward. Nicholas Inston (Queen Elizabeth Hospital, Birmingham, UK) explains why—with a nod to several promising innovations in this space.

For patients with end-stage kidney disease, the COVID-19 pandemic has been a chal lenging time. They are a vulnerable group—based not only on health issues but more so on the logistics of regular dialysis, with an inability to socially isolate whilst attending dial ysis in units that were running close to capacity prior to the appearance of the virus. Along with the ongoing requirements for maintenance and salvage of vascular access, and other ongoing clinical needs, this has made the last two years an extreme challenge for renal patients.

The option of a kidney transplant is the hope of many dialysis patients and, while concerns regarding immunosuppression in the midst of a viral pandemic were initially raised, the cautious continuation of kidney transplantation and care ful governance, along with shared experience and data, has allowed many patients to safely receive transplants. And, representing a more promising outlook, two major documents have been released during this time.

New UK strategy

In the UK, in 2020, National Health Service Blood and Transplant (NHSBT) published its Organ Donation and Transplantation 2030 strategy—a 10-year vision supported by the four govern ments within the UK. It sets out ambitions for the UK to be a world-leader in organ donation and transplantation, building on the success of earlier strategies that saw increased living and deceased donor transplantation rates from 2013–2020.

Increased donor activity must be met with an ability to safely and effectively transplant these organs and, as such, this new strategy recognises that sustainable and resilient service develop ment will be required to enable every donated organ to be used optimally. Importantly, the allo cation of donated organs to people of diverse backgrounds and varying circumstances in a timely and equitable manner is highlighted— and partnership with charities, stakeholders, community groups and clinical teams is required to improve both donation and transplantation.

A key feature of the recommendations is an emphasis on research and innovation to not only grow transplantation, but also improve longterm outcomes. Alongside established meth ods of preservation and machine perfusion, this includes the nationally supported development

of novel technologies and techniques to optimise and possibly improve donated organs, as well as assessing organ viability, enabling the use of organs that may otherwise have been discarded.

Anthony Clarkson, director of Organ and Tissue Donation and Transplantation at NHSBT, stated “...we need to be ambitious, and set the bar high if we are going to achieve our aim of saving even more lives by designing the very best organ dona tion and transplantation service in the world”.

Alongside this, in May 2020, a legislative change to an ‘opt-out’ system of deceased donor consent was introduced in England as part of ongoing efforts to alleviate organ shortages. Under this new law, all adults in England are now considered to have agreed to be an organ donor unless they have recorded a decision not to donate or are in one of several excluded groups.

US shifts in tandem

Synchronously, the National Kidney Founda tion (NKF) has released a position paper with recommendations addressing barriers to kidney transplantation in the USA. This strategy is simi larly based on directing research to maximise the benefits of transplantation across the country by improving equity to transplantation. Whilst 22,817 Americans received a kidney transplant in 2020, there are currently more than 100,000 people on the waitlist for a kidney transplant.

Krista Lentine (Saint Louis University, St Louis, USA), lead author of the paper, noted that

“expanding opportunities for safe living dona tion, improving waitlist access and transplant readiness, maximising use of available deceased donor organs and extending graft longevity” was a priority of these recommendations. The NKF identified similar key priorities to those within the UK strategy, including expansion of living donor kidney transplantation and optimising the use of deceased donor kidneys—again, by apply ing novel technologies to preserve, resuscitate and evaluate kidneys prior to transplant.

In the USA, 20% of donated kidneys are not used for transplantation, and research to better understand the benefits versus the risks of trans planting these kidneys is essential. Directing research into novel preservation solutions and machine perfusion is suggested, as is involving both patients and clinicians in developing organ acceptance decisions, and algorithms using biomarkers and machine learning systems.

A positive outlook

After a gruelling time for renal patients, these strategies may appear to be a dove returning with an olive leaf, but perhaps they should be seen more as a phoenix rising from the ashes. Realis ing this vision of kidney transplantation will not only benefit those receiving a kidney but also allow the recovery of services needed for those patients that are not suitable for transplantation.

Home therapies like peritoneal dialysis and home haemodialysis have become more prom inent during the past two years, giving patients independence and control of their care. Further potential solutions, such as smaller portable dial ysis units and wearable artificial kidneys are in the investigative pipeline and are a focus of the US KidneyX initiative, which intends to acceler ate innovative kidney care technologies.

The pandemic has required reflection on current practices in renal replacement provision, and a great deal of learning and adaptation has occurred. For transplantation, these strategies highlight that ‘the future is not what it used to be’ and the ambition to better the lives of patients requiring renal interventions offers great hope.

Xenotransplanation—the transplant of an organ across a species barrier—has always offered hope but, whilst success (albeit short term) has been achieved, the risks are not inconsidera ble, in particular regarding cross-species viral infection. With xeno- and allotransplantation, adapting the immunological response through pharmacological means is required.

A recent breakthrough from researchers in Cambridge, UK focused on enzymatically altering the donor’s blood type rather than suppressing the recipient’s immune response. During normo thermic perfusion, blood type antigens are removed from the organ—effectively making it a universal donor equivalent to an O-type kidney, reducing barriers and potentially improving organ allocation. Such advances—and the unmet need they seek to resolve—underpin why Renal Interventions is so eager to continue reporting on the latest and greatest in kidney transplantation.

For more clinical research and policy updates from the transplant world, turn to page 8

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“After a gruelling time for renal patients, these strategies may appear to be a dove returning with an olive leaf, but perhaps they should be seen more as a phoenix rising from the ashes.”

Nicholas Inston

VASBI team signals bold new course for the society

Patient engagement, strong research collaborations, an open and inclusive canvas and year-round specialised education, will guide the multidisciplinary Vascular Access Society of Britain and Ireland (VASBI) in a new direction, says the team at the helm. Down the road, there will also be new council posts including a patient representative, patient liaison officer, and research, audit and guidelines coordinator to execute these priorities.

Robert Jones (Queen Elizabeth Hospital, Birmingham, UK), president of the society and interventional radiologist, tells Renal Interventions at a breakfast meeting: “VASBI is a truly multidisciplinary soci ety for vascular access specialists in the UK and we want our efforts and educa tion to be truly patient-focused. We know that patients who live with kidney disease are very knowledgeable and bring a unique perspective; they can be empow ered and their experience brought on board so that this is reflected along side the other care providers’ voices. Increasing engagement with patient groups is probably my highest-priority item on the agenda, followed closely by strengthening links with other societies, and offering more to the membership with specialist education courses and webinars.”

“These are all top-of-the-list items”, he says—adding sotto voce, “as is finishing this toast before the workshop begins”.

Vice president, and transplant and vascular access surgeon, Jeremy Crane (Imperial College Healthcare NHS Trust, London, UK) continues over salmon and scrambled eggs: “There has been a shift away from the ‘fistula first’ stance that was previously widely accepted. It is important to remember that patients with kidney disease are on an incredibly long journey. Whilst multiple special ists including nephrologists, surgeons, interventional radiologists, nurses and access team members will see these patients at various snapshots in time on this road, it is the patient who walks the entire distance, and we hope to equip and support them on this long lane of decision-making with up-to-date patient information.”

Mapping out the future

Following a recent council meeting, there are plans to dedicate a section of the VASBI website to patients and create accu rate, simple patient information. Jones is clear-eyed about the challenges of deliv ering this. “Trying to incorporate [the multiple options available at each point in time] into accessible, understandable patient information comprehensively is quite tricky, because it involves not just vascular access for haemodialysis but other modalities such as home dialysis and peritoneal dialysis. Cooperating with simple, accurate information about what is essentially a complex situation will be a challenge, but we are well placed to formulate this information because of the multidisciplinary fabric of VASBI,” he says.

Hiren Mistry (King’s College Hospital, London, UK), VASBI communications chair and vascular surgeon, explains: “Our aim is to develop the patient section on our website, which will be entirely issue-oriented.” And, the society is also actively increasing the emphasis on being inclusive. “We really want to reach out to the fantastic people around the country and involve all the units doing brilliant work in vascular access and bring that into the meeting,” he adds.

atmosphere should encourage people to speak up and show that all opinions matter and are heard. And we can also have a bit of banter,” she says. “The annual meeting is rather like a big multi disciplinary team being here together.”

Research collaboration is key More widely within the vascular research arena there is a ‘big tent’ approach to investigation and data collection. The Vascular Society of Great Britain and Ireland (VSGBI) has gathered a top 10 list of research priorities in vascular access (see page 6). Chief among these are: What can be done to make fistulas or grafts last as long as possible? What staff education is needed to make them understand the experience of patients living with access?

What education do patients need regard ing living with dialysis access; its impact on quality of life?

When questioned over whether this was a ‘David and Goliath-type’ situation, where the research priorities for vascu lar access were being set by other socie ties, Jones is categorical in his response.

“You can flip that around and see it as strengthening collaborations and avoid ing silos. It has nothing to do with one society’s agenda or another’s, just about forging links and working together to achieve synergistic outcomes.” This view point was echoed by Jonathan de Sique ira (University of Leeds, Leeds, UK) who presented on the priorities at VASBI 2022.

“The [Vascular Society] special interest groups aim to develop vascular access research through collaboration. There is no ownership claim on priorities or projects, and […] we encourage contact from anyone, regardless of specialty or clinical training.” The council, which also includes VASBI treasurer and inter ventional radiologist Kate Steiner (East and North Hertfordshire NHS Trust, Stevenage, UK), collectively endorses Jones’ key message that there is a unique perspective derived from being “more than the sum of all parts”, which Crane notes “does not really exist in the other meetings.”

VASBI’s strength stems from this vital multidisciplinary approach, notes Hanko. “As one of the key stakeholders in the team, to deliver dialysis, you have to be a nephrologist who is willing to be involved in vascular access, who understands it, and can relate with other members. It is absolutely critical and, year on year, we are seeing more nephrology involve ment in training.” Jones reflects that the challenge “has always been to involve interested parties, all disciplines in vascular access”. He continues: “I am very encouraged this year—the first faceto-face annual meeting in four years to see so many people from departments around the country. Following on from this, one of my aims is to try and get the smaller departments showing interest as well. Their work is often extremely valu able and we want to try and welcome and encourage them to attend a high-quality meeting right here on their doorstep in the UK.”

As Hanko concludes: “We are abso lutely clear that we will still remain friendly and interactive. I always come away from the VASBI annual meeting re-energised, armed with new informa tion and ready to take up the clinical chal lenge again, so it is a real positive flag in the calendar every year.”

“VASBI

for a certain camaraderie, [which translates to] a laidback, relaxed annual meeting that enables people who do not normally speak up to be empowered to do so.”

Crane continues: “For example, this year, the Glasgow unit talked about their multidisciplinary team approach.” He highlights that “it was one of the best sessions of the meeting”, stating: “We want them to showcase that. For many units [the VASBI annual meeting is not] on the yearly landscape. We want to change that because there is a wealth of knowl edge out there that we need to tap into.”

VASBI secretary and nephrologist

Jennifer Hanko (Belfast City Hospital, Belfast, UK) takes the view that vascu lar access work does require a friendly team that has to work well together. “The

strives

“While it is a relatively small society, [VASBI] is welcoming, friendly and includes all members of the multidisciplinary team.”

“VASBI is an organisation for everyone who has an interest in providing and improving goodquality vascular access to patients, and is completely open to all.”

Jennifer Hanko

Kate Steiner

Robert Jones

Jeremy Crane Hiren Mistry

Patient and staff education among 10 key priorities identified in vascular access research

A list of 10 key research priorities intended to help standardise vascular access research were delivered to attendees at this year’s Vascular Access Society of Britain and Ireland (VASBI) annual scientific meeting (29–30 September, Glasgow, UK). Presenter Jonathan de Siqueira (University of Leeds, Leeds, UK) stated that these priorities were devised via a “democratic and objective process” involving many different medical specialties, as well as patients, and have been made freely available for researchers to use in their own applications in an effort to overcome historic inconsistencies in UK vascular access research.

De Siqueira began by detailing the methods that shaped this ‘top 10’ priority list, which initially involved setting up a special interest group (SIG) to identify the areas that are most important to both patients and clinicians. SIGs, he reported, are subgroups of the Vascular Society for Great Britain and Ireland’s (VSGBI) central research committee, with the vascular access group being one of nine established to date.

“The first thing I want to say […] is that it is not a bunch of vascular surgeons sat in a dark room somewhere plotting how they are going to take over all research in vascular access— it is actually quite the opposite of that,” said De Siqueira. “We are a multidisciplinary team […] made up of a vascular surgeon or two, a nephrologist, a nurse specialist, a trans plant surgeon, a radiologist, and also a vascu lar scientist. And the idea is that everyone [in] this group is research focused and research orientated.”

He was keen to impress that, alongside these medical specialties, the SIG also includes a patient representative, as patient inclusion is a “core value” within the group. Discussing the motives behind creating a SIG, he noted difficulties in developing high-impact, high-level research across vascular surgery more generally, citing the lack of a “huge, dedicated funding body” like, for example, Cancer Research UK, and the “culture of competition” between different medical specialties that tends to over ride collaboration attempts. Previous grant applications have been “all over the place” depending on different physicians’ personal priorities and there has been “no consistency” to date, he asserted.

In 2019, after consulting with the James Lind Alli ance (JLA)—a non-profit making initiative focused on healthcare research—the VSGBI split into several prior ity setting partnerships (PSPs) and ultimately identified vascular access as one of nine key priorities in vascular surgery moving forward. With a SIG established, and in spite of the COVID-19 pandemic beginning to majorly impact the healthcare system across the country, paper and electronic surveys were distributed to the relevant patient groups to ascertain what is most important to vascular access patients and should therefore be prioritised.

“What was evident really early on was that access patients do not see themselves as vascu lar patients,” De Siqueira claimed. “And so, when you send a survey around [...] they think ‘that is not me’, and they do not respond.”

As such, it was signposted “very clearly” in these surveys that ‘access’ refers to dialysis access, to affirm to those patients that “we really do want to hear from them”.

Through group debates, hosted within an online priori tisation workshop, with patients and a number of medical specialties all being represented, the SIG established the following top 10 priorities in vascular access, which have since been added to the JLA website and published in the Journal of Vascular Societies Great Britain and Ireland:

1. What can be done to make fistulas or grafts last as long as possible?

2. What staff education is needed to help them to under stand the experience of patients living with a dialysis line, graft or fistula?

VASBI audience divided on optimal setting for vascular access care

A debate regarding the optimal place for vascular access creation and management to take place— specialised units or high-volume centres—saw Suresh Mathavakkannan (East and North Hertfordshire NHS Trust, Stevenage, UK) and David Kingsmore (Queen Elizabeth University Hospital Trust, Glasgow, UK) go head-to-head at this year’s Vascular Access Society of Britain and Ireland (VASBI) annual scientific meeting (29–30 September, Glasgow, UK).

ARGUING IN FAVOUR OF SPECIALIST CENTRES, Mathavakkannan began by noting the importance of multidisciplinary teams—ideally a trinity of nephrolo gists, vascular/transplant surgeons and interventional radiologists (IRs) who all have a particular interest in vascular access. He also opined that the “holy grail” is

getting 60% of all patients started on incident dialysis with a ‘definitive’ access solution rather than a tunnelled catheter. And, among prevalent dialysis patients, this target rises to 80%.

Citing the UK Renal Registry (UKRR) report, and moving onto his “biggest pitch” for special ised vascular access, the speaker said that only a handful of units reached these targets in 2019, and the majority of those that did were special ist centres—predominantly transplant centres. Here, Mathavakkannan conceded that, even in smaller-scale units, it is difficult to create and maintain a vascular access service because it is “a very resource-intensive exercise” involving a patient popu lation that has always been “very complex”, but is now getting older, frailer and more comorbid over time.

3. What education do patients need to be given about living with and looking after a dialysis line, graft or fistula and the effect this may have on their quality of life?

4. What can be done to avoid narrow segments from forming in fistulas or grafts?

5. Is a fistula always the best option for all patients who need dialysis, regardless of age?

6. What do patients need to know about the risk of having many procedures to place new fistulas, grafts and dialysis lines and the possibility of damage to the blood circulation system?

7. What features of a fistula or graft make it better or worse at providing dialysis?

8. What can be done to prevent fistulas becoming enlarged or at risk of a serious bleed?

9. What can be done to make needling of grafts and fistu las more accurate to lower the risk of problems?

10. What can be done to prevent infections related to dialysis lines?

De Siqueira acknowledged a handful of imperfections in the way the SIG arrived at these priorities, including the front end of the process being “loaded with vascu lar surgery opinion”, the inevitable obstacles raised by the pandemic, and the fact it was a fairly small group who decided on the final top 10, potentially creating an increased risk of subjectivity. However, the speaker went on to note that they arrived at a “relatively fair representation of important questions” that, crucially, was derived from a “democratic and objective process”. The individual points that came out on top were “perhaps predictably, but encouragingly, the things that scored really highly [among] patients”, he added.

Turning to what the future may hold here, De Sique ira said that—across all specialties—the National Institute for Health and Care Research (NIHR) has since set up a special funding stream specifically for projects that address a ‘JLA top 10 priority’. This means “you are not competing with everybody, you are only competing against people who can show that their project directly addresses […] a key priority”, he continued.

Moving forward, the NIHR is also prioritising ‘platform studies’ that have common outcome measures and multi ple treatment arms, and are therefore better equipped to answer questions more definitively—meaning larger, multicentre trials will likely be favoured over smaller and more disparate studies with different inclusion/exclusion criteria, outcome measures and, ultimately, conclusions.

“So, there is a real drive to establish collaborative networks for large, multicentre studies that look at multiple interven tions,” De Siqueira concluded, “and I think there is an oppor tunity to build a really formal network and prepare for some very big funding calls that can deliver high-impact research.”

However, while there is a degree of resource constraint for specialised centres, and many units need to perform more procedures and target improved outcomes to meet current demands moving forward, these challenges are even harder for high-volume centres to contend with, he continued. He further claimed this negatively impacts their ability to be both proactive and reactive in access creation, potentially increasing their numbers of unplanned starters, who will likely begin dialysis with a line.

“You need to have the ability to get it right first time, but you also need to have the ability to intervene [later], if necessary,” Mathavak kannan said. Referencing previous UK Renal Association vascular access guidelines, which emphasise the need for centres to have surgi cal and radiological intervention facilities for prompt and timely treatment of arteriovenous fistula/graft (AVF/G) stenosis, he added: “Again, that is predicated on having enough resources to do that on a daily basis—and I would argue that is only available in a specialist centre.”

Jonathan de Siqueira

Suresh Mathavakkannan

UK analysis of fistula data finds potential seven-figure cost saving with VasQ device

A cost-modelling analysis in realworld comparator groups has illustrated a potentially significant financial benefit across the UK healthcare system to using the VasQ external support device (Laminate Medical Technologies) for surgical arteriovenous fistula (AVF) creation as a standard of care compared to traditional techniques. European data supporting this—and positive clinical outcomes associated with VasQ—were presented by Robert Shahverdyan (Asklepios Klinik Barmbek, Hamburg, Germany) at the Vascular Access Society of Britain and Ireland (VASBI) annual scientific meeting (29–30 September, Glasgow, UK).

IN HIS VASBI PRESENTATION, SHAH verdyan posited that AVFs created using VasQ have demonstrated high rates of maturation, functional success (AVF being used for dialysis) and secondary patency with no apparent increase in complica tions or expense versus AVFs created via more traditional methods, in his experi ences. Shahverdyan further stated that, across multiple international studies, the device has showed a combined func tional success of 89% and a median time to cannulation of 42 days. “This is a major improvement on similar, historical surgi cal series [without VasQ] where non-mat uration and failure of functional use are as much as 50%,” he said.

In addition to this clinical benefit, AVFs created using VasQ at Shahverdyan’s centre lowered cost per patient by 21% (-€926.45) as well as cost per-success ful-access by 23% (-€1,398.07). These cost

reductions were the effect of VasQ reduc ing the need for additional maturation procedures or abandonment in favour of an alternative access option, he reported, but noted the limitations of these analyses due to their preliminary nature.

Touching on a single-centre experience from the University of Messina (Messina, Italy), Shahverdyan highlighted similar findings, with a 26% (-€1,079.46) per-pa tient cost saving and a 43% (-€2,325.48) cost per-successful-access saving. And, summarising these data and his own alongside a multicentre study from Italy and Spain, he further relayed cost reduc tions with VasQ in radiocephalic AVFs as compared to non-VasQ and snuffbox fistulas at his centre. These savings ranged from 24% (-€1,106.13) to 43% (-€2,376) between the different centres and fistula locations involved.

What do these data mean?

As Nicholas Inston (Queen Elizabeth Hospital, Birmingham, UK) told Renal Interventions, discussing the high rates of primary patency and early cannulation in Shahverdyan’s findings, and other posi tive results seen in multiple studies with VasQ to date, these data are “important” because they are based around functional success rather than surrogate markers of maturation. “In recent studies of some other devices, the access was deemed mature at an early stage—yet multiple further procedures such as angioplasties were required for it to be functional,” he stated. “The time from [fistula] creation to cannulation is the important measure here. If we have a high functional success rate, and a shorter time to successful use, the need for central venous cathe

ters [CVCs] and maturation procedures should decrease.”

According to Inston, one of the most expensive eventualities in vascular access is when a patient starts off with a fistula, which then fails to become usable for dialysis, resulting in a CVC followed by another attempted fistula creation. “You can avoid all of this if you can just get it right first time with this device,” he added. “The clinical relevance of these data is very good.”

“In terms of new devices, there have been no major advances like this in the last 50 years, since the fistula was first described,” he continued. “The endovas cular/percutaneous AVFs are a different way of doing it but the outcomes are not this order of magnitude better.” Inston also stated that the data on VasQ thus far suggest its benefits apply across the full spectrum of fistula sizes, locations and patient types—as opposed to a select group. “The data are there to say this is applicable to all patients, but further work will be needed to see if certain groups benefit more than others,” he noted.

Modelling UK impact

The clinical and economic figures deliv ered by Shahverdyan at VASBI 2022 form part of the data used by Laminate to create a national-level cost model across the UK National Health Service (NHS).

In collaboration with Myton Medtech Consulting, Laminate moved to develop a budget-impact model that would deter mine the possible financial and resource benefits to NHS England of introducing its novel external support device across the UK. Precise definitions and categori sation of patients’ AVF creation progress, and any complications experienced, were used alongside hospital episode statis tics—creating a modelled, real-world, ‘non-VasQ’ comparator group based on thousands of NHS patients.

The company then contrasted the impact of VasQ reported in previous clinical studies, derived from more than 500 patients across various global stud ies of the device, with this comparator. The results of their analysis indicated likely gains the NHS could “reasonably expect” if VasQ is adopted at hospitals, integrated care systems or nationally.

After accounting for the cost of imple menting the device, the model anticipated an overall financial saving to the NHS of £6,484,471.90 within a financial year, representing a 148% national-level return on investment, and a resource saving of 1,334 fewer procedures due to avoided complications.

Having modelled the expected NHS budget and resource impact of nation wide VasQ adoption, under the assump tion that every AVF is treated with the device, Laminate claims it has been able to “communicate a relevant, compelling value proposition” to key decision-makers in the NHS, with a controlled and trans parent adoption plan having also been developed. Inston, who assisted with this modelling, concluded that, while current VasQ data are “supportive of providing clinical benefits and having an impact on the pathway of vascular access creation”, these modelled outcomes still need to be validated in a real-world setting, with further VasQ treatments now planned in the UK and elsewhere in Europe.

Mathavakkannan concluded by reiterating that special ised centres tend to produce better patient experiences and quality, adding: “We can deliver dialysis pretty close to home, but vascular access probably needs to be done in a unit that can comprehensively manage all the service needs of the patient.”

Kingsmore’s presentation in favour of keeping vascular access ‘non-centralised’ focused on the current evidence supporting specialised/centralised care—or lack thereof. The basis of his argument centred around three key points: Firstly, the UK can be either geograph ically disadvantaged in remote rural areas or already has close access to larger centres due to high population density. Secondly, the rationale behind specialisation is well matured. “Vascular access does not meet the logical requirements for specialisation [large teams, rare conditions or technically unforgiving anastomoses in inacces sible locations],” he claimed, “and there is no evidence for it whatsoever. In fact, it may even be harmful.”

The speaker noted that the centralisation of care is “not even a modern argument”, highlighting an article

from as far back as 1945 in The Lancet that warned of “narrowness and monotony”, and limitations around “the cross-fertilisation of ideas” and collaborative work, as well as a focus on “the self-serving needs of the clini cian—rather than the needs of patients”, in the UK National Health Service (NHS).

Challenging his opponent’s assertions that specialised centres are associated with a higher level of quality, King smore said that quality of care can be broken down into the healthcare setting, its processes, and the subsequent outcomes, but pointed out the flaws in directly associating certain types of centres with certain outcomes. “Some smaller units do fantastic work, and some bigger ones—not quite so much, but it is not about the nomenclature,” he stated. “It is about the quality of care they actually deliver.” Here, he also chose to refer to the UKRR report and the fact that, in order of unit size, better outcomes were reported in terms of lower catheter use in smaller units.

And, while he corroborated Mathavakkannan’s views on the importance of a multidisciplinary team, and the

role of collaborative working, Kingsmore also reported the difficulties of achieving these ideals despite working in a large centre with all the facets required. Thirdly, and finally, he noted that the concept of centralisation is “absolutely meaningless”, as vascular access care is already centralised, and improved organisation of exist ing systems—i.e. through a multidisciplinary team-based approach—is more likely to be successful in providing more comprehensive services and overcoming issues like resource constraints at high-volume centres. “[Central isation] is impractical, it is not logical, and it may even lead to poorer outcomes,” he concluded.

In a brief discussion following the debate, both speak ers agreed that it is not necessarily the size of a given vascular access centre that matters, but rather the right level of investment and collaboration to provide a good-quality service. A straw poll of the VASBI audience, conducted by session moderator Peter Thomson (Queen Elizabeth University Hospital, Glasgow, UK), revealed a near-50/50 split in support for specialised and high-vol ume vascular access centres, leaving the issue open to further discussions.

David Kingsmore

“In terms of new devices, there have been no major advances like this in the last 50 years, since the arteriovenous fistula was first described.”

Nicholas Inston

Transplantation

New guideline supports kidney exchange programmes and “integrated approach” in sensitised patients

Writing in Transplant International, Nizam Mamode (Guy’s Hospital, London, UK), Oriol Bestard (Vall d’Hebron University Hospital, Barcelona, Spain) and colleagues focus on a handful of key areas relating to the management of kidney transplant patients with HLA antibodies, from the definition of sensitisation, and place of kidney exchange programmes (KEPs) for sensitised patients, to desensitisation strategies and outcomes after HLA-incompatible transplantation.

“Although kidney transplantation rates have increased in many countries in recent years, highly sensitised patients typically spend longer waiting for a transplant, or may never receive one,” Mamode, Bestard et al note. “This guideline is aimed at health care professionals who are faced with a patient with HLA antibodies, to provide advice regarding the most appropriate way to achieve a successful transplant.”

Key recommendations

Regarding the definition of sensitisation, the working group states that a parameter based on the HLA frequencies of the actual organ donor population—such as virtual panel reac tive antibodies (vPRA) or calculated PRA (cPRA), or calculated reaction frequency (cRF)—should be used to estimate the chance that a sensitised patient can be transplanted with a compatible donor without the need for any special treatment. They also high light the fact that no European country has a published national consensus on its opti mal recommended management pathway for highly sensitised patients, although several European centres have published protocols and outcomes following HLA-incompatible transplan tation. As such, on the topic of organ allocation, they recommend an “active policy” of prioritising highly sensitised patients for organ transplantation using cPRA/cRF with a sliding-scale score.

Discussing the place of KEPs for highly sensitised patients, Mamode, Bestard et al add that increased access to, and harmonisation of, KEPs with greater and standardised sharing of outcomes; inclusion of unspecified kidney donations (if these are performed); and inclusion of compatible pairs and deceased donor organs; should all be prioritised to increase the compat ible donor pool. “Entry into a KEP is the preferred initial option over desensitisation given the better transplant outcomes and cost-effectiveness—unless there is a need for desensitisation, clinical urgency, or a low chance of a transplant,” they continue. “The use of a KEP is preferred to desensitisation, but highly sensitised patients should not be left on a KEP list indef initely if the option of a direct incompatible transplant exists, especially when there is a very low chance of finding a compatible organ.”

The working group’s main takeaway on desensitisa tion strategies is that “the most efficacious” approach

is to start with rounds of plasma exchanges/immu noadsorption together with intravenous immuno globulin (IVIG) or B-cell depletion using anti-CD20 monoclonal antibodies. They also note that newer therapies like imlifidase may offer alternatives here, especially in the absence of living-donor transplanta tion. Mamode, Bestard et al highlight the fact that “few studies compare HLA-incompatible transplantation with remaining on the waiting list, and comparisons of morbidity or quality of life do not exist” before iden tifying several other, wider strategies, such as linking prioritisation policies across countries for equity of access, and the need for all KEPs to develop calcula tors to help assess the probability of an organ match. The working group concludes its recommendations by asserting the benefits of an integrated approach to these patients and that the aforementioned points “are not necessarily independent of each other”.

“Two points are worth emphasising— firstly, that for individual patients, the risks of the various options (including no transplant) should be assessed and conveyed using the limited data that are available,” they state. “Secondly, flexibility is important; a patient should not be left in a KSS [kidney sharing scheme] indefinitely if other options are available, or if new treatments appear.”

Future research areas

The ESOT working group also outlines multi ple areas in which more research is currently required, recommending the further stand ardisation of single antigen bead assays (for detection and quantitation of HLA antibod ies) and their interpretation. Better HLA matching on the basis of antibody epitopes—rather than antigens—and a restricted transfusion policy “will probably diminish the number of highly sensitised patients”, they add, with more data needed.

“As-yet-to-be-defined protocols, including proteas ome inhibitors and other anti-plasmocyte antibodies with costimulation blockade, B-cell immunomodula tion targeting IL-6 [interleukin 6], as well as cleavage of IgG [immunoglobin G] donor-specific antibodies [DSAs] with imlifidase, are highly promising new strat egies that deserve further investigation,” Mamode, Bestard et al continue. “We recommend that data be collected prospectively for sensitised patients [...] to compare the effect of an HLA-incompatible transplant with remaining on the waiting list. These data should include mortality, morbidity and quality of life.”

Lastly, they support the continuation of work to develop schemes that may help patients with very high cPRA or cRF who may not be transplanted in kidneypaired donations or under deceased donor priority schemes, as well as further exploration into the role of induction immunosuppression in relation to sensitisa tion and its role in long-term outcomes, and whether HLA-DSA evaluation/avoidance can improve outcomes.

American Society of Nephrology leads renewed call for US congress to protect living donors

Members of the American Society of Nephrology (ASN) and 21 organisations representing the kidney community— patients and healthcare professionals alike— recently met with their corresponding members of the US Congress to call for the protection of living organ donors by advancing the Living Donor Protection Act.

AS PER AN ASN PRESS RELEASE, WHILE a kidney transplant is the optimal and most cost-effective therapy for the majority of people with kidney failure, a national shortage of donor organs means that 13 Americans currently die every day while waiting on the nearly 100,000person kidney transplant waitlist.

Increasing living donation is important for expanding the availability of kidney transplants, according to the ASN, yet one in four organ donors report difficulty securing life, disabil ity and long-term care insurance—among other barriers—after donating an organ.

Sponsored by US representatives Jerry Nadler and Jaime Herrera Beutler, with senators Kirsten Gillibrand and Tom Cotton, the Living Donor Protection Act (HR 1255/S 377) ensures insurance companies offering life, disability and long-term care plans do not deny or limit coverage, or raise premiums based on an individual’s status as a living organ donor.

According to the ASN, the act also codifies that living organ donors can take Family and Medical Leave Act (FMLA) time to recover from donation surgery and maintain job security.

“Congress must support people with kidney diseases by removing barriers to living donors and increasing access to kidney transplanta tion,” the release states. “Advancing the Living Donor Protection Act is an important first step for increasing access to this important therapy.”

The ASN has encouraged members of the kidney community to contact their members of Congress and “urge them to take action to support living donors”.

Other kidney community organisations that have joined the ASN in this effort include the American Association of Kidney Patients (AAKP), American Nephrology Nurses Associ ation (ANNA), American Society of Diagnostic and Interventional Nephrology (ASDIN), Amer ican Society of Transplantation (AST), National Kidney Foundation (NKF), and several others.

Nizam Mamode

Oriol Bestard

A new guideline on the management of highly sensitised kidney transplant patients—those who have high levels of human leukocyte antigens (HLAs) and are therefore more likely to experience allograft rejection—has been published by a European Society for Organ Transplantation (ESOT) working group.

SGLT2 inhibitors demonstrate efficacy and safety in diabetic kidney transplant recipients

Sodium-glucose cotransporter-2 (SGLT2) inhibitors can be used safely to help preserve graft function in diabetic kidney transplant recipients, as per the findings from a retrospective cohort study published in the journal Transplantation

THE STUDY’S AUTHORS, JANG- HEE CHO (Kyungpook National University, Daegu, South Korea), Jung Pyo Lee (Seoul National University Boramae Medical Center, Seoul, South Korea) and colleagues, begin their report by noting that kidney transplant recipients are exposed to both the graft rejection and nephrotoxicity of immunosuppressants. As such, “special attention” is required to select the optimal antidiabetic medication for long-term use.

They also state that SGLT2 inhibitors have previ ously demonstrated their efficacy and safety in diabe tes patients with chronic kidney disease (CKD) through several landmark randomised controlled trials (RCTs). However, Cho, Lee et al add that no large-scale studies have been conducted to confirm these benefits and the safety of SGLT2 inhibitors in kidney transplant recipients. As such, they evaluated the impact of these medications— which are also sometimes referred to as ‘gliflozins’— in a multicentre cohort of kidney transplant patients with diabetes.

The researchers report that a total of 2,083 diabetic kidney transplant recipients were enrolled from six trans plant centres in South Korea. Among them, 226 (10.8%) patients were prescribed SGLT2 inhibitors for more than 90 days. The primary outcome of the study was a compos ite outcome of all-cause mortality, death-censored graft failure (DCGF) and serum creatinine doubling. An acute dip in estimated glomerular filtration rate (eGFR) over 10% was surveyed after SGLT2 inhibitor use too.

During the mean follow-up of 62.9 months, the SGLT2 inhibitor group had a lower risk regarding the primary composite outcome versus the control group in both multivariate and propensity score-matched models (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24–0.78; p=0.006 and adjusted hazard ratio, 0.45; 95%

Study finds creatinine-based eGFR equation could reduce racial differences in transplant waitlist times

“We believe that the findings in our study are helpful in providing som e prelim inary data on how use of the different GFR [glomerular filtration rate]-estimat ing equations would theoretically affect wait-time accrual prior to the start of dial ysis,” said first author Elaine Ku (Univer sity of California, San Francisco, USA).

Current methods primarily rely on measuring kidney function from a patient’s serum creatinine levels via their estimated GFR (eGFR). Historically, eGFR equations included an adjustment for Black versus non-Black race, result ing in higher eGFR values for Black versus non-Black patients. But—recognising that race is a social construct rather than a biological phenomenon—a joint taskforce led by the American Society of Nephrol ogy (ASN) and the US National Kidney Foundation (NKF) endorsed the removal of race modifiers from kidney function estimations by publishing a new set of race-free GFR equations last year.

EGFR is the primary criterion for determining eligibility for registra tion on the kidney transplant waitlist in patients not yet treated with dialysis—a concept dubbed ‘pre-emptive waitlist ing’. Pre-emptive wait-time accrual, or the waiting time that can accumulate before a patient starts dialysis, impacts when a patient may ultimately be offered a kidney transplant. According to current national policy in the USA, patients can begin to accrue wait time for transplantation when their eGFR is 20mL/min or less.

In their CJASN paper, Ku and colleagues report that they examined the use of two race-free 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and whether they could mini mise racial differences in accruable pre-emptive waitlist times. The team determined the association between race (Black or white) and time spent with eGFR <20mL/min per 1.73 m2 that could poten tially be accrued as pre-emptive wait time, using a new race-free, creatinine-based

Transplantation

confidence interval, 0.24–0.85; p=0.013, respectively). Cho, Lee and colleagues also detail that multivariate anal yses consistently showed a decreased risk of DCGF and serum creatinine doubling in the SGLT2 inhibitor group.

The overall eGFR remained stable without an initial dip after SGLT2 inhibitor use, the authors add. A minor ity (15.6%) of the SGLT2 inhibitor users showed an acute eGFR dip during the first month, but there was no signif icant long-term impact on the kidney function of these patients and their eGFR recovered thereafter—a finding that is consistent with prior research. Risk factors identi fied by the authors for the eGFR dip were time from trans plantation to SGLT2 inhibitor usage and mean tacrolimus trough level.

“In conclusion, this study has demonstrated that SGLT2 inhibitors have renoprotective effects and can be used safely in kidney transplant recipients with diabe tes,” Cho, Lee et al write. “Overall, the kidney transplant recipients administered with SGLT2 inhibitors showed an improvement in a composite of all-cause mortality, DCGF, or serum creatinine doubling, compared with the control group.”

The researchers also conclude that a prolonged, prospective randomised trial is now warranted, and will be needed to confirm and evaluate the potentially bene ficial effect of SGLT2 inhibitors on preserving graft func tion in diabetic kidney transplant patients.

equation, and another race-free equation that uses blood levels of cystatin C as an indicator of kidney function. Their retro spective cohort study involved chronic renal insufficiency cohort (CRIC) partici pants who were theoretically eligible for waitlist registration.

Across 472 eligible CRIC participants, the researchers found that, with the new race-free, creatinine-based equation, time to kidney failure was similar between Black and white patients, meaning poten tial pre-emptive wait times were also simi lar for Black versus white patients—with a median wait time that could be accrued of 23 months for Black patients and 22 months for white patients.

However, across 441 eligible partic ipants, the time to kidney failure for Black patients using the cystatin C-based, race-free equation was shorter, leading to a potential wait time that was 20% shorter for Black patients versus white counterparts. The median wait time that could be accrued for Black patients was 21 months compared to 26 months for white patients and, via a ’bootstrapping’ analysis method, Ku and colleagues deter mined a statistically significant difference between the time ratios of the models using the creatinine-based equation and the cystatin C-based alternative.

“We found that the new creati nine-based equation seemed to be asso ciated with a more similar wait time that could potentially be accrued compared with use of the cystatin C-based equation, but our findings require further validation in larger groups of patients,” Ku noted.

These results build on a previous study, also conducted by Ku and her colleagues, showing that Black patients had a shorter time to kidney failure (theoretically accru ing less wait time) when the older, Black race-adjusted equation was used.

“We believe that the findings in our study are helpful in providing some preliminary data on how use of the different GFR-estimating equations would theoretically affect wait-time accrual prior to the start of dialysis.”

In light of recent shifts away from race-based algorithms in medicine—such as the adjustment for Black race in equations that estimate patients’ kidney function—new research published in the Clinical Journal of the American Society of Nephrology (CJASN) has examined the impact use of these new equations could have on kidney transplant waitlist access between Black and white patients.

Jang-Hee Cho

Jung Pyo Lee

Transplantation

transplant delirium

Transplant centres “should be aware” of the cognitive risks associated with post-kidney transplant delirium and should also implement available preventative interventions to reduce delirium risk. This is the concluding message of a study published recently in the American Journal of Transplantation (AJT), which found a more-than sevenfold greater risk of dementia in kidney transplant recipients with post-transplant delirium.

The study’s authors, Mara McAdams-DeMarco (NYU Langone Health/New York University, New York, USA), Nadia Chu (Johns Hopkins University School of Medicine, Baltimore, USA) and colleagues, note at the outset that kidney transplant recipients with delirium—a preventable surgical complication—are likely to reap cognitive benefits from restored kidney function, but may be more vulnerable to longer-term neurotoxic stressors post-transplanta tion (i.e. ageing and immunosuppression).

The researchers therefore devised a prospective cohort study to further elucidate these risks. Between 2009 and 2021, they measured delirium (chart-based), global cognitive function (3MS [modified mini-mental state]), and executive function (trail making test [TMT] part B minus part A), in 894 kidney transplant recipi ents at the following timepoints:

At kidney transplantation

One, three or six months after transplantation

One year after transplantation

Annually post-transplantation

In addition, dementia was ascertained using linked Medicare claims, and the researchers repeated meas ures of cognitive performance (mixed-effects model) and quantified dementia risk (Fine-Gray competing risk model) by post-kidney transplant delirium.

Of the 894 kidney transplant recipients included in their analysis, 43 (4.8%) had post-transplant delir ium. Delirium was not associated with global cognitive function at kidney transplantation (difference of −3.2 points, 95% confidence interval [CI]: −6.7 to 0.4) or trajectories post-kidney transplantation (0.03 points/ month, 95% CI: −0.27 to 0.33), the authors note.

However, McAdams-DeMarco, Chu  et al did find that delirium was associated with a worse executive function at kidney transplantation (55.1 seconds, 95% CI: 25.6 to 84.5), greater improvements in executive function in the first two years post-transplantation (−2.73 seconds/month, 95% CI: −4.46 to −0.99), and a greater decline in executive function after two years post-transplantation (1.72 seconds/month, 95% CI: 0.22 to 3.21).

In addition, post-kidney transplant delirium was found to be associated with a more-than sevenfold greater risk of developing dementia post-transplan tation (adjusted subdistribution hazard ratio=7.84, 95% CI: 1.22 to 50.4). Based on this finding, and their results regarding executive function, the researchers conclude their AJT paper by asserting that “transplant centres should be aware of cognitive risks associated with post-KT [kidney transplant] delirium and imple ment available preventative interventions to reduce delirium risk”.

Normothermic machine perfusion may improve renal function in deceased donor kidneys

Despite not reducing rates of delayed graft function in kidneys from donation after circulatory death (DCD) donors, the novel organ storage technique of normothermic machine perfusion (NMP) has demonstrated the potential to improve renal function in DCD kidneys.

THESE ARE THE CONCLUDING FINDINGS of a randomised controlled trial (RCT) published in the British Journal of Surgery. In their report, Sarah Hosgood (University of Cambridge, Cambridge, UK) and colleagues state that this is the first trial to compare NMP to conventional cold storage in DCD kidney transplantation, and also the first RCT of NMP in clinical transplanta tion more generally.

Hosgood et al begin by noting that kidneys from DCD donors are more susceptible to cold storage injury and carry a high risk of delayed graft function. As such, they set out to directly compare NMP—a more physiological organ pres ervation technique whereby a warm perfusion solution is circulated through the kidney vascu lature to supply oxygen and nutrients—to the conventional approach of static cold storage.

In a multicentre RCT, they randomised DCD kidneys to either NMP or cold storage. The trial’s primary endpoint was delayed graft function— defined as the requirement for dialysis in the first seven days post-kidney transplant—while secondary outcome measures included renal function up to 12 months post-transplant, and patient/graft survival.

Hosgood et al state that, from February 2016 through March 2020, 338 kidneys were randomised into the trial. Twenty-five kidneys did not undergo NMP due to logistical or tech nical difficulties, but were included in an inten tion-to-treat analysis, while an additional 27 NMP-group and 21 cold storage-group kidneys were not transplanted. This led to a total of 143 NMP kidneys and 147 cold storage kidneys ulti mately being analysed.

CONCERNS REGARDING INFECTIOUS complications should not affect the imple mentation of ABO-incompatible (ABOi) kidney transplant programmes, as per the findings from a nationwide, prospective cohort study published recently in the journal Transplantation

Researchers Cédric Hirzel (Inselspital, Bern, Switzerland) et al begin their report by stating that ABOi kidney transplantation expands the kidney donor pool and may help to overcome current organ shortages—but that concerns surrounding ABOi-asso ciated infectious complications have also been raised.

In the nationwide Swiss Transplant Cohort Study, they compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) living-donor renal transplant recipients. Unad justed and adjusted competing risk regres sion models were used to compare the time to the first clinically relevant infection among ABOi and ABOc kidney transplant recipients. Hirzel et al included 757 living-donor kidney

transplant recipients—639 ABOc and 118 ABOi—and identified a total of 717 infection episodes.

“The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT [kidney transplant] and ABOc-KT recipients,” they write. “There was no significant differ ence in time to first post-transplant infection between ABOi-KT and ABOc-KT recipients. At one year, the crude infection rate was 1.11 episodes per patient-year for ABOi patients and 0.94 for ABOc-KT recipients.”

Hirzel et al therefore conclude that the burden of infections during the first year post-transplant was high, but not relevantly different between the two groups. “Our results highlight that concerns regard ing infectious complications should not affect the implementation of ABOi-KT programmes,” they add. “This is especially true for settings where administrative barriers or demographic conditions (such as small countries with low population) complicate the successful launch of paired kidney exchange programmes.”

As per the primary endpoint, there was no significant difference in the rate of delayed graft function between the NMP group (61%) and the cold storage group (58%, p=0.624). However, secondary outcome measures demonstrated a significantly higher creatinine reduction ratio day 2 (CRR2, p=0.035), and significantly lower levels of serum creatinine across all timepoints (p=0.024), with NMP versus cold storage. This led Hosgood et al to conclude that a short end period of NMP did not reduce delayed graft func tion rates in DCD kidneys but that their results as a whole suggest that NMP may improve the renal function of DCD kidneys.

Post-kidney

associated with sevenfold greater risk of dementia

Study suggests infection concerns “should not affect” implementation of ABOi kidney transplant programmes

“Transplant centres should be aware of cognitive risks associated with post-kidney transplant delirium and implement available preventative interventions to reduce delirium risk.”

Cédric

Hirzel

Renal denervation back on track with studies adding “important data to the field”

data presented by Bhatt point towards significantly greater reductions in office systolic blood pressure in patients who had undergone renal denervation versus those receiving a sham procedure at one (-18.9mmHg vs -6.3mmHg, p<0.0001), two (-24.1mmHg vs -4.3mmHg, p<0.0001) and three (-26.4mmHg vs -5.7mmHg, p<0.0001) years, while the number of antihypertensive drugs were shown to be similar between patients in each arm of the trial.

Noting that the earlier data from the trial should confer a degree of caution to the interpretation of the long-term findings, Bhatt concluded that the latest data support that durable blood pressure reductions with radiofrequency renal denervation in the presence of maximal medical therapy are “safely achievable”.

This comes on the back of a release of data from two sham-controlled renal denervation trials at the 2022 Transcatheter Cardiovascular Ther apeutics meeting (TCT; 16–19 September, Boston, USA), including primary results from the RADIANCE II trial and long-term results from the SYMPLICITY HTN-3 trial itself—described as “important data for the field” by discussants in a late-breaking clin ical science session at which the data were presented.

Ajay Kirtane (New York-Presbyterian/ Columbia University Irving Medical Center, New York, USA) presented the primary results from RADIANCE II, look ing at the blood pressure lowering efficacy of ultrasound renal denervation using the Paradise (Recor Medical) system at two months.

Through the trial, investigators from 60 study centres in eight countries screened 1,038 individuals for trial eligibility, with 224 patients with uncontrolled hyperten sion ultimately randomised 2:1 to undergo renal denervation with the Paradise system (150) or a sham procedure (74).

Patients were required to remain off antihypertensive medications through out the two months of follow-up unless specified blood pressure criteria were exceeded. At the two-month primary effi cacy endpoint, Kirtane reported, patients treated with renal denervation had a mean reduction in daytime ambulatory systolic blood pressure of -7.9mmHg, compared to a reduction of -1.8mmHg in the sham control group, corresponding to a statisti cally significant between-group difference of -6.3mmHg (p<0.0001).

Similar reductions in blood pressure were observed in night-time and 24-hour measures, as well as measurements taken at home and in the physician office. There were also no major adverse events in either group through 30 days, Kirtane reported. The trial’s primary safety endpoint will be measured at six months, and patients will be followed for a total of five years.

“The reason that we did the RADI ANCE II trial is to try and build upon prior trials such as RADIANCE HTN SOLO and TRIO which had demonstrated that renal denervation could lower blood pressure in comparison with a sham,” Kirtane commented to Renal Interventions, refer ring to earlier studies to have assessed the use of the Paradise system. “I think it pretty clearly showed that renal dener vation lowered blood pressure at two months in comparison with the sham, especially on a backdrop of patients with no medication.

“We have also shown that in a backdrop of a combination therapy with three sepa rate agents, renal denervation can lower blood pressure, and in many ways this is a confirmatory trial, but a larger trial that will hopefully lead to regulatory approval in the USA,” Kirtane said.

of adverse events, and we know that for patients that are uncontrolled that lower ing blood pressure is a good thing, I think we have seen enough examples in our field of potential questions to clinical efficacy that the onus is on us to do those kinds of trials,” Kirtane said.

Naomi Fisher (Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) offered her perspective on the trial as a specialist in hypertension, describing the condition as the “number one global burden of disease risk factor in the world”.

“We need innovation,” she commented. “Our control rates are poor and they are only falling, if you look at large statisti cal datasets showing that we are doing a worse and worse job as time goes on. We have had pharmacology around since the 1950s for high blood pressure, our last new drug class was introduced in 2007, that is how long ago that we had an innovation.

“Finally, we have evidence for an inno vative therapy that is really desperately needed to help control blood pressure.”

“I think the results that I have presented here and which were published in The Lancet are very encouraging, and I think it helps unify the field and more recent findings with renal denervation,” Bhatt told Renal Interventions, adding that the analysis complements other studies in renal denervation that have met their primary endpoints. “Viewed in that context, examining the totality of data, there is really something there,” he added.

“Renal denervation is, in fact, reducing blood pressure. It does not mean it should replace medicines or lifestyle modifica tions, but in the right patient, I think it could be a useful adjunct.”

Though the picture painted by the latest SYMPLICITY HTN-3 trial results is positive, critics have urged caution over interpre tation of the data, in particular due to the impact of the loss of benefit of randomisa tion and blinding, and potential patientand physician-related bias incurred by the crossover of patients.

A positive reception

In discussions that followed Kirtane’s presentation at TCT, speakers welcomed the findings of RADIANCE II, and their wider importance to understanding of the renal denervation as a treatment for hypertension. “We should not forget that this is the sixth sham-controlled trial that showed and confirmed the efficacy of this approach using different modalities, but also using different patient populations,” said Felix Mahfoud (Saarland University Hospital, Hamburg, Germany), who has himself been heavily involved in renal denervation research including as an investigator in the RADIANCE-HTN SOLO and TRIO trials.

Mahfoud asked Kirtane to offer his view on what for the treatment to find its way into clinical practice, to which Kirtane responded that additional safety and, importantly, clinical outcomes data will be vital. “That is important, because while blood pressure is recognised as a surrogate

Simple but effective—eventually Following on from Kirtane’s presentation, Deepak Bhatt (Brigham and Women’s Hospital Heart & Vascular Center/Harvard Medical School, Boston, USA), who delivered the long-term findings from SYMPLICITY HTN-3, acknowledged in his presentation that at six months, though renal denervation using the Symplicity (Medtronic) radiofrequency renal dener vation system had been shown to be safe, the trial’s efficacy endpoint was not met.

Bhatt shared new data from the trial, which enrolled a total of 535 patients with treatment resistant hypertension from 88 centres across the USA, all of whom were randomised 2:1 to undergo renal denerva tion (364) with an early generation of the Symplicity system or a sham procedure (171). All patients received stable, maxi mum tolerated doses of three or more antihypertensive drugs. The latest anal ysis included 101 patients from the sham control arm who crossed over to receive renal denervation after six months.

Despite the trial’s primary endpoint failure at six months, the long-term

In a comment piece accompanying the publication of the results in The Lancet, Elvira Fanelli (Université Catholique de Louvain, Brussels, Belgium) and Alexan dre Persu (AOU Città della Salute e della Scienza,

write: “Patients who had renal denervation might have received more care and attention; therefore, they might have been better managed than patients in the sham control group in terms of implementation of lifestyle modi fication, patient–physician relationship, and antihypertensive treatment. These potential biases might have different consequences: for example, they might have led to an improved adherence to antihypertensive drug treatment in the renal denervation group. In the absence of direct assessment of drug adherence, this will never be known.”

Turin, Italy),

More than eight years after results of the SYMPLICITY HTN-3 trial led the authors of a New England Journal of Medicine (NEJM) editorial to observe that the “renal denervation train” had reached a “grinding halt”, investigators have expressed renewed optimism that the procedure is back on track as a promising treatment option for hypertension.

“Finally, we have evidence for an innovative therapy that is really desperately needed to help control blood pressure.”

Naomi Fisher

Deepak Bhatt

Ajay Kirtane

John Aruny

“If I had not been an interventional radiologist, I would have been a nephrologist.” John Aruny’s abiding interest in kidney disease treatment and a long career in interventional radiology (IR) have seen him assume leading roles in the field. He was president of the Vascular Access Society of the Americas (VASA) from 2020–2022 and, until 2018, co-director of Vascular and Interventional Radiology at Yale New Haven Hospital in New Haven, USA. Speaking at the 2022 Vascular Access Society of Britain and Ireland (VASBI) annual scientific meeting (29–30 September, Glasgow, UK), Aruny—who is currently an interventional radiologist at the Dialysis Access Institute in Orangeburg, USA—tells Renal Interventions about dialysis access care being a model of multidisciplinary working; the maxims he lives by; sailing on a boat called Sonic Boom; and why he knows the names of all the Disney princesses.

ate their maturation and identify patients early on that will go on to have fistulas that do not mature? Maybe they should get grafts instead to minimise catheter contact time. Cardiologists, for instance, have a suitcase full of drugs to tackle underlying physiology. The second aspect I would look at is the venous anastomosis of the graft, or where the graft might fail and how to prevent that. So, the question really is: How can we adjust our treatment to individualise it to a particular patient when they get into trouble? The third thing is central vein stenosis—how do you prevent central vein occlusion and better treat it when it occurs?

What are the most disruptive ideas and tech nologies in dialysis access you have encoun tered in your career?

The idea that endovascular procedures could be as successful as open procedures was a major idea shift. With regard to technology, the first is the covered stent, because it changed the whole scope of practice. One, it allowed the treatment of the access to extend beyond the surgeon, and surgery, to the radiologist and the nephrolo gist. The fear was always, ‘what if I rupture the vein? I will have to call the surgeon’, and you do not have to do that anymore. Now, you have a covered stent in place across that area and basi cally take care of your own complication. It also changed the patency, certainly of the venous anastomosis in grafts, so this was definitely a disruptive technology. It remains to be seen whether drug-eluting balloons are going to be as disruptive in the dialysis space; I think we still have work to do.

As immediate past president of VASA, which of the society’s activities are you currently excited about?

Fact file

Current/recent appointments:

2018–present: Interventional radiologist, Dialysis Access Institute (Orangeburg, USA)

Up to 2018: Co-director, Vascular and Interventional Radiology, Yale University School of Medicine (New Haven, USA)

1999–2018: Diagnostic radiologist, and vascular and interventional radiologist, Yale University School of Medicine (New Haven, USA)

Education: Fellowship in Cardiovascular and Interventional Radiology, Brigham and Woman’s Hospital/ Harvard Medical School (Boston, USA)

Residency in Diagnostic Radiology, New York Medical College (Valhalla, USA)

What sparked your initial interest in medi cine, and IR?

I would probably have been a nephrologist if I had not been an interventional radiologist—there are probably very few radiologists who are inter ested in single-nephron glomerular filtration rate (GFR), or middle molecules and how they respond, but keeping up to date with develop ments in nephrology is a passion for me. It was a longstanding family friendship with a nephrolo gist, who is now one of my son’s godfathers, that got me interested in renal disease. I started out as a nuclear medicine technologist and attended a lecture about embolisation of bleeding oesoph ageal varices. That experience really impressed me; I thought: “Wow, this is something that has sort of inspired me.” I went to medical school to be an interventional radiologist after that experience.

How did you develop a programme in which IR was integral to dialysis access?

When we first developed the dialysis access programme, IR was responsible for 85% of the dialysis access service. The model was a very

simple one: we never said no. We always commu nicated well within the practice; we went to visit the dialysis centres and set up good relationships. We set up an access hotline so that they could reach us anytime. This addressed the problem that, although dialysis access units knew we were doing good work, they found it hard to book us. With this relatively simple fix we assured them we would do the booking and get the procedure done as soon as possible—usually on the same day. I had an insight into the economics of a dial ysis unit and that helped offer a service that was appreciated, and that is how the practice grew.

There was an interesting talk about identi fying research priorities in vascular access at the VASBI meeting. Did these reflect your top three priorities?

I actually took a lot of notes during the research priorities talk. The thing is, since the 1970s, we are still stretching with balloons and still push ing clot out. We really have not gotten to the underlying physiology, and I think the research questions we pursue should be: How do mature fistulas mature? What is the best way to acceler

We have talked about developing an educational video for patients. There are a lot of patients that feel that they were not offered information about the different options that were open to them; they were shunted by their nephrologists into haemodialysis or peritoneal dialysis, and maybe did not know what it was going to involve, with needle punctures, for instance. We would like to put together a professionally made video that we could distribute to nephrologists so that patients will have a background on what to expect with each of these modalities. Then, when they go in to talk to their doctor, they will have an idea of what questions to ask. Done right, I think that would be a huge contribution.

What is holding home dialysis back, in your view?

There are several obstacles, particularly in large cities where space is a constraint. If you live in a rural area, you probably have a garage or an extra room to store the cartons of fluids and bottles and all the tubing. In cities, such as Manhattan, in studio apartments, patients simply do not have the space to do so. Also, there is the social aspect of going to dialysis to consider. When patients are on haemodialysis, they sit there for hours, and they talk to each other about their problems or home life. It is almost a social club, so financial planners should consider that—the sociopsycho logical benefits of being on dialysis. There is also a real shortage of quality dialysis technicians who believe that dialysis patients will not find it hard to learn how to cannulate their own access. So, how that all translates to ‘Total Home’ remains to be seen.

Internship in Internal Medicine, Booth Memorial Medical Center/New York University (Flushing, USA)

Honours (selected): 2020–2022: VASA president

2010–2014: America’s Top Doctors, Castle Connolly

2009: Inaugural Shari Ullman Gold Medal Lecturer Award, AVIR

Principal investigator, FLEX Arteriovenous Access Registry

Illustration by: Andy Watt / NB Illustration

You make the point that vascular access is the perfect Petri dish to show the value of multidisciplinary collaboration—could you expand on this?

In the vascular access space, there is a real recog nition that ‘multidisciplinary’ is the way to go. This idea has really taken hold and maybe other groups can learn from us. To be a good interven tionist or percutaneous/endovascular special ist, you need to understand when surgery is the right option to go with for the good of the patient. While we can do a lot of things, there are some things we should not be doing; proce dures that are just not appropriate or in the best interests of the patient. There is currently a big push in IR towards interventional oncology—IR has made oncology a new frontier. I would like to make the point that you will probably save more lives doing dialysis access interventions than if you treat all the liver cancers and renal cancers you can find. So, if you are really interested in saving lives and prolonging life, then vascular access offers a great option. It can be lucrative, both financially as well as offering tremendous personal satisfaction.

Do you have a go-to phrase that you use maybe too many times at work?

I have a pretty long list of all the things that I say, but very few are shareable! One is: You know, I am a technologist, I can do what you do. Another is: Live your life knowing there is someone who wants to do your job, will do it better than you and probably for less money. So, I try to live my life along that idea.

What are your interests outside of medicine?

My wife and I have been married for 42 years and have four children. One is a chef, another an artist, our third is a businesswoman and our fourth runs a business of trivia clubs, which is why I know the names of all the Disney princesses.

I enjoy sailing and sailboat racing (on a sail boat named Sonic Boom). I also collect stamps, having inherited from my father and grandfather a collection with about 50 first-day covers, which are envelopes that are embossed with graphics or pictures of something related to the stamp that was issued. All of these people and activities keep me pretty busy.

“There is currently a big push in IR towards interventional oncology—IR has made oncology a new frontier.

I would like to make the point that you will probably save more lives doing dialysis access interventions than if you treat all the liver cancers and renal cancers you can find.”

Intraoperative vascular mapping during haemodialysis access “should be incorporated into routine practice”

Intraoperative ultrasonographic venous mapping is a useful tool to evaluate vessel suitability for arteriovenous fistula (AVF) creation, Yana Etkin (Zucker School of Medicine at Hofstra/Northwell, Lake Success, USA) concluded at this year’s Society for Vascular Surgery (SVS) Vascular Annual Meeting (VAM; 15–18 June, Boston, USA). According to the presenter, the technique may increase the rate of distal fistula creation and lower the rate of graft replacement, and therefore “should be incorporated into routine clinical practice”.

Etkin noted there is currently no consensus on how best to evalu ate the suitability of vessels for AVF creation, and preoperative sonographic vascular mapping performed by a vascular imaging facility is common despite a lack of evidence on AVF outcomes. As such, she and her colleagues attempted to eval uate the utility of intraoperative vascu lar mapping performed by the operating surgeon during access creation. They performed a single-institution, retrospective study of 239 AVFs created

in their institution between 2019 and 2021. The team only included patients who had intraoperative and preoperative vein measurements recorded. The presenter detailed that the operating surgeon performed intraoperative measurements and that the certified vascular lab carried out preoperative measurements.

Etkin noted that site selection for fistula creation was based on distal to proximal and superficial veinfirst approaches, meaning the team considered radiocephalic fistulas first followed by brachi ocephalic and then brachioba silic fistulas. Veins with a diameter of at least 2mm on intraoperative mapping were used for fistula creation.

The investigators compared intraoper ative measurements of the veins used for fistula creation to preoperative measure ments of the veins in the same anatomic location, the presenter explained. She added that the researchers reviewed the preoperative mapping and analysed which haemodialysis access would have been created if intraoperative mapping was not performed.

This advertorial is sponsored by Xeltis

The aXess vascular graft: Potentially fulfilling a major unmet clinical need in haemodialysis patients

An de Vriese (Bruges, Belgium), who is playing a leading role in an ongoing European trial investigating the aXess vascular graft, discusses the study and the significant potential held by this technology in dialysis access care.

AZ SINT-JAN BRUGGE-OOSTENDE AV (BRUGES, Belgium) is one of the implanting centres in the new AXESS European pivotal trial of aXess—a novel, restora tive, bioresorbable polymer-based vascular access graft for haemodialysis patients. Our centre had positive preliminary experience with the aXess graft, which we implanted in five patients, as part of the AXESS first-in-human (FIH) trial that recently completed enrolment. The novel structure and mechanical properties of this new device offer promise to overcome the limitations of current graft options, while over time acquiring similar proper ties to those of a native fistula. This could fulfil a major unmet need in haemodi alysis vascular access.

An unmet clinical need

According to Etkin, on average, intra operative vein measurements were about 1mm larger than preoperative vein diam eters (3.6mm vs 2.5mm), and this was consistent in all anatomic sites, includ ing the forearm cephalic vein, upper arm cephalic vein and basilic vein. Her team also found that anaesthesia type did not significantly affect intraoperative meas urements. In patients who had regional anaesthesia, the mean intraoperative vein diameter was about 3.6mm compared to 3.4mm in patients who had local anaesthesia.

When looking at preoper ative mapping alone, Etkin revealed that 71% of patients would have the same access created. In addition, 10% of patients would require a more proximal fistula created utilising superficial veins, 13% would have fistulas created using deep veins, and 6% would require a graft. In a subset of 70 patients who had a different access created based on intraoperative mapping, matura tion rates were similar, at 84%, compared to 88% observed in the rest of the cohort.

Etkin noted that there were several

limitations to the study, reiterating that this was a single-institution, retrospective study, and that only a small number of patients were included.

In the discussion following her pres entation, one audience member expressed their “surprise” that anaesthesia type did not appear to affect AVF creation in the study. “Is it perhaps sedation that causes vasodilation as opposed to the type of anaesthesia?” they asked the presenter.

“This is something we are looking at,” replied Etkin. “It might be sedation.” However, due to the small sample size of the study, she stressed that the team needs to collect data from more patients in order to carry out such an analysis. Another VAM delegate asked whether preoperative vein mapping might correlate better if it is performed well after the time of dialysis, stressing that the patients could be dehy drated when they come in for mapping.

“That is the question that is almost impos sible to answer,” the presenter posited.

“We always operate the day after dialy sis, but preoperative mapping might have been done on the day of dialysis, when the patient is dehydrated. It is very hard to tell what their fluid status is during mapping.”

There was widespread agreement with Etkin’s conclusions among the VAM audience, with one delegate likening the research to a consensus statement. This prompted the presenter to question why the guidelines do not yet endorse intra operative mapping as a standard of care.

“That is why we wanted to put these data out there, to see if there is interest in adding the recommendation of intraop erative mapping into national guidelines,” she concluded.

End-stage kidney disease (ESKD) patients requiring haemodialysis are exponentially increasing in number worldwide. The economic burden is sizeable, with costs of up to US$100,000 per haemodialysis patient annually. Current options for vascular access still entail high complication rates. Arteriovenous fistulas (AVFs) remain the preferred access for haemodialysis patients— the so-called ‘fistula-first’ treatment strategy—while arteriovenous grafts (AVGs) are generally considered a second-line approach due their inferior primary and secondary patency rates, and incidence of interventions and complications. However, the long mean time to AVF maturation (3.5 months) and the low success rate (26% at six months) led the 2019 Kidney Disease Outcomes Qual ity Initiative (KDOQI) vascular access guideline update to shift away from fistula-first, in favour of the ‘right access’ approach. Now, alternative solutions are very much in clinical demand.

The Xeltis haemodialysis access graft, aXess, is a novel, restorative, bioabsorbable implant made of electrospun supramolecular polymers. The device essentially allows the body to heal itself. Immediately after implantation, it acts as a functional haemodialysis AVG and, over time, provides a mechanical and structural scaffold for cell ingrowth propelled by the body’s natural healing process. The result is a living vessel with pluricellular components, including myofibroblasts and endothelial cells. The aXess graft enables immediate cannulation, potentially better patency rates, lower bleeding times after needle removal, and lower access site infection rates, compared to commercially available AVGs.

Assessing the aXess graft

The clinical trial evaluation of the aXess graft started with the AXESS FIH trial (NCT04898153)—a single-arm, prospective, multicentre trial assessing safety and effectiveness of the device. In this trial, 20

An de Vriese

patients were successfully enrolled in six European sites, including ours, between June 2021 and September 2022. Promising preliminary results were presented earlier this year at the Charing Cross (CX) Symposium (26–28 April, London, UK) and more recently at the Porto Vascu lar Conference (7–8 October, Porto, Portugal). Full cohort data are expected in 2023.

Following very promising early clinical outcomes, study sponsor Xeltis has now initiated the AXESS EU pivotal trial (NCT05473299) as a go-to-market multi centre trial. Primary endpoints include freedom from device-related serious adverse events and primary patency at six months. The objective is to enrol 110 patients at up to 25 European sites and follow up with them for five years. The initiation of a pivotal trial for the aXess graft is promising for the future of haemodialysis vascular access, as its core technology may potentially combine the optimum characteristics of currently avail able options to offer patients, physicians and payers a solution for a major unmet need.

References: References for this article are available online at renalinterventions.net/ xeltis-axess-eu-pivotal-trial.

An de Vriese is the head of Nephrology and Infectious Diseases at AZ Sint-Jan Brugge-Oostende AV in Bruges, Belgium, and coordinating investigator of the AXESS EU pivotal trial.

Yana Etkin

Gore and Cordis announce new acquisitions in vascular access

Recently, two major deals have been announced in the vascular access space, with Gore acquiring InnAVasc Medical and Cordis acquiring MedAlliance.

THROUGH ITS ACQUISITION OF INNAVASC, GORE will take on the company’s InnAVasc graft (IG), which was developed by Jeffrey Lawson and Shawn Gage (Duke Univer sity, Durham, USA) and is specifically designed to allow for safe, easy, reproduceable and durable access for dialysis treat ment in patients with graft circuits.

This investigational device, according to a Gore press release, is designed to protect the graft from backwall punc tures and reduce the damage associated with frequent needle sticks, which occur over the lifespan of a dialysis access, and can lead to circuit failure and shortened circuit life.

“To be stuck with two needles three times a week for haemodialysis, for 52 weeks—that is 312 times a needle goes into a patient’s graft each year,” said Stephen Hohmann (Texas Vascular Associates, Dallas, USA). “So, having a graft that has the ability to decrease risk potential and longterm injury is definitely something that would be a gamechanger.”

“Backwall punctures and damage due to exces sive needling are painful and can cause unwanted bleeding, delay or stop page of treatment, and reduced graft durability,” added Prabir Roy-Chaud hury (University of North Carolina, Chapel Hill, USA). “I greatly appreciate how this technology is intended to be so patient-centric, addressing this important interface need, for both clinicians and home caregivers.”

Having announced its acquisition of MedAlliance in Octo ber—subject to customary closing conditions, including regulatory approvals—Cordis will take over the company’s drug-eluting balloons and other vascular access technologies.

The agreement includes an initial investment of US$35 million and US$200 million payment upon closing in 2023, regulatory achievement milestones up to US$125 million and commercial milestones up to US$775 million through 2029.

Cordis will immediately begin co-promotion of MedAlliance’s Selution SLR drug-eluting balloon in markets where it is commercially available.

The Selution plat form leverages spherical MicroReservoirs made from biodegradable poly mer mixed with the drug to control the sustained release of sirolimus. The continuous manufacturing process produces millions of precisely formed, miniature drug delivery systems. According to a Cordis press release, Selution SLR is the only drug-eluting balloon using MicroReservoirs and is designed to provide the longest and most effective pharmacokinetics release profile of any device on the market.

Selution SLR received CE-mark approval for the treatment of peripheral arterial disease in February 2020 and for the treatment of coronary artery disease in May 2020. In addition, MedAlliance has obtained investigational device exemptions (IDEs) for peripheral below-the-knee and superficial femoral artery interventions, and the device’s utility in treating arte riovenous fistula stenosis is also being investigated.

“I have had the privilege to meet with clinical experts around the world and review hundreds of angiograms demon strating the impact of Selution SLR in both cardiovascular and peripheral vascular patients,” said George Adams, chief medi cal officer for Cordis. “The clinical outcomes are remarkable, to say the least—especially for patients with few, if any, other treatment options.”

KDOQI vascular access guidelines: Opportunity or concern for clinical research?

Earlier this year, in an interview with Renal Interventions, Scott Trerotola (Philadelphia, USA) remarked that “guidelines are a research workbook for the next generation”. With this statement in mind, Emma Aitken (Glasgow, UK) examines how the most recent update to the Kidney Disease Outcomes Quality Initiative (KDOQI) vascular access guidelines is likely to impact clinical research now and in the future.

The 2019 KDOQI vascular access guidelines1 provide both opportunity and concern for clinical research—opportunity to move away from the rigid era of ‘fistula first’ to one in which it is possible to challenge the longstand ing dogmas of vascular access, yet concern that ‘shared decision-making’ becomes a catch-all term to justify the lack of evidence underpinning much of our current practice.

Evidence supporting arteriovenous fistulas (AVFs) as the ‘gold-standard’ vascular access is both historic and observational. The landmark stud ies are nearly 20 years old2,3 and data from randomised controlled trials (RCTs) comparing access modalities in a contem poraneous patient cohort are lacking. There are few RCTs comparing AVFs to arteriovenous grafts (AVGs), and even fewer comparing autologous access to tunnelled central venous catheters (CVCs), yet most clinicians continue to advocate for AVF as first-line for most patients.

Breaking the mould

Rigid application of long-held clinical practice guidelines, reinforced by financial reimburse ment linked to AVF prevalence in patients on haemodialysis, has disincentivised participa tion in clinical trials—particularly trials that chal lenge the longstanding ‘fistula first’ doctrine and address the ‘big questions’ in our practice i.e. those comparing access modalities. Fixed beliefs and biases of both patients and clinicians further perpetuate this problem. Longstanding physi cian prejudices and a traditionally paternalistic approach to vascular access planning impede the expression of uncertainty where it exists. Similarly, patient advocacy groups and litera ture continue to promote autologous primacy at all costs, such that, often, by the time a patient consults their doctor, strong opinions have already formed.

Many recent RCTs aiming to compare access modalities have failed to recruit sufficient patient numbers or been halted early due to inadequate progress, at least in part because patients and/or clinicians do not perceive equipoise between the two treatment arms. The most recent, and more flexible, KDOQI vascular access guidelines have the potential to reverse this pattern by encourag ing patient choice and promoting alternate treat ment options. The ‘Life Plan’ concept also paves the way for trials of access strategy—rather than any specific access type—and allows the focus to move from access-related endpoints towards a more patient-centred approach.

Shared decision-making

Shared decision-making is a process of collabo rative deliberation in the patient-physician inter action whereby healthcare professionals inform patients about the pros and cons of the available treatment options and reach an agreement on their preferred treatment plans.4 It acknowledges the existence of reasonable alternatives (AVF,

AVG and CVC) and aims to inform patients, so that they can form and share their preferences— understanding that the issues of importance to patients (appearance, impact on day-to-day activ ities) may not necessarily mirror those of clini cians (infection, patency).

However, it is essential that efforts to advance the evidence base are not lost under the guise of ‘patient choice’. Shared decision-making is not a justification to avoid practising evidence-based medicine; rather, the opportunity to participate in clinical research should be offered as part of the shared decision-making process. Whether in pre-dialysis with excellent vessels or with a 10-year dialysis vintage having exhausted native options, it is my vision that every patient referred for vascular access crea tion would be offered the option to participate in a clinical trial. Only then will we be truly able to achieve ‘the right access, in the right patient, at the right time, for the right reasons’.

References:

1. Lok C, Huber T, Lee T et al. KDOQI Clinical Practice Guide line for Vascular Access: 2019 Update. Am J Kidney Dis. 2020; 75(4 Suppl 2): S1–S164.

2. Astor B, Eustace J, Power N et al. Type of Vascular Access and Survival among Incident Haemodialysis Patients: The Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study. J Am Soc Nephrol. 2005; 16(5): 1449–55.

3. Ravani P, Palmer S, Oliver M et al. Associations between Haemodialysis Access Type and Clinical Outcomes: A Systematic Review. J Am Soc Nephrol. 2013; 24(3): 465–73.

4. Murea M, Grey C, Lok C. Shared decision making in hemo dialysis vascular access practice. Kidney International. 2021; 100(4): 799–808.

Emma Aitken is a consultant renal transplant and vascular access surgeon at the Queen Eliza beth University Hospital in Glasgow, UK. She is currently chief investigator of the ACCess study and is also on the Renal Association’s Vascular Access Guideline Working Group.

The author declared no relevant disclosures pertaining to this article.

“Rigid application of long-held clinical practice guidelines […] has disincentivised participation in clinical trials—particularly trials that challenge the longstanding ‘fistula first’ doctrine and address the ‘big questions’ in our practice.”

Emma Aitken

Selution SLR

Amplifi vein dilation system continues to show promise following latest first-in-human study update

An update from the first-in-human study assessing the Amplifi vein dilation system (Artio Medical) was delivered by Surendra Shenoy (Washington University School of Medicine, St Louis, USA) during the first-ever latebreaking clinical trials session at this year’s Venous Endovascular Interventional Strategies (VEINS) conference (30–31 October, Las Vegas, USA).

“It is probably the most exciting thing to have happened in vascu lar access since the description of the arteriovenous fistula [AVF] for the first time in 1966,” Shenoy noted during his presentation. “It is poised to make a huge impact for our patients.”

The Amplifi vein dilation system has been designed to overcome the age-old problem of AVF non-maturation in the forearm. While native fistulas are still widely considered the optimal, initial vascular access strategy in the majority of patients—particularly ones created at the forearm, due to reduced complication rates and the fact they preserve proximal sites for future accesses—these anastomo ses are often associated with a high likeli hood of maturation failure.

In addition, small vein diameters are strongly correlated with maturation fail ure. An Artio press release details that 6mm veins have a 75% probability of maturation versus just 10% for 3mm veins. As such, the Amplifi device, comprised of a wearable pump and catheters, is intended to improve AVF maturation rates by instigating vein dilation prior to crea tion of a fistula. This is achieved by deliv ering non-pulsatile, supraphysiologic wall shear stresses within the patient’s target vein to stimulate flow-mediated dilation.

In the prospective, non-randomised, single-arm, open-label, first-in-human study determining the safety and effec tiveness of the Amplifi system, an initial cohort of five end-stage kidney disease (ESKD) patients were treated at Sanatorio

Italiano (Asunción, Paraguay) between the first and third quarters of 2021. Posi tive results from these early investiga tions, including forearm and upper-arm mean cephalic vein diameters more than doubling across a mean treatment dura tion of 8.6 days, were also disclosed by Shenoy himself at last year’s Vascular InterVentional Advances (VIVA) confer ence (4–7 October 2021, Las Vegas, USA).

At VEINS 2022, Shenoy delivered data on a second groups of patients treated through the third quarter of this year in the first-in-human trial, reporting a mean treatment duration of 6.3 days, and noting that all AVFs in this most recent cohort were created in the forearm. The speaker further stated that no serious device-related or procedural adverse events were seen here. Treatment with the Amplifi system resulted in a 151% increase in cephalic vein diameter, with a 134% concomitant increase in flow rate, he added, and AVFs made with Ampli fi-treated veins were fully mature within two weeks and all patients were cleared for haemodialysis using their AVFs by week six.

The Amplifi vein dilation system is currently in development and there fore not available for commercial use, according to Shenoy, and further data bolstering these promising early signals are required—with a US Food and Drug Administration (FDA)-approved investi gational device exemption (IDE) trial of the device now planned and set to begin enrolment in 2023.

EVA DROP study to assess blood pressure changes and cardiac output after endoAVF creation

At this year’s EndoVascular Access (EVA; 24–25 June, Patras, Greece) meeting, the design and intentions of the EVA DROP study—which will seek to evaluate blood pressure changes associated with device-created arteriovenous fistulas (AVFs) for haemodialysis—were presented by Georgia Georgopoulou (University Hospital of Patras, Greece).

AT THE OUTSET OF HER PRESENTATION, Georgopoulou said previous studies have indi cated that surgically created AVFs lower blood pressure by decreasing peripheral resistance, but also lead to renin-angiotensin-aldosterone system (RAAS) activation and stimulation of the sympathetic system, increasing cardiac output and causing left ventricular hypertrophy (LVH).

Georgia Georgopoulou

As such, the EVA DROP study was set up to evaluate possi ble decreases in blood pressure following minimally inva sive AVF creation with the WavelinQ system (BD)—as well as assessing potential early effects on other factors like cardiac output and arrhythmias. This prospective, single-centre, single-arm proof-of-concept study intends to enrol 20 pre-di alysis chronic kidney disease (CKD) patients. Georgopoulou noted that the study represents a multidisciplinary team effort, with investigators spanning interventional radiology, nephrology and cardiology departments, including principal investigator Panagiotis Kitrou (University Hospital of Patras, Greece). Among the key aspects of the trial’s inclusion crite ria, Georgopoulou continued, is the fact that all patients have established, non-reversible kidney failure and are set to start haemodialysis within six months of recruitment in EVA DROP.

“Our primary endpoints are blood pressure changes [defined as the level of mean blood pressure change] and the possible impact of endoAVF creation to the increased output,” she said, “while secondary endpoints are the arrhythmic risk profile and the evaluation of possible independent factors that may influence our primary endpoints.”

She went on to report that the investigators will record 24-hour blood pressure measurements in the contralateral arm intended to undergo endoAVF creation, adding: “We will collect several blood pressure datapoints with a very sophis ticated blood pressure-measurement device.” These various datapoints range from peripheral and central aortic blood pressure, to augmentation index (AIx) and pressure, to pulse wave velocity (PWV) and ‘arterial stiffness’. Georgopoulou noted that a number of cardiac rhythm measurements are also set to be monitored over a 24-hour period in the study, and patients will undergo an echocardiogram and, “as we are talking about vascular access”, flow and vessel diameter measurements will be examined both before AVF creation and at follow-up, as well. The speaker noted three key timepoints for these assessments: prior to AVF creation; six weeks after AVF creation; and at a third timepoint dependent on whether or not the fistula has matured (two months if non-matured), and also whether it will ultimately be required for dialysis.

Speaking to Renal Interventions , principal investigator Kitrou said: “This is a proof-of-concept study with a small number of patients and a short follow-up. However, we believe that this is a good step forward and will help us to better understand the systemic blood pressure and cardiovascular changes following percutaneous fistula creation. It is important to explore the clinical impact these percutane ous fistulas have, with the aim to improve the service provided to our patients.”

“It is important to explore the clinical impact these percutaneous fistulas have, with the aim to improve the service provided to our patients.”

Panagiotis Kitrou

Panagiotis Kitrou

“It is probably the most exciting thing to have happened in vascular access since the description of the arteriovenous fistula for the first time in 1966.”

Surendra Shenoy

Registry data highlight longterm trends in haemodialysis access profile of failed kidney transplant patients

New findings, recently published in the Journal of Vascular Access (JVA), provide insight into the haemodialysis access profile of failed kidney transplant patients treated in the Catalonia region of Spain over an 18-year period.

Researchers Ramon Roca-Tey (Hospi tal Universitari Mollet, Barcelona, Spain) and colleagues note that data on vascular access use in failed kidney transplant patients returning to haemodialysis are limited. In the present study, therefore, the investigators sought to analyse the vascular access profile of this patient group, the factors associated with the likelihood of haemodialysis reinitiation through an arteriovenous fistula (AVF), and the effect of vascular access in use at the time of kidney trans plant on kidney graft outcomes.

In their report, Roca-Tey  et al  write that they examined data from the Catalan Renal Registry on failed kidney transplant patients restarting haemodialysis and incidence haemo dialysis patients with native kidney failure over the period from 1998–2016.

The authors report in  JVA that the vascular access profile of 675 failed kidney transplant patients at haemodialysis reinitiation compared with that before kidney transplant and with 16,731 incident patients starting haemodialysis was 79.3% vs 88.6% and 46.2% (p=0.001 and p<0.001) for AVF, 4.4% vs 2.6% and 1.1% (p=0.08 and p<0.001) for arteriovenous graft (AVG), 12.4% vs 5.5% and 18% (p=0.001 and p<0.001) for tunnelled central catheter and 3.9% vs 3.3% and 34.7% (p=0.56 and p<0.001) for non-tunnelled catheter.

In addition, they reveal that the likelihood of

haemodialysis reinitiation by AVF was signifi cantly lower in patients with cardiovascular disease, a kidney transplant duration of more than five years, those dialysed through AVG or tunnelled central catheter before kidney trans plant, and those of the female sex.

The authors add that analysis of Kaplan-Meier curves showed a greater kidney graft survival in patients dialysed through arteriovenous access than in patients using catheters just before kidney transplantation. Finally, Cox regression analysis showed that patients on haemodialy sis through arteriovenous access at the time of kidney transplantation had lower probability of kidney graft loss compared to those with cathe ters, Roca-Tey and colleagues write.

The authors conclude that the vascular access profile of failed kidney transplant patients return

“To reduce the proportion of failed kidney transplant patients returning to haemodialysis with a central line, better vascular access management is needed.”

ing to haemodialysis and incident patients start ing haemodialysis was different. They also note that, compared to before a kidney transplant, the proportion of failed kidney transplant patients restarting haemodialysis with an AVF decreased significantly at the expense of a tunnelled central catheter, and that patients on haemodialysis through arteriovenous access at the time of a kidney transplant showed greater kidney graft survival compared with those using a catheter.

According to the researchers, there are two clinical implications that can be derived from their findings. “To reduce the proportion of failed kidney transplant patients returning to haemodialysis with a central line, better vascu lar access management is needed,” they state, outlining the first implication. The second implication, Roca-Tey et al  believe, arises from the impact of arteriovenous access on kidney graft outcomes. They elaborate: “If our results are confirmed in further studies, including a larger number of kidney transplant patients and not simply patients returning to haemodialysis, routine arteriovenous access closure after a successful kidney transplantation should not be performed.”

In the discussion of their findings, the authors state that a number of factors limit the strength of their findings. They highlight the use of a popu lation registry database for this study as a key weakness, for example. “The variables used are restricted in number and can have low clinical specificity,” they note, giving the example that the number of litigated accesses, as well as those with spontaneous thrombosis and not salvaged, were not recorded.

Furthermore, the researchers acknowledge a weakness pertaining to the effect of vascular access on kidney graft survival—a secondary aim of the study. They elaborate: “Kidney trans plant patients who returned to haemodialysis were considered instead of all kidney transplant patients, and this may be a bias in our study.”

Despite these drawbacks, Roca-Tey and colleagues close their report by underscoring some key strengths of their research, referencing in particular its sample size and the prolonged duration of the study period, which they describe as “a sufficient number and time to make valua ble conclusions”.

Arteriovenous graft use linked to venous thromboembolism risk in haemodialysis patients

In an observational cohort study of Medicare beneficiaries receiving haemodialysis, the use of an arteriovenous graft (AVG) compared with an arteriovenous fistula (AVF) was associated with an increased risk of deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Conversely, researchers also found that there was littleto-no difference according to the access type in the rates of major bleeding or other cardiovascular outcomes. These results were recently published in Kidney Medicine.

IN THEIR REPORT, AUTHORS

Nicholas Roetker (Hennepin Healthcare Research Institute, Minneapolis, USA) and colleagues write that the risks of major bleeding, thrombosis and cardio vascular events are elevated in patients receiving maintenance haemodialysis. The team’s objective was to compare the risk of these outcomes in haemodialy sis patients according to the permanent vascular access type.

Using data from the United States Renal Data System (2010–2015), the research ers included in their study patients with kidney failure who were more than 18 years old, had Medicare as the primary payer, were not using an oral anticoag ulant, and were newly using an arterio venous access for haemodialysis.

Roetker et al compared 17,763 AVG and

60,329 AVF users, estimating the threeyear incidence rates and incidence rate ratios (IRRs) of various outcomes, specif ically major bleeding, venous throm boembolism (VTE), ischaemic stroke, myocardial infarction, cardiovascular death, and chronic limb-threatening ischaemia.

In Kidney Medicine, the authors report

that the use of an AVG, compared with that of an AVF, was associated with an increased risk of VTE (10.8 vs 5.3 events per 100 person-years; adjusted IRR, 1.74; 95% confidence interval [CI], 1.63–1.85) but not with the risk of major bleeding (IRR, 1.04; 95% CI, 0.93–1.17). They add that the use of an AVG was also potentially associated with a slightly increased risk of cardiovascular

death (IRR, 1.09; 95% CI, 1.01–1.16).

The investigators acknowledge some limitations of their study, noting for exam ple that the analysis included only patients with a functioning access, and that the scope of outcomes considered provides an “incomplete picture” of the risks facing access users.

“While this analysis was primar ily concerned with assessing bleeding, thrombotic and cardiovascular events, the risk of a variety of other serious clini cal outcomes should be considered when choosing a vascular access,” they write.

Furthermore, the authors note that their study included Medicare fee-for-service beneficiaries with Part D coverage who were not receiving oral anticoagulation; as such, they comment that “the results may not be generalisable to other kidney failure populations”.

In their conclusion, Roetker and colleagues summarise that the use of an AVG, relative to an AVF, in haemodialy sis is associated with an increased risk of VTE. They remark on the implications of these findings: “Given recent guidelines emphasising selection of the ‘right access’ for the ‘right patient’, the results of this study should potentially be considered as one additional factor when selecting the optimal access for haemodialysis.”

Ramon Roca-Tey

Phase 2 trial demonstrates potential of medication-free treatment for metastatic kidney cancer

BUILDING UPON “PIONEERING WORK” at University of Texas Southwestern (UTSW) Medical Center (Dallas, USA), investigators recently reported the results of a clinical trial exploring the role of stereotactic ablative radia tion therapy (SAbR) for patients with a handful of metastases, or so-called oligometastatic disease. As per a UTSW press release, this represents the first clinical trial for patients with untreated oligometastatic kidney cancer.

“There has never been a clinical trial for these patients. It is unclear whether these patients should be treated with medication, surgery, or another approach. This represents an unmet medical need,” said Raquibul Hannan, lead author of the study along with Robert Timmer man and James Brugarolas (all UTSW).

As per the release, metastatic kidney cancer is typically treated with immunotherapy agents or targeted drugs, which are toxic and dimin ish quality of life. For most patients, the disease ultimately progresses, necessitating a change in treatment, until patients exhaust their options. Most metastatic patients eventually succumb to the disease, with these drugs negatively impact ing the quality of their remaining lifespan.

The Phase 2 clinical trial tested SAbR, a treat ment that delivers potent, narrow beams of radi ation to tumours, in 23 kidney cancer patients with oligometastases (up to five metastases) at UTSW and the affiliated county hospital, Park land Health. Patients received SAbR to meta static tumours at the outset and while the disease remained oligometastatic. Overall, 57 metastases were treated. The primary goal was to control the metastatic cancer in at least 60% of patients at one year.

The study was successful, with more than 90% of patients demonstrating disease control at one year without systemic therapy. “It appears that most patients will be free of systemic therapy for at least two years,” said Hannan. None of the patients experienced serious side-effects either, the release notes, and periodic questionnaires showed no negative impact on quality of life. A large, Phase 3 randomised clinical trial evaluat ing SAbR for oligometastatic kidney cancer has now been approved by the National Cancer Insti tute and will also be led by Hannan.

“If successful, this Phase 3 trial will establish, for the first time, a standard of care for patients with oligometastatic kidney cancer,” added Brugarolas. “The hope is that the treatment will help patients by delaying progression while preserving their quality of life.”

Effective alternatives to surgery for renal cell carcinomas discussed at CIRSE 2022

The first of four presentations was delivered by Rosario Grasso (Campus Biomedico University Hospital Foundation, Rome, Italy), who argued that percutaneous thermal ablation approaches like radiofrequency ablation (RFA) or cryoablation are an option for the management of patients with clini cal-stage T1 renal lesions—primarily in masses <3cm in size, but potentially for larger masses in select patients too.

Grasso stated a belief that percutaneous ablation represents a safe and effective alternative to surgery in treating T1a renal cell carcinomas due to the “excellent” functional and techni cal outcomes seen with the procedure. The “very low” complication rate these procedures hold also compares favour ably to those associated with nephrec tomy, he added.

The speaker concluded that there is currently Level C evidence that, in selected patients with suspected T1a renal cell carcinoma, percutaneous thermal ablation should be offered over active surveillance owing to the “accept able” long-term oncological and survival outcomes it has demonstrated to date.

Grasso also said RFA, cryoablation and microwave ablation are all appropriate treatment modalities, and claimed that the choice of ablation method “should be left to the discretion of the operating physician”.

Treatment planning

Arian van Erkel (Leiden University Medi cal Center, Leiden, The Netherlands) followed this by discussing treatment planning in renal ablation—a “well-estab lished” treatment for small T1a tumours.

He posited that the first step here is to choose between surgery, ablation or active surveillance, and that this deci sion is an individualised one influenced by patient preference, age and life expec tancy, renal function, the location and size of the tumour, and multiple other factors.

“Planning the treatment of your RFA is very important in getting complete ablation, with a sufficient margin, and in avoiding complications,” van Erkel asserted. “This planning involves image guidance, the ablation modality and protective measures.” He further claimed that axial diameter, bowel proximity, adjacency to the ureter, and several other characteristics of the tumour, should be taken into account.

“An immediate CT [computed tomography] after ablation is, of course, important, to evaluate your complications and your ablation margins especially,” van Erkel concluded. “And, there is software on the market that can help you make these estimations in a more scientific and exact way.”

Different modalities

A closer look at the different approaches to percutane ous ablation for renal cell carcinoma was then provided

by Esther Gálvez González (Hospital Severo Ochoa, Madrid, Spain). The speaker corroborated many of her colleagues’ earlier points, noting that ablative treat ment is as effective as surgery in T1a tumours—adding that it can also help to preserve renal function, and is associated with low complication rates.

Gálvez González further asserted that a key advan tage held by RFA is the wealth of experience and high volume of published papers associated with the tech nique, but also noted two important limitations: ther mal tissue conductivity and the ‘heat sink effect’. In contrast, she continued, bigger tumours can be ablated more quickly, and at higher temperatures, with microwave ablation, while its relative insensitivity to the heat sink effect allows it to be used in target areas located closer to larger blood vessels. The major limitation of micro wave ablation, however, is the increased risk of complications in more central loca tions, which restricts its use to peripheral lesions, she added.

The speaker also touched on the vari ous advantages and limitations of two other approaches—cryoablation, and a non-thermal technique (on which there are minimal published data) called irre versible electroporation—stating that both are essentially unaffected by impedance and the heat sink effect, but are limited by smaller ablation volumes and longer procedure times as well. Gálvez González concluded by asserting the importance of selecting the correct approach based primarily on the size and location of the target tumour.

Combined therapies

The session’s final talk was given by Marco van Strijen (St Antonius Hospital, Nieu wegein, The Netherlands), who outlined several combined treatments in cryoabla tion. “Combined treatment in renal cryo ablation, in my opinion, consists of either embolisation—which is a safe treatment but for which scarce literature is availa ble—or thermoprotection by liquid; air or CO2 dissection; or pyeloperfusion,” he stated. Homing in on the former tech nique, the speaker said that, despite the limitations around previous studies and a lack of prospective data, percutaneous embolisation is considered a safe proce dure that is “most effective” in reducing periprocedural blood loss, and holds potential benefits in local tumour control and procedural visibility.

Van Strijen went on to highlight two further, more recently introduced tools that he also considers among the options for combined approaches: robotic needle placement, and the use of integrated controls and augmented reality to perform ablations virtually with the aid of a HoloLens device (Microsoft). In concluding his presentation, van Strijen added: “Robotic needle placement is currently one of my favourite techniques.” Here, he cited the fact it is “very simple”, and enables steep angulations, as well as reducing radiation expo sure and speeding up the procedure “considerably”.

The management of renal cancer patients featured prominently at this year’s Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual meeting (10–14 September, Barcelona, Spain), with discussions around patient selection and treatment planning preceding talks on the key therapeutic options in this space.

“There has never been a clinical trial for these patients. It is unclear whether [they] should be treated with medication, surgery, or another approach. This represents an unmet medical need.”

Raquibul Hannan

Arian van Erkel

Esther Gálvez González

Rosario Grasso

Marco van Strijen

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Renal community reckons with removal of race variable in kidney disease diagnosis

Vascular Therapies initiates enrolment in ACCESS 2 clinical trial

Vascular Therapies has announced that the first patient in the ACCESS 2 clinical trial has been enrolled by Nikhil Kansal at Harbor-University of California Los Angeles (UCLA) Medical Center in Torrance, USA.

The Phase 3, prospective, randomised ACCESS 2 study will enrol 120 patients from centres in the USA and UK. It is being conducted to validate what Vascular Therapies describes as an “encouraging” subgroup analysis from the first Phase 3 (ACCESS) study, which showed that the use of Sirogen—a proprietary sirolimus formulation—in end-stage kidney disease patients aged 65 years and older resulted in clinically meaningful improvement in arteriovenous fistula (AVF) maturation and durability.

“We are excited to participate in this randomised clinical trial that addresses an important unmet clinical need,” Kansal commented. “The elderly population is the fastest growing segment of the haemodialysis population and these patients urgently need a solution to improve AVF maturation.”

In a press release, Vascular Therapies advises that the Sirogen drug development programme has received fast-track status from the US Food and Drug Administration (FDA).

clinical trial in the throes of the COVID-19 pandemic, we are thrilled to observe these positive results of RADIANCE II—especially in light of those we have previously reported from RADIANCEHTN SOLO and TRIO,” said study principal investigators Ajay Kirtane (New York-Presbyterian/Columbia University Irving Medical Center, New York, USA) and Michel Azizi (Hôpital Européen Georges Pompidou, Paris, France). “We cannot adequately convey our thanks to the patients, coordinators and study physicians for their collective efforts, and we very much look forward to being able to present and publish the complete study details in the near future.”

RADIANCE II is the third and largest component of ReCor’s RADIANCE global programme, which comprises multiple randomised and shamcontrolled studies evaluating the Paradise ultrasound RDN system in patients with hypertension. The first two studies in the series, RADIANCE-HTN SOLO and TRIO, both met their primary effectiveness endpoints.

Natera announces enrolment completion for RenaCARE study

Natera has announced full enrolment for the RenaCARE study—a real-world, prospective, multicentre trial to assess the clinical utility of the company’s Renasight genetic testing panel, which analyses more than 380 genes related to kidney disease.

Enrolment in the study was completed early as a result of statistically meaningful interim data analysis, according to Natera. It includes more than 1,700 patients across 30-plus sites, representing leading academic and private nephrology clinics in the USA, with a publication for the RenaCARE study now expected to be submitted in early 2023.

study—a first-in-human clinical trial of its restorative haemodialysis access graft, Axess.

The company has also reported that enrolment in the trial is now complete, with 20 patients having been successfully implanted with the synthetic, bio-restorative vessel graft.

During haemodialysis, the Axess device demonstrated 100% cumulative primary and secondary patency rates, with an average follow-up time of 5.8 months and no device-related complications, in patients implanted by Matteo Tozzi and his team at the University of Insubria (Varese, Italy)— one of six European sites participating in the trial.

These data were presented recently at the Porto Vascular Conference (PVC; 7–8 October, Porto, Portugal). To date, Axess has enabled more than 1,200 haemodialysis sessions in just over a year as part of the AXESS first-inhuman trial, with 60 of these sessions taking place in Varese.

“Our initial clinical experience with Axess is very promising, from implanting to puncturing, and the data on functionality observed so far are very encouraging,” Tozzi commented.

Fluidx announces successful enrolment of final patient in liquid embolic multicentre trial Fluidx Medical has announced completion of trial enrolment for its GPX embolic device. In this multicentre trial, GPX was used to treat a variety of primary and metastatic tumours, and renal adenoma tumours, and in a range of other arterial and venous applications.

it will be an exciting addition to the embolic portfolio for interventionists.”

Talaris announces positive kidney graft acceptance findings from FREEDOM-1 study

Talaris Therapeutics recently provided a clinical update on its ongoing Phase 3 FREEDOM-1 study of FCR001—the company’s investigational allogeneic cell therapy designed to induce immune tolerance to a kidney graft in living donor kidney transplant recipients.

To date, Talaris has enrolled 22 donorrecipient pairs and seven patients have been successfully dosed at five different trial sites in the study. According to the company, all three patients who were dosed more than 12 months prior to the data cut-off date have been successfully weaned off all chronic anti-rejection drugs without evidence of rejection and with stable kidney function. All of these patients, including the first patient—who is now 24 months post-transplant—continue to remain off all anti-rejection drugs.

The safety profile observed was generally consistent with that expected in patients receiving a kidney transplant and an allo-haematopoietic stem cell transplant (HSCT), a Talaris press release states. Three cases of low-grade acute graft-versus-host disease (aGvHD) were reported, all of which were treatment-responsive and have since resolved. Trial enrolment continues, the release adds.

ReCor Medical and Otsuka Medical Devices have announced that the RADIANCE II US Food and Drug Administration (FDA) investigational device exemption (IDE) pivotal trial evaluating the Paradise ultrasound renal denervation (RDN) system as a treatment for hypertension has met its primary efficacy endpoint, demonstrating a statistically significant reduction in daytime ambulatory systolic blood pressure between treatment and a sham procedure measured at two months.

The RADIANCE II US FDA IDE pivotal trial is a randomised, shamcontrolled clinical trial of the ReCor Paradise ultrasound RDN system for the treatment of patients with uncontrolled hypertension. Some 224 patients with mild-to-moderate uncontrolled hypertension, previously treated with up to two medications, were randomised while off medications at more than 60 study centres in eight countries.

“Despite the truly formidable challenges of conducting a complex

The study aims to demonstrate how genetic findings impact the clinical management of patient care and examines outcomes of patients tested with the Renasight genetic testing panel. It will also assess patient satisfaction, health knowledge and genetic literacy.

“Chronic kidney disease [CKD] affects more than 10% of the global population, and our 2019 NEJM [New England Journal of Medicine] study showed roughly a 10% genetic yield among CKD patients,” said Ali Gharavi (New York-Presbyterian/Columbia University Irving Medical Center, New York, USA), the study’s principal investigator, following the launch of RenaCARE earlier this year. “We are optimistic that this study will show that next-generation sequencing multi-gene assays can be used in a real-world setting, to inform and guide disease management, and help improve patient outcomes.”

“We are pleased to announce the enrolment of the final patient in the trial and look forward to participating in future trials using this promising technology,” stated the trial’s principal investigator, Andrew Holden (Auckland City Hospital, Auckland, New Zealand). “In the trial, GPX showed significant potential to advance liquid embolics, penetrating very distally, providing profound embolisation, and demonstrating excellent radiopacity, which helped to avoid non-target embolisation and preserve healthy adjacent tissue.”

GPX has shown promising results for tumour embolisation and other uses where there is a desire for distal vessel bed penetration, a Fluidx press release details.

Interim results of the GPX study have been presented at multiple congresses this year, including the Global Embolization Symposium and Technologies (GEST; 19–22 May, New York, USA), the Leipzig Interventional Course (LINC; 6–9 June, Leipzig, Germany), and the Society of Interventional Radiology (SIR) annual scientific meeting (11–16 June, Boston, USA).

Earlier this year, Talaris also announced the presentation of additional Phase 2 data and analyses involving its facilitated allo-HSCT therapy platform at the 2022 American Transplant Congress (ATC; 4–8 June, Boston, USA). In a separate release, the company stated that real-world, retrospective analyses of Phase 2 patients versus matched controls found improved kidney function and fewer cardiometabolic complications in FCR001-treated patients, as compared to those on immunosuppression, after five years.

VentureMed announces first patient treatment with 75cm-length Flex vessel prep product

VentureMed Group has announced that Ari Kramer (Spartanburg Regional Healthcare System, Spartanburg, USA) has treated the first patient with a new, 75cm-length iteration of its Flex vessel prep system.

“The Flex vessel prep system offers a unique, non-balloon-based prep that extends patency between interventions and decreases the need for stenting,” said Kramer. “This new 75cm device is especially beneficial for me to reach and treat the very challenging cephalic arch

Xeltis has announced what it describes as “very promising” preliminary efficacy and safety results from one of the centres participating in the AXESS

“We have only touched on some of the applications,” Holden concluded. “Further trials will provide opportunities to look at broader applications of this product. We believe

This first treatment was part of VentureMed’s successful limited market release of the new 75cm product, which was created to address often hard-toreach and problematic lesions in the cephalic arch region, and will be available in Q4 2022, according to the company.

ReCor announces renal denervation has met primary efficacy endpoint in RADIANCE II study

Xeltis presents “promising” first-in-human data on restorative haemodialysis access graft

Paradise system

Andrew Holden

Transit Scientific announces US FDA clearance for XO RX angioplasty platform

Transit Scientific has announced that the XO RX 2.2Fr and XO RX 3.8Fr platform has received US Food and Drug Administration (FDA) clearance to crack, break and dilate stenoses in peripheral arteries and arteriovenous dialysis fistula-associated lesions.

“We have demonstrated XO’s rotating strut technology can crack, break, and dilate intimal and medial calcium,” said Jihad Mustapha (Advanced Cardiac and Vascular Centers for Amputation Prevention, Grand Rapids, USA). “The new 3.8Fr XO RX has a low profile and accommodates 20cm balloons, making it a good option for PAD [peripheral arterial disease] and CLI [critical limb ischaemia] disease. The lower-profile 2Fr version helps address gaps in treatment options currently available for BTK [below-the-knee], tibiopedal and pedal loop stenoses.”

XO RX and XO OTW (over-the-wire) exoskeleton devices include up to 22 rotating struts that slide onto a broad range of off-the-shelf angioplasty balloons, according to a press release from Transit. During balloon inflation, the struts rotate 90 degrees to crack, break and dilate calcified stenotic atherosclerotic lesions, and intimal hyperplastic lesions, and can be used for vessel prep for other treatment options.

“We have seen good results in PTA [percutaneous transluminal angioplasty]resistant intimal hyperplastic and elastic venous lesions in patients with dialysis fistulas with the XO at low nominal or near-nominal pressures,” added Richard Saxon (Tri-City Medical, San Diego, USA). “The new XO RX presents a unique and versatile option for prepping and dilating longer lesion types in patients with severe PAD during limb salvage procedures.”

The XO RX and XO OTW technology is designed to reduce shear and facilitate balloon rewrap by counterrotating 90 degrees upon deflation. Clinicians can deliver fluids from the hub to the balloon before, during or after inflation with XO OTW. No consoles, new capital equipment, or complex learning curve are required, the release adds.

Fresenius Medical Care

Fresenius Medical Care North America’s (FMCNA) Renal Therapies Group recently announced the availability of Speedswap—a new option for the company’s

NxStage System One with NxView that enables the changing of a flowcompromised dialysis filter without replacing the entire cartridge.

As per an FMCNA press release, the new Speedswap system is designed to help reduce therapy downtime, ease nursing workloads, and lower treatment costs, in acute care settings.

Clogging or clotting of the dialysis circuit is a common occurrence associated with continuous kidney replacement therapy in critical care settings, which can lead to therapy downtime, the release also notes. Speedswap allows a flow-compromised NxStage filter to be replaced without replacing the cartridge through the use of a pre-attached, yet detachable, filter.

The system brings to the market two products to be used with the NxStage System One with NxView— Cartridge Express with Speedswap and Speedswap Express Kit—according to FMCNA.

Key features of the Speedswap cartridge system include valves designed to stop the flow of fluid when disconnected and allow fluid to flow when connected; a line restrictor intended to allow for pressure adjustment within the venous and arterial lines, as well as connections to alternate access sources; and pressure oscillating diaphragm (POD) technology to eliminate the blood-air interface and potentially reduce the risk of filter clotting and related therapy interruptions.

Organ Recovery Systems gains exclusive contract for Belgian kidney transplant preservation services Surgeons at Universitaire Ziekenhuizen (Leuven, Belgium) and AZ Universitair Ziekenhuis (Antwerp, Belgium) have successfully performed the first kidney transplant procedures as part of a national contract with Organ Recovery Systems that designates the company as the exclusive provider of preservation services for donor kidneys designated for clinical transplantation.

The arrangement calls for the use of the company’s proprietary LifePort kidney transporter at all transplant centres throughout Belgium along with logistical support services, according to a press release.

LifePort kidney transporter is a novel medical device for organ preservation and transportation that employs hypothermic machine perfusion (HMP) to improve viability of a donor organ during the crucial window of time between organ donation and transplantation, the release also notes.

After being awarded a national contract by the National Belgian Transplant Society for its LifePort technology, Organ Recovery Systems will provide all-inclusive preservation services for all Belgium-based transplant centres from 1 October this year through 2025.

“By establishing LifePort kidney transporter as the standard perfusion technology in Belgium, we are going to show the world what the future of organ preservation looks like,” said Tom Darius (Cliniques Universitaires Saint Luc, Brussels, Belgium). “LifePort kidney transporter gives us the best shot at extending and improving the lives of people in need of a kidney transplant.”

Dialyze Direct has welcomed the American Heart Association’s (AHA) recent scientific statement endorsing home dialysis therapies—including the more frequent haemodialysis (MFD) model of care—in its “Cardiovascular Effects of Home Dialysis Therapies” report, which has been published in the journal Circulation

As per a Dialyze Direct press release, the report encapsulated many of the key research findings that informed the design of the company’s onsite, staff-assisted home dialysis model of care, which is designed to address the challenges of caring for medically complex patients residing in or undergoing rehabilitative/restorative therapies in a skilled nursing facility (SNF).

The report, authored by 12 cardiologists and nephrologists, concluded that ‘more physiologic’ dialysis like the MFD model—when compared with more traditional thriceweekly, in-centre treatments—can lead to “significantly improved outcomes for patients suffering from end-stage kidney disease (ESKD)”, who are up to 20 times more likely to experience cardiovascular-related mortality than the general population.

Earlier this year, Dialyze Direct’s medical professionals validated a new application of MFD for the elderly and frail SNF population with ESKD. The results are published in Hemodialysis International and demonstrate a “marked reduction” in post-dialysis recovery time for these medically complex patients receiving MFD.

Outset Medical resumes shipment of Tablo systems for home use

Outset Medical has announced clearance by the US Food and Drug Administration (FDA) of its previously disclosed 510(k) submission and resumption of shipments of its Tablo haemodialysis system for home use.

In June, Outset implemented a shipment hold on the distribution of its Tablo system pending the FDA’s review and clearance of a 510(k) the company submitted for changes made since the device’s original March 2020 approval.

The company has also reported financial results for the second quarter that ended 30 June 2022 and provided financial guidance for 2022, stating revenue totalling US$25.1 million and a gross margin of 15.1% for the second quarter.

Hansa

Biopharma’s desensitisation

drug gains Scottish Medicines Consortium recommendation

Hansa Biopharma recently announced a recommendation by the Scottish Medicines Consortium (SMC) for its “first-in-class” treatment Idefirix (imlifidase) in the desensitisation of highly sensitised adult patients prior to receiving a kidney transplant from a deceased donor.

The SMC considers Idefirix to be a clinically effective and costeffective treatment, and recognises the significant unmet need of the licensed patient population it treats, as per a Hansa press release.

The recommendation marks an “important milestone” for patients in Scotland, the release adds, as specialised transplant centres will be able to use Idefirix to enable transplantation for highly sensitised patients who are currently “highly unlikely” to receive a lifesaving compatible kidney transplant.

“A lack of effective desensitisation approaches has meant that, until now, people who are classed as highly sensitised kidney patients have struggled to find a donor match, and have often had no alternative but to remain on long-term dialysis with a very poor quality of life,” said Adnan Sharif (Queen Elizabeth Hospital, Birmingham, UK).

“It is fantastic to see that the SMC has followed the direction of England and Wales to offer certain highly sensitised patients the opportunity of a life-altering transplant. The decisionmaking around who has access to the treatment is key, and the lifespan of the transplanted kidneys will need to be carefully monitored. But, success could see many patients gain freedom from gruelling dialysis treatments.”

Earlier this year, alongside its partner Medison Pharma, Hansa also announced that the Polish Ministry of Health had agreed to include Idefirix on its reimbursement list for desensitisation of highly sensitised patients prior to kidney transplantation.

Bluegrass Vascular Technologies has announced that, effective 1 January 2023, it will assume full responsibility for the sales and distribution of the Surfacer inside-out access catheter system.

As the developer and manufacturer of the Surfacer system, as well as the company that successfully implemented all of the regulatory, clinical research and reimbursement initiatives associated with the device, Bluegrass is “well qualified” to take on this responsibility, according to a recent update shared via LinkedIn.

“We have put in place a sales team with extensive experience selling and supporting vascular interventional products and procedures, and have also engaged several experienced Surfacer system proctors to provide our customers first-in-class clinical support,” the update notes.

Earlier this year, Bluegrass also announced it had closed US$5 million in new convertible debt financing.

launches Speedswap to optimise dialysis in acute care setting

Dialyze Direct heralds AHA report endorsing more frequent haemodialysis model of care

Bluegrass Vascular fully responsible for selling and distributing Surfacer system from 2023

Events

15–19 November 2022

VEITHsymposium – 49th Annual Symposium on Vascular and Endovascular Issues New York, USA veithsymposium.org/index.php

23–24 November 2022

European Nephrology Conference Paris, France europe.nephroconferences.com

23–25 November 2022

Paris Vascular Insights (PVI) Paris, France parisvascularinsights.com

23–25 November 2022

Vascular Societies’ Annual Scientific Meeting (VSASM) Brighton, UK vascularsociety.org.uk/asm/vsasm_2022.aspx

17–19 February 2023

American Society of Diagnostic and Interventional Nephrology (ASDIN) Annual Scientific Meeting Orlando, USA asdin.org/mpage/19thannual

30 March–2 April 2023

World Congress of Nephrology (WCN’23) Bangkok, Thailand theisn.org/wcn

11–15 April 2023

National Kidney Foundation (NKF) Spring Clinical Meetings Austin, USA kidney.org/spring-clinical

25–28 April 2023

Charing Cross (CX) Symposium London, UK cxsymposium.com

27–29 April 2023

International Congress of the Vascular Access Society (VAS) Porto, Portugal vas2023.com

Meet our editorial board

Renal

Nicholas Inston

Chairman of the Editorial Board

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 Board Member

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 Board Member

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

Robert Jones Board Member

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