Renal Interventions 1 - EU

October 2021 Issue 01 www.renalinterventions.net

In this issue:

Twelve-month Wrapsody results at CIRSE 2021 page 4

Alexandros Mallios page 12

Dialysis:

Latest debates in dialysis care page 17

Transplantation:

Healthcare disparities in the spotlight page 20

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

Bioartificial device receives KidneyX award after reaching preclinical testing AN IMPLANTABLE BIOARTIFICIAL kidney device (iBAK) has moved closer to becoming a reality after being awarded a US$650,000 prize from KidneyX. The device’s creator, the Kidney Project, received this award following the first ever demonstration of its functional prototype.

The Kidney Project is a US-wide collaboration led by Shuvo Roy (University of California San Francisco [UCSF], San Francisco, USA) and William Fissell (Vanderbilt University Medical Center, Nashville, USA).

In the past few years, it has successfully tested the two essential components that make up its artificial kidney technology—a haemofilter, which removes waste products and toxins from blood, and a bioreactor, which replic ates other kidney functions, like the balance of electrolytes in blood—in separate experiments.

To secure KidneyX’s Artificial Kidney Prize, the team married these two units in a scaled-down version of the artificial kidney that is roughly the size of a smartphone and evaluated its performance in a preclinical model following successful implantation. The units worked in tandem, powered by blood pressure alone, to provide continuous renal replacement therapy without the need for blood thinning or immunosuppressant drugs. This technology, which is intended to provide patients with improved mobility and physiological outcomes compared to dialysis, will now be upscaled for more rigorous preclinical testing and, eventually, clinical trials.

For the latest step forward in the development of this device, the Kidney Project team was awarded KidneyX’s Phase 1 Artificial Kidney Prize—becoming one of six winning teams selected from a field of innovators across Canada, Israel, Japan, The Netherlands, Portugal, Singapore, South Korea, the UK, and the USA. Other recipient technologies included a wearable, lightweight, dialysate-free artificial kidney (US Kidney Research Corporation) and genetically engineered pig kidneys designed to increase supplies of transplantable organs (Makana Therapeutics).

Profile:

iBAK device

(Credit: UCSF)

Follow Renal Interventions on all our social media platforms for the latest news, insight and events in kidney care

The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) have jointly released a report outlining a new race-free approach to diagnosing kidney disease. In its report, the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recommends the adoption of the new estimated glomerular filtration rate (eGFR) 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation that estimates kidney function without a race variable.

and subsequent treatment of kidney diseases,” said ASN president Susan Quaggin. “By recommending the CKD-EPI creatinine equation refit without the race variable, the task force has taken action and demonstrated how nephrology continues to lead the way in promoting healthcare justice.

It is time for other medical specialties to follow our lead, and NKF and ASN stand ready to help however we can.”

In the USA, more than 37 million adults have kidney diseases and 90% are not aware they have diminished kidney function, the NKF-ASN statement adds, with a disproportionate number of these patients being Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian American, and Native Hawaiian or other Pacific Islander. These patient groups also face “unacceptable” health disparities and inequities in healthcare delivery.

he task force has also recommended the increased use of the protein cystatin C—a commonly used biomarker of kidney function—combined with serum (blood) creatinine as a confirmatory assessment of GFR or kidney function. The final report, which has been published online in the American Journal of Kidney Diseases (AJKD) and the Journal of the American Society of Nephrology (JASN), was drafted with “considerable input” from hundreds of patients and family members, medical students and trainees, clinicians, scientists, healthcare professionals, and other stakeholders, to “achieve consensus for an unbiased and most reasonably accurate estimation of GFR”, according to a joint statement from the NKF and the ASN. “This recommendation by the NKF-ASN task force is an important step forward in assuring health and healthcare equity,” said NKF president Paul Palevsky. “We commend the task force for the time, thought, thoroughness and effort it took to explore this issue deeply, and recommend the best path forward for us all. The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race. While the work of the task force is an important initial path forward, both of our organisations are committed to continuing to work to eliminate disparities in the diagnosis and treatment of kidney disease.”

“As the largest organisations representing kidney patients and health professionals, NKF and ASN are committed to eliminating health disparities that harm kidney patients, and ensuring that racial bias does not affect the diagnosis

Developing race-free recommendations Over a 10-month period, the NKF-ASN task force organised its work into three phases. The first involved clarifying the problem and evidence regarding eGFR equations in the USA; the second involved evaluating different approaches to address the use of race in GFR estimation; and the third involved providing recommendations based on this.

In April 2021, the task force published its interim report on reassessing the inclusion of race in diagnosing kidney diseases in AJKD and JASN, asserting that race modifiers should not be included in equations used to estimate kidney function, and that current, race-based equations should be replaced by a substitute that is “accurate, representative, unbiased and provides a standardised approach

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“The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race.”

Paul Palevsky Continued on page 2

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Introduction

Welcome to the first edition of Renal Interventions — a specialised publication providing news and insight to a multidisciplinary audience that includes vascular access surgeons, interventional radiologists, nephrologists, renal nurses and others in the kidney care field.

Headed by a world-leading team of experts, this new offering from BIBA Publishing is now in global circulation.

Subscribe for free and join us on our mission to confront the many challenges, controversies and unanswered questions currently facing kidney disease treatment.

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

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2. Ziv Haskal 5

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Board Member Ziv Haskal is a tenured professor of radiology and medical imaging in the Division of Interventional Radiology at the University of Virginia School of Medicine in Charlottesville, USA. 3. Stephen Hohmann

A word from our editor-in-chief: “Kidney disease is a global problem affecting a huge number of patients in many ways. A varied group of specialists are involved in managing problems relating to kidney failure and its associated complications.

Whether you are a nephrologist, a vascular surgeon, an interventional radiologist, a transplant clinician or a dialysis nurse, the aim of Renal Interventions is to provide you with unique, up-todate and easily readable news and updates on all the latest innovations, research and opinion relating to kidney disease.

The scope of this new publication is wide-reaching and, as few specialists deal solely with interventions in renal care, we feel

that there is a need to bring this all together in one place.

As conferences start to open up again, we could not resist basing our first issue around the vascular access programme at the Paris Vascular Insights meeting.

However, while vascular access is a central theme within the Renal Interventions remit, transplantation, dialysis, interventional nephrology and the wider field of kidney disease care are also key areas of focus.

I welcome you and your team to Renal Interventions, and look forward to joining you as part of the broad community aiming to improve the management, and the lives, of those with kidney disease.” – Nicholas Inston

Board Member Stephen Hohmann is a vascular and general surgeon at the Texas Vascular Associates clinic in Dallas, USA. 4. Robert Jones Board Member Robert Jones is an interventional radiologist at Queen Elizabeth Hospital Birmingham in Birmingham, UK. 5. Haimanot Wasse Board Member Haimanot Wasse is the director of interventional nephrology and a professor of medicine at Rush University Medical Center in Chicago, USA.

Renal community reckons with removal of race variable in kidney disease diagnosis Continued from page 1

to diagnosing kidney diseases”. The final report, which is authored by co-chair of the NKF-ASN task force Cynthia Delgado and colleagues, lists three key recommendations to this end.

Chief among these recommendations is the immediate implementation of the new CKD-EPIcr_R equation—which excludes race in the calculation and reporting of eGFR, included diversity in its development, is immediately available to all laboratories in the USA, and has “acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals”.

The task force’s second recommendation highlights the need for efforts to facilitate the increased, routine and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for, or have, CKD. It also notes that combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than the use of either one marker alone. The third and final recommendation states that research on GFR estimation with new endogenous filtration markers, and on interventions to eliminate racial and ethnic disparities in kidney disease, should be encouraged and funded—with the “ultimate goal” of promoting health equity.

“This unified approach, without specification of race, should be adopted across the USA,” the report adds.

“High-priority and multistakeholder efforts should implement this solution.” The NKF and ASN are now encouraging the Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) to develop updated guidelines that “ensure a uniform approach consistent with the task force’s recommendations”.

New research on eGFR The release of the NKF-ASN task force’s final report coincides with several research articles being published online that support this new approach to GFR estimations. One such piece of research, authored by Alan Go (Kaiser Permanente Northern California, Oakland, USA) et al in the New England Journal of Medicine (NEJM), notes that the inclusion of race in equations to estimate GFR has become “controversial” and details a national study involving cross-sectional analyses of baseline data from 1,248 adult CKD patients.

Go et al conclude that, in the study, the use of the serum creatinine level to estimate GFR without race (or genetic ancestry) introduced “systematic misclassification” that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for, but estimations of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of current race-based approaches.

Another report published in NEJM by Lesley Inker (Tufts Medical Center, Boston, USA) et al details efforts to develop new, race-free eGFR equations using data from thousands of participants—and concludes that “new eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate, and led to smaller differences between Black participants and non-Black participants, than new equations without race with either creatinine or cystatin C alone”.

Publisher: Roger Greenhalgh | Content Director: Urmila Kerslake | Editor: Jamie Bell jamie@bibamedical.com Editorial contribution: Jocelyn Hudson, Bryan Kay | Design: Terry Hawes, Wesley Mitchell Advertising (EU): Rebecca Djaic rebecca@bibamedical.com | Advertising (US): Nicole Schmitz nicole@bibamedical.com Subscriptions: subscriptions@bibamedical.com | News or advertising queries: Tel: +44 (0)20 7736 8788 Published by: BIBA Publishing, which is a subsidiary of BIBA Medical Ltd BIBA Medical, Europe, 526 Fulham Road, Fulham, London, SW6 5NR, United Kingdom Tel: +44 (0) 20 7736 8788 | BIBA Medical, North America, 155 North Wacker Drive, Suite 4250, Chicago, IL 60606, United States Tel: +1 708-770-7323 Printed by: Buxton Press Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the United Kingdom address. © BIBA Medical Ltd, 2021. All rights reserved.

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Renal Interventions October 2021 – Issue 1

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Arteriovenous Grafts

First-in-human WRAPSODY FIRST study demonstrates “very encouraging” 12-month results Twelve-month results from a first-inhuman study of the Wrapsody cellimpermeable endoprosthesis (Merit Medical Systems) for the treatment of access circuit stenosis in haemodialysis patients are “very encouraging”. This is according to James Gilbert, a consultant transplant and vascular access surgeon at the Oxford University Hospitals NHS Foundation Trust in Oxford, UK, and president of the Vascular Access Society of Britain & Ireland (VASBI), who presented these data for the first time at the Cardiovascular and Interventional Radiological Society of Europe 2021 summit (CIRSE; 25–28 September, virtual).

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ilbert noted that this first-in-human study—dubbed WRAPSODY FIRST— produced positive results in terms of safety, detailing that no adverse events confirmed as being device-related were observed in 39 patients at one-year follow-up. Regarding effectiveness, he reported promising target lesion primary patency (TLPP) rates at 12 months across all lesion sites, in line with the study’s six-month data, and stated that access circuit patency rates also appear to remain high following treatment with the device. Gilbert went on to detail the pivotal WRAPSODY WAVE trial—a global randomised controlled trial (RCT) that is currently underway to assess the Wrapsody endoprosthesis.

Speaking to Renal Interventions, Gilbert said:

“The 12-month effectiveness data, particularly of TLPP, are very exciting because we may have a stent that requires fewer reinterventions to maintain patency at the lesion site and, more importantly, ensures that the access circuit remains functional—which is key for any dialysis patient.

The data were also reproducible at all lesion sites treated within the access circuit, from the cephalic arch in a brachiocephalic AVF [arteriovenous fistula] to the graft vein anastomosis site and the central veins. This is suggestive that there is something about the stent’s design, with its cell impermeable middle layer and softened end rows, that is key in minimising edge stenosis at both ends of the stent.

“We recognise that these very encouraging data are only from a small, first-in-human study and so the WRAPSODY WAVE trial will be key in confirming just how good this stent can be.

The WAVE study will not only provide a bigger number of patients in which to assess the effectiveness of the stent, it will also provide experiences from a range of expert clinicians globally.”

Addressing the CIRSE audience, Gilbert described the Wrapsody endoprosthesis as a “unique, tri-layered stent graft” that is currently CE-marked for use in Europe and is available in sizes ranging from 6mm to 16mm, making it a viable treatment option for a “huge range” of stenotic lesions, including those in the peripheral and central veins of an access circuit.

Gilbert went on to detail the design and purpose of WRAPSODY FIRST—a prospective, three-centre, single-arm, first-in-human feasi-

Key findings:

84.6% 12-month target lesion primary patency rate

65.9% 12-month access circuit primary patency rate

Wrapsody endoprosthesis

Bright future for access grafts highlighted at VASBI 2021 with multiple novel technologies New technologies intended to improve the often mixed outcomes associated with arteriovenous grafts (AVGs) for haemodialysis access were on display at this year’s Vascular Access Society of Britain & Ireland scientific meeting (VASBI; 16–17 September 2021, virtual). In addition to insight on the Wrapsody endoprosthesis (Merit Medical Systems) from James Gilbert (Oxford University Hospitals NHS Foundation Trust, Oxford, UK), two other innovative grafts— each designed to tackle unique, unresolved problems in this space—featured prominently.

THE SESSION, ENTITLED “UPDATES AND Developments in Dialysis Access”, first saw Jeffrey Lawson, adjunct professor of surgery at Duke University Medical Center (Durham, USA) and chief surgical officer at Humacyte, present the human acellular vessel (HAV; Humacyte)—a bioengineered graft intended for use in haemodialysis access, as well as vascular trauma and peripheral arterial disease (PAD). He initially noted that synthetic graft products, often made from expanded polytetrafluoroethylene (ePTFE), are already in use in the USA due to high non-maturation rates associated with arteriovenous fistulas (AVFs), but that only about 70% of these remain functional as a dialysis access option at October 2021 – Issue 1

one year due to either infection or failure modes at the anastomosis.

Lawson claimed that the HAV, which is grown from human vascular smooth muscle cells, is usable within one month Jeffrey Lawson of implantation, and appears to be highly resistant to infection and has demonstrated long-term durability and limited intimal hyperplasia in ongoing clinical studies. Referencing results from a Phase II study of the HAV for haemodialysis Shawn Gage access specifically, he reported improved six- and 12-month secondary patency rates compared to historical data on autologous fistulas and ePTFE grafts, in addition to reduced infection rates and positive safety outcomes.

Lawson claimed that the HAV has displayed an ability to repopulate and remodel itself with the patient’s own cells over time, and has also been shown to not stimulate an immune response, with no reported instances of clinical graft rejection across more than 430 patients. Fiveyear results from end-stage renal disease (ESRD) patients implanted with the HAV in the Phase II study have been submitted for publication, he added, and two multicentre, Phase III studies are now ongoing to directly compare the bioengineered graft to traditional AVFs and AVGs.

bility study assessing the safety and effectiveness of the device, for which he is the primary investigator. The subject population consisted of dialysis patients with AVFs or arteriovenous grafts (AVGs) in their upper limbs, who experienced stenosis or occlusion within their access circuit. Gilbert reported the primary safety objective as being the proportion of patients without any localised or systemic safety events affecting the access or venous outflow circuit, and resulting in surgery, hospitalisation, or death, while the primary effectiveness objective was TLPP. Follow-up took place at 30 days, three months, six months and 12 months, he added.

Gilbert stated that a total of 46 patients were enrolled in the study, with outcome data for 39 patients ultimately being available beyond one year. On safety outcomes at 12 months, he reported a total of five adverse events, four of which were adjudicated as being procedure-related, with the access circuit not being salvaged and a lack of imaging data making it impossible to determine if the one remaining event—a thrombosed fistula—was device- or procedure-related.

Touching on effectiveness next, Gilbert described the 12-month TLPP rate of 84.6% as “very encouraging”, and similarly positive to the 97.7% TLPP rate seen at six months, before reporting that reintervention was successful in all problematic cases—resulting in a 12-month assisted TLPP rate of 100%. Further, he noted an access circuit primary patency rate of 65.9% at 12 months. All but five of the remaining access circuits were salvaged via reintervention, he added, leading to a secondary patency rate of 88.6%. These data are also published in CardioVascular and Interventional Radiology (CVIR).

Gilbert concluded his presentation by conveying details of the WRAPSODY WAVE trial, which is a multicentre RCT designed to further assess the Wrapsody endoprosthesis as a treatment option for dialysis access circuit stenoses and support US Food and Drug Administration (FDA) approval of the device. This trial is already underway, and will involve 1:1 randomisation of patients across two study arms comparing Wrapsody to percutaneous transluminal angioplasty (PTA)—in addition to a third, registry-based arm assessing the device’s use at the graft-vein anastomotic site.

Later in the same session, Shawn Gage—an adjunct instructor for the Duke University Physician Associate Program (Durham, USA)—presented the InnAVasc graft to the VASBI audience. Gage, who is also InnAVasc founder and director of clinical operations, began by highlighting the many issues in dialysis access including haematoma, external bleeding, pseudoaneurysm and localised infection, that stem from problems with graft cannulation. He also pointed to a report published in the Journal of Vascular Access (JVA) that suggests that, across traditional AVGs and AVFs, needling complications may account for as much as 20% of all access-related complications.

Gage then discussed the InnAVasc graft in more detail— stating that it has been designed to prevent these complications with features such as cannulation pods and ridges that give the cannulator a very specific and identifiable site to puncture, a back plate that prevents the needle from puncturing the other side of the graft, and self-sealing materials that reduce or eliminate bleeding. In addition to noting that no needle-related complications or injuries have been observed in the graft across 42 patients and 5,500-plus cannulations, Gage claimed that cannulation complications are likely to be a bigger problem than is currently being recognised in dialysis access, with further research and improved materials being required to ameliorate this situation.

Gage went on to discuss how improved safety features like those seen in the InnAVasc graft could represent a major advantage for patients interested in transitioning to home haemodialysis and hold the potential to bring about a new generation of home therapies for kidney failure patients.

Vascular Access Tools

New vascular access handbook intends to provide dialysis patients with answers “once and for all” At the 12th Congress of the Vascular Access Society (VAS; 6–9 April 2021, online), Ramon Roca-Tey, senior consultant in nephrology at the Fundación Sanitaria Mollet’s Hospital de Mollet in Barcelona, ​​Spain, and president of the Spanish Multidisciplinary Group for Vascular Access (GEMAV), presented audiences with the “Vascular access handbook for people with kidney disease”—noting that, with this handbook, “a need has finally been met”. Following the congress, Roca-Tey spoke to Renal Interventions to discuss this educational tool in more detail.

Briefly, what is the vascular access handbook?

With this handbook, we have tried to develop a really useful and practical tool for people with kidney disease. It is about transmitting information to these people in a simple and clear way so that they can resolve any doubts they may have regarding vascular access for haemodialysis.

Why was it introduced?

It was introduced to adapt the most important aspects of the 2017 Spanish Clinical Guidelines to the reality of people with kidney disease.

This handbook aims to help people with kidney disease so that they can find the answers to some aspects of vascular access for haemodialysis once and for all.

What is the “unmet need” you feel the handbook fulfills?

Some people with kidney disease are not aware of the importance of vascular access for haemodialysis and the care it requires. I think the handbook can help a lot in this regard.

The handbook uses minimal text, non-technical language and many illustrations—why is this?

In order for the handbook’s information to be understood correctly by as many people as possible, we have included a minimal amount of text, making it as colloquial as possible while avoiding technical words. We have also included many illustrations—because an image is worth a thousand words—as well as nine educational videos.

Could you outline the “active role” the patient plays within the multidisciplinary team?

The handbook underlines that the patient with kidney disease is at the centre of the multidisciplinary team and, therefore, is also responsible for their own fistula care. This concept is present in almost all handbook sections.

How has the handbook helped dialysis patients who have used it?

We have had a lot of feedback. For example, some people mistakenly thought—before read-

Vascular access handbook

Ramon Roca-Tey

ing the handbook—that, during native fistula surgery, they would have a device fitted. Other people were unaware of the fistula maturation procedures or how to care for their venous catheter.

How important do you think the handbook could prove to be for physicians?

I think it will be very important for physicians too, as it will help prevent many complications related to vascular access, such as fistula thrombosis and catheter infection.

Who is the handbook currently available to?

Both Spanish and English versions of the handbook are available free of charge to everyone on the GEMAV website (www.gemav.org). In Spain, we have obtained funding to print this handbook so that each of the 25,000 prevalent haemodialysis patients in the country will receive a paper copy of it.

Why did you decide to translate the handbook into English?

So that it can reach the largest possible number of people with kidney disease around the world.

Are there any future plans for the handbook right now that you could outline?

Yes, it is already being translated into other languages—specifically, French, Polish, Swedish and Hebrew—and has also been uploaded to the websites of the many scientific societies that have endorsed it, including VAS, the American Society of Diagnostic and Interventional Nephrology (ASDIN), and the European Kidney Patients’ Federation (EKPF).

How will the handbook impact dialysis care?

I hope that it will help as much as possible to overcome challenges in vascular access for people with kidney disease—both in the present and in the future.

— Images used with permission from the author.

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Individualised approach boosts chances of selecting the right dialysis access option Among discussions on the opening day of the Vascular Access Society of Britain & Ireland 2021 scientific meeting (VASBI; 16–17 September, virtual), Charmaine Lok—a professor of medicine at the University of Toronto, and medical director of the Chronic Kidney Diseases and Haemodialysis Programmes at Toronto General Hospital (Toronto, Canada)—outlined her algorithm for selecting the most appropriate type of dialysis access for patients needing kidney replacement therapy (KRT). Lok also directed attendees towards multiple tools that she believes are helpful in this decision-making process.

She said her initial considerations are what the patient’s unique situation is, including where they currently are on the chronic kidney disease (CKD) management continuum. “This is really important because it tells me how much time I have to develop a PLAN [Patient Life plan and Access Needs], as well as how and when to create a dialysis access,” Lok added. She also noted that, broadly speaking, a multidisciplinary team is needed here, with nephrologists helping to develop a patient life plan, while operators—vascular access surgeons, interventional radiologists and interventional nephrologists—are critical in determining the patient’s access needs.

“If you think about your patient’s circumstances, characteristics and preferences, then you are unlikely to go wrong.”

Charmaine Lok

Lok went on to discuss how an individualised approach can then be spun out from considerations of the patient’s clinical circumstances, including but not limited to cardiac function, vessel characteristics and likelihood of long-term survival, and also their personal preferences. “In my algorithm, if the patient is young and has a higher chance of long-term survival, I would typically prefer to have an arteriovenous (AV) access— hopefully a fistula,” she stated. “However, in some situations, a central venous catheter (CVC) is very valid and appropriate, and we need to be mindful of the patient’s individual circumstances when making this choice.”

She also acknowledged the importance of having a backup plan as deviations from the original life plan may be required if the urgency of the patient’s situation changes—a scenario that can truncate the planned timeline, from years or months to weeks or days. Lok noted that this is not an uncommon occurrence, as 20–40% of all dialysis starts are urgent rather than planned, adding that an early-cannulation arteriovenous graft (AVG) may be the best way forward in these instances.

Lok then highlighted other tools including the Kidney Disease Outcomes Quality Initiative (KDOQI) and also the My Vascular Access application (www.myvascularaccess.com/ home)—a simple, evidence-based tool that can ascertain the patient’s characteristics and rank the appropriateness of different access solutions.

Summarising her own algorithm, Lok said she considers the patient’s unique situation first, before moving on to develop a CKD life plan and select an access option. “If you think about your patient’s circumstances, characteristics and preferences, then you are unlikely to go wrong,” she concluded.

Issue 1 – October 2021

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Fistula Maturation

Timely balloon angioplasty vital to aid slow-maturing fistulas

Oversized balloon angioplasty technique safe and effective for fistula maturation

Tackling the main culprit in slow-to-mature arteriovenous fistulas (AVFs), stenosis in the anastomosis and outflow veins, with balloon angioplasty before it is “too late” can boost maturation rates. Robert Jones (Queen Elizabeth Hospital Birmingham, Birmingham, UK) set out his endovascular treatment strategy for balloonassisted maturation at this year’s Vascular Access Society of the Americas Spring Virtual Conference (VASA 2021, 21–22 May, online).

A retrospective analysis published in the Journal of Vascular Access ( JVA) has shown that the oversized balloon angioplasty technique to assist arteriovenous fistula (AVF) maturation is safe and effective—and allows cannulation of the fistula within hours or days of the procedure, decreasing the time a central venous catheter (CVC) needs to be used for.

“W

hen and how do we best pick up a slow-tomature fistula with a view to intervention?” asked Jones, going on to frame the relatively narrow window for maturation interventions with the statement: “If a fistula has not matured by four to six weeks, it is unlikely to.”

This time window charts the latest Kidney Disease Outcomes Quality Initiative (KDOQI) guideline that considers it reasonable for operators to evaluate for postoperative complications within two weeks [of access creation] and an appropriate member of the vascular access team to evaluate for AVF maturation by four to six weeks after.

Jones also touched on an important-to-recognise later presentation scenario that could prompt endovascular intervention—when maturation failure is identified later on by unsuccessful attempts at fistula cannulation.

Up to 50% of fistulas need help to mature Postoperative arteriovenous access maturation rates can vary, according to Jones, but roughly half of all fistulas will need at least one intervention before they are functional and can adequately support dialysis. Stenosis is the main offender in the slow-to-mature fistula and most commonly occurs in the juxta-anastomotic region. Accessory side-branch veins can also be responsible for slow maturation in 30–50% of cases, and can occur in isolation or in association with stenosis.

Again, referring to the KDOQI guideline that states good-quality studies comparing surgical and endovascular techniques for postoperative maturation are either lacking, or have conflicting results, Jones highlighted that an individualised patient approach with a first-line endovascular strategy is customary in this nearly fact-free zone.

“Despite there being little high-quality data that directly compare maturation rates achieved using endovascular interventions against those achieved with surgery, balloon-assisted maturation takes centre stage, and I often consider a brachial artery access using a micro-puncture kit to get a diagnostic fistulogram as a roadmap in the first instance at the time of intervention,” he said.

The road to balloon-assisted maturation Jones recommended an endovascular plan to treat maturation failure that begins with a physical exam to locate the type and level of the lesion. This is followed by an ultrasound exam to confirm these findings; exclude any thrombosis; and assess the depth of the fistula. “Ultrasound can also identify accessory veins,” clarified Jones. Finally, a fistulogram and intervention complete the pathway. “This [fistulogram] allows us to create a definitive roadmap and anatomical assessment to map out where the stenosis and accessory veins are, and the relevant lesion is then treated,” he said.

Jones urged consideration of the whole access circuit with a reminder that stenoses in the arterial circuit can occur quite proximally and could therefore require additional cross-sectional imaging in a small number of cases—especially when a peripheral lesion cannot be identified using standard assessment. “I tend to start with a 0.018-inch balloon platform, then move to a high-pressure balloon, if necessary,” he stated. “If unsuccessful, I move to a cutting balloon.”

On managing branch veins, Jones suggested adopting a ‘watch and wait’ strategy to see how the fistula fares after balloon maturation—but added that compressing the vein under ultrasound to determine its significance and inform the appropriate intervention is also an option.

October 2021 – Issue 1

“There is evidence supporting repeated sequential angioplasty produces a good result, and this is often required to achieve continuity in outflow from the artery to the vein and a fairly uniform vessel that will go on to mature,” Jones added. Complications can occur, and include haematoma, extravasation from rupture, and thrombosis, which the literature states are most commonly seen in forearm fistulas, he cautioned.

Primary patency outcomes of endovascular maturation are reported to be slightly inferior to those achieved with surgery, as determined by Jan Tordoir et al in a systematic review published in the European Journal of Vascular and Endovascular Surgery (EJVES) in 2018. The review also reported clinical success rates with endovascular maturation procedures in the range of 43–97%.

Jones pressed home the importance of secondary patency in fistula intervention and the benefit that the minimally invasive balloon-assisted maturation strategy conveys, with rates reported to be 68– 96% in the systematic review.

“In summary, balloon-assisted maturation can increase the number of functional fistulas: get in there early with a three-step management approach involving the physical exam, ultrasound and then, finally, intervention,” Jones stated. “Remember to consider the whole access circuit, and you are looking to treat stenosis and accessory veins.” Looking to the future, Jones told Renal Interventions more data are required here, and that it would be particularly interesting to determine the value of drugcoated balloons (DCBs) in treating immature fistulas. “To date, studies have examined the application of DCBs in treating dysfunctional fistulas already in use, with only a few cases reported of this application in the immature fistula,” he noted.

“Balloon-assisted maturation can increase the number of functional fistulas: get in there early with a three-step management approach involving the physical exam, ultrasound and intervention.”

Robert Jones

IN THEIR JVA REPORT, LEAD AUTHOR Leonardo de Oliveira Harduin (LivCare Centro Clínico, Rio de Janeiro, Brazil) and colleagues write: “In the present study, the vast majority of fistulas unsuitable for cannulation eight weeks after creation became a functional vascular access for haemodialysis following balloon angioplasty. In this series, technical and clinical success was achieved in 91% of cases. Previous studies have demonstrated comparable technical success, ranging from 74% to 97%, with use of an endovascular technique for AVF maturation based on balloon angioplasty.”

The researchers conducted a single-centre, retrospective chart review on the records of patients who had undergone AVF creation, but whose fistula had failed to mature and was

91% 74–97% Rate of technical and clinical success in this series

Success rates in previous studies

not fit for use in dialysis access eight weeks after the procedure, and later received endovascular therapy to assist fistula development. Flow volume, time interval of fistula use and catheter removal, and patency and complication rates, were all evaluated. From October 2011 to January 2019, 78 patients underwent 124 balloon angioplasty procedures for assisted AVF maturation, Harduin et al report, all of whom were on long-term haemodialysis through a catheter.

Technical and clinical success was achieved in 91% of patients across the review, while seven patients were excluded.

In patients with successful maturation, no residual stenoses were identified at angiography, the vein became palpable throughout the matured segment and the average flow volume was 1014ml/min 24 hours after the procedure.

The mean time to first AVF use after maturation was five days and, on average, catheter removal was performed 14 days after the maturation procedure. In the 71 patients who experienced technical and clinical success, the primary patency rate at three, six and 12 months was 87.3%, 66.2%, and 50.7%, respectively.

Across the 124 procedures, minor complications occurred in 22 patients (18%), and six had major complications (4.8%). During follow-up, 24 patients required an additional procedure and 11 required two additional procedures for fistula maturation and patency maintenance.

Fistula Maturation

Combination therapies and dynamic fistulas offer promise in boosting maturation rates Arteriovenous fistulas (AVFs) are widely considered to be the holy grail in dialysis access, providing a more long-term solution than synthetic arteriovenous grafts (AVGs) or central venous catheters (CVCs), with a reduced risk of complications. However, these benefits only come into play once the fistula has become functional—prior to this stage, they carry their own set of potential drawbacks with the major one being a risk of non-maturation, whereby the fistula is still not providing a suitable dialysis access option several weeks after surgery. Joris Rotmans, chair of the Department of Nephrology at Leiden University Medical Center in Leiden, The Netherlands, and president-elect of the Vascular Access Society (VAS), discusses why AVFs achieve maturation so inconsistently and outlines ongoing efforts to solve this longstanding problem.

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he problem of AVF non-maturation ultimately stems from the fact that a fistula is an artificial connection, which disturbs the natural homeostasis in a vein by instigating an excessively high rate of blood flow. “In general, [AVF creation] is unphysiological,” Rotmans states, “because we want the veins to do something that they are not designed to do.” He goes on to note that, while current European guidelines still lean towards a fistula-first approach to dialysis access, there has been a slight shift away from this within US guidance in recent years, in particular when it comes to elderly patients, due to the lengthy maturation period and potential secondary interventions associated with AVFs. Various clinical studies have indicated that roughly 50% of patients need at least one subsequent intervention to make their fistula functional and, overall, about 75% of fistulas end up achieving maturation—a fact that, according to Rotmans, will frequently lead to patients choosing an AVG or CVC instead, especially in countries where shared decision-making is more prevalent across healthcare systems. “However, once you have a functional fistula, the complication rate is by far the lowest compared to other access options,” he continues. “It is the early phase where there are a lot of hurdles but, once it is up and running, everybody is convinced that it is the best option.”

Risk factors for non-maturation “In terms of risk factors, female sex is the most important by far,” Rotmans notes. “Women have an almost two-fold increased risk of non-maturation, and that is consistent in numerous studies from all over the world.” He goes on to state that the underlying causes of this phenomenon have not yet been uncovered, with the initial theory attributing it to female patients having smaller blood vessels also being ruled out as an explanation by these studies.

“In the current guidelines, in my opinion, female sex is not being recognised enough, because there is no differing policy with regard to selecting the optimal access in female patients compared to male patients—and, I think that, when you are anticipating the risk of non-maturation, the sex of the patient should be considered in the equation,” he adds.

While older age and previous cardiovascular disease have both been highlighted as potential risk factors for non-maturation in some studies—but not unequivocally proven to date—the previous use of CVCs, as well as other instances of needling in the blood vessels themselves prior to fistula creation, are more well-established as being associated with a heightened risk of non-maturation, with “feed preservation” therefore being encouraged in the lead up to a patient beginning dialysis. Rotmans notes that the access surgeon’s level of experience is important in fistula outcomes as well—but is arguably the most challenging factor to quantify with data.

Multifaceted approach needed?

The possibility of directly aiding AVF maturation is still an area shrouded in uncertainty. Previously, animal models and preclinical studies have indicated that elastin plays a notable role in fistula maturation. However, subsequent clinical trials showed no substantial benefit to modifying

the levels of this protein in the vessel walls of patients.

Similarly, Rotmans says, there was previously a belief that inhibiting the overall inflammatory response caused by AVF creation may improve maturation rates—but, once again, clinical trials involving liposomal prednisolone for this purpose yielded disappointing results.

Rotmans goes on to state that translating the role played by these specific proteins and factors into clinical benefits is challenging because there are numerous interlinked processes involved in fistula maturation. “There are hundreds of genes involved here and modulating one of them is not going to make a difference for patients in the future, in my opinion,” he adds, claiming that, because of this, a combination therapy may be required to change this uncertain outlook. “You really need to influence multiple pathways to steer the vessel in the right direction,” he says. “So, I am convinced that the local administration of drugs—during surgery, or by clever labelling to guide them to the vascular access site—is the way to influence maturation.”

A dynamic solution Tackling the problem of fistula maturation at the source is another approach that is currently being investigated, according to Rotmans. More specifically, reducing the consistently high rate of blood flow through the anastomosis—which is a “substantial part” of the problem of non-maturation and also plays a role in long-term fistula failure—has been explored, with creation above the elbow

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or in the upper arm (brachiocephalic), where the vessels are larger and can cope with higher flow, sometimes being preferred to the lower arm (radiocephalic). While there is evidence this approach can reduce non-maturation by as much as 50%, Rotmans claims the higher blood flow in upper arm fistulas creates a fresh set of problems, leading to excessive cardiac output and a greater burden on the heart. “That is one way to circumvent non-maturation but, for me, not the preferred way, because it comes with its own complications in the long term,” he adds.

However, another more novel method for influencing haemodynamics in AVFs may be on the horizon, Rotmans says—one that he describes as a “dream solution” in non-maturation. “Ideally, we would have a fistula or vascular access in place that is only functioning during dialysis,” he states. “That would be my ultimate goal.” The phenomenon Rotmans refers to here has been dubbed a ‘dynamic fistula’, whereby a remotely operated valve inside the device can substantially reduce the flow rate through the anastomosis in between dialysis treatments.

He notes that the device is currently on the path towards preclinical studies, with data on its safety and efficacy in animal models expected in 2022, but that it may be three or four years before it is ready for widescale clinical trials.

Novel technologies and future research There is no shortage of further, alternative solutions to non-maturation that are being researched presently.

The FA-1 (Fist Assist Devices) and Amplifi (Artio Medical) systems, which are designed to promote vein dilation prior to surgery and boost AVF maturation rates, are interesting recent introductions in this space, according to Rotmans—with the former recently gaining US Food and Drug Administration (FDA) approval and the latter currently in first-in-human studies. Meanwhile, Rotmans describes the growing body of evidence on drug-eluting balloons for dysfunctional AVFs as “promising”, but adds that more studies are required to unravel why there are disparities between the findings of different trials in this space.

Other areas that Rotmans believes warrant further research range from the use of postoperative ultrasound to predict non-maturation—and the benefits of subsequently intervening at an earlier point in time—to the use of artificial intelligence (AI) as a tool for predicting AVF flow profiles, which he adds is an area of “great interest”.

“In general, I think we should focus on the haemodynamics in fistulas, and look at a combined therapeutic approach that interferes with multiple pathways at multiple timepoints—we should stop thinking about one solution for the whole problem,” he concludes. “But, it will not be easy to identify optimal timings, dosages and combinations. That will be enough work to occupy everyone involved for the next couple of decades.”

50%

Patients that need at least one reintervention to make their AVF functional

75%

AVFs that end up achieving maturation

Joris Rotmans

Issue 1 – October 2021

Vein Dilation

Global FACT trial reports significant superficial arm vein dilation with FA-1 device

Results from first-in-human study of Amplifi vein dilation system presented at VIVA 2021 Preliminary clinical results from a first-in-human study assessing the Amplifi vein dilation system (Artio Medical) were presented at this year’s Vascular InterVentional Advances conference (VIVA; 4–7 October 2021, Las Vegas, USA).

Data were presented by Surendra Shenoy—an associate professor of surgery at the Washington University School of Medicine at Barnes-Jewish Hospital in St Louis, USA—during the event’s final late-breaking clinical trial session.

Fist Assist Devices has announced completion of the FACT trial, which evaluated the use of its FA-1 intermittent pneumatic compression device to promote vein dilation in kidney disease patients. The trial’s results suggest the device could enable an increase in the creation of functional arteriovenous fistulas (AVFs) by enlarging superficial veins, and demonstrates its safety in this patient population.

“THIS IS GROUNDBREAKING research that will drive efficiencies in the end-stage renal disease community, as it really proves that intermittent compression enlarges superficial veins, and larger veins provide better surgical or endoAVF options and outcomes,” said John Ross (Regional Medical Center, Orangeburg, USA).

Patients were enrolled in the FACT trial at three locations: The University of Chicago Medical Center in Chicago, USA; a medical clinic in Greenwood, USA; and MS Ramaiah Medical Center in Bengaluru, India. On preliminary analysis, most enrolled patients showed statistically significant superficial vein dilation (p<0.05) without any safety concerns.

“We are ecstatic to complete FACT, and are very thankful to all patients, physicians and hospitals that worked to complete this trial during the COVID-19 pandemic—which was possible as the device is a patient-centric wearable in the home,” said Mary Hammes (University of Chicago), the trial’s primary investigator.

The FA-1 device is approved for use in arm massage and increased vein circulation in the USA—having gained US Food and Drug Administration (FDA) approval for this indication in June 2021—and is cleared for use in increased forearm vein enhancement and AVF dilation/maturation in India, Canada, Europe, Australia, and New Zealand.

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he Amplifi system is designed for percutaneous placement and up to 14 days of use to stimulate arm vein enlargement in haemodialysis patients using rapid, non-pulsatile, venous blood flow. The device includes a wearable, external blood pump, inflow and outflow catheters, and a controller, all of which are removed during arteriovenous fistula (AVF) creation.

Data presented at VIVA came from the first five patients treated by Adrian Ebner, head of the Cardiovascular Department at Sanatorio Italiano Hospital in Asunción, Paraguay, in a prospective, non-randomised, single-arm, first-in-human clinical study with the Amplifi system.

These data demonstrated that forearm and upper arm mean cephalic vein diameters had more than doubled over an average treatment period of 8.6 days. AVFs were successfully created using treated veins in all patients.

Maturation data are available for the first three patients and show that both the forearm and upper arm AVFs matured quickly with mean outflow vein diameters of 7mm and a mean blood flow rate of more than 1,000 ml/ min after a six-week maturation period. No device-related or procedural adverse events were observed.

“Not long after AVFs were first pioneered for haemodialysis in 1966 by doctors Cimino, Brescia, and Appel, concerns were raised about patients who were not suitable for AVF surgery and the high rate of AVF maturation failure,” Shenoy said. “Despite these challenges, AVF remains the preferred option for most patients today. The Amplifi system is the first device I have seen that has real potential to address both of these challenges in a major way—to make good on the promise of providing reliable, long-lasting vascular access sites for this unique and vulnerable patient population.”

Artio is now planning to set up a US clinical trial of the Amplifi vein dilation system in 2022.

Amplifi vein dilation system

Mary Hammes

John Ross

Rates and survival of fistulas remain stable in 39-year Danish study Despite an older dialysis population, the proportion and survival of arteriovenous fistulas (AVFs) in Danish dialysis patients has not changed over a 39-year period. This is the main conclusion of a national cohort study published in the Journal of Vascular Access ( JVA).

AUTHORS KRISTINE LINDHARD (HERLEV Hospital, Herlev, Denmark) and colleagues suggest that this is probably because of increased awareness of AVF as the first choice of vascular access and improved surveillance, surgery and repair. Lindhard et al write that the age and number of comorbidities in the haemodialysis popu-

lation has increased over time, which, they hypothesise, may influence the construction and survival of AVFs. In the present study, the research team explored the incidence and survival of AVFs between 1977 and 2015 by conducting a retrospective cohort study based on Danish registries.

The authors note that the registries included 10,187 arteriovenous accesses (AVFs and arteriovenous grafts) and 4,201 central venous catheters (CVCs). They report seeing no significant difference in the proportion of AVFs during the 39 years. In addition, they found that age and renal diagnosis did not influence the proportion of AVFs, and that patients with CVCs were found to have a signifi-

cantly higher prevalence of comorbidities.

Another key finding was that AVF survival remained stable during the 39 years. Lindhard and colleagues add that the first constructed AVF had the best survival with 35% still functioning after 15 years. Factors such as brachiocephalic AVF (odds ratio [OR], 2.46; 95% confidence interval [CI], 2.29–2.65), female sex (OR, 1.17; 95% CI, 1.1–1.25) and diabetic nephropathy (OR, 1.21; 95% CI, 1.12– 1.3) increased the risk of AVF failure, the authors detail.

In the discussion of their findings, they highlight some key strengths of their study, including the large sample size, long observation period of 39 years and high data completeness in the Danish registries.

However, they also acknowledge certain limitations.

For example, the Danish Nephrology registry was first completed after 1 January 1990 and some dialysis treatments before this time may not have been registered.

Another limitation is the lack of data on CVC history, medication and time to cannulation.

Issue 1 – October 2021

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Profile

Q&A

Alexandros Mallios Born and raised in the small lakeside city of Kastoria in northern Greece, Alexandros Mallios’ 15-year journey as a vascular surgeon has seen him complete a year of national service in the Greek military, travel to far-flung parts of the Caribbean and Central America to perform complex procedures, and work with a number of pioneering physicians in the field. Today, he is the director of the Vascular Access Center at Hôpital Paris Saint-Joseph in Paris, France and chief of vascular surgery at Centre Hospitalier de Chartres in Le Coudray, France. His achievements include pioneering and performing the first ever percutaneous arteriovenous fistula (pAVF) creation with the Ellipsys system (Medtronic) in Europe, and co-founding the Paris Vascular Insights (PVI) conference.

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

Believe it or not, I decided to study medicine because I was fascinated with human psychology and wanted to become a psychiatrist. In medical school, I got to observe some of the first endovascular stent grafts for abdominal aortic aneurysm (AAA) by one of their pioneers, Konstantinos Papazoglou—I am not sure if I was impressed by the nature of the interventions or by simply watching someone who is far better than his average colleagues, but it definitely impacted my decision to choose vascular surgery as a speciality. My interest in vascular access probably coincided with me working alongside Myriam Combes in Paris and, later, with William “Tip” Jennings in Tulsa.

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

I was really blessed and lucky to meet and work with people like Roy Greenberg, Jean-Pierre Becquemin, Martin Malina, Thomas Fogarty and Edward Diethrich. These extremely gifted people can positively affect someone’s life with a simple word or piece of advice. I will never forget October 2021 – Issue 1

when, after a presentation I gave as a recipient of Edward Diethrich’s scholarship, he came to me and simply said: “Well done, I am proud of you.”

It was one of the most important moments of my life. He was like a rockstar from another planet— not only as a doctor and surgeon, but as a person too. Besides these very special people, I developed a relationship of mentorship and friendship with three people: Konstantinos Papazoglou, Benoit Boura and Tip Jennings. They were all there for me in different moments of my life to support and advise me, and I will always remain particularly grateful.

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

Indisputably, the percutaneous creation of arteriovenous fistulas (AVFs) is the most important development in vascular access and one of the most important in vascular surgery too.

It is transformational in ways that will become obvious 10–15 years from now. People will look back on pictures of huge aneurysmal fistulas and find it difficult to believe this was acceptable in medicine. It made vascular access surgeons think

about anatomy and physiology in a totally different and unconventional way, and patient preferences for this new technology have meant there is little space for laggers to resist these changes.

EndoAVFs are a relatively new concept. How do the two main systems stack up against each other in terms of creation, and maintenance in the long term?

Both systems are similar as they create a communication in a location where a vein lies next to the artery, and then rely on the perforator to bring this blood up into the superficial system and enable its use for dialysis. However, they are different in terms of energy used and exact location. Ellipsys most likely needs better ultrasound skills for the puncture, while WavelinQ (BD) probably has different challenges as the connection is in a location that is a bit more variable and distant than the precious perforator vein. Both systems and the companies that have acquired them serve the promise for medical innovation and better patient care very well.

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

I think new data that came out from a recent randomised controlled trial in the New England Journal of Medicine (NEJM) on drug-coated balloons (DCBs) in vascular access are very promising, and they have relieved our anxiety about mortality issues and highlighted a potential for fewer interventions. Covered stents can also be promising in some locations in order to completely cover the diseased segments. While AVFs are preferred, we need to be aware that a diseased vein cannot provide a good-quality AVF, and we should not hesitate to use newer technologies if they can improve the patient’s quality of life and survival chances—which is essentially what we do when we provide reliable access for dialysis.

What is the most significant unmet need in the field right now?

I think the Achilles’ heel is still the fact multiple reinterventions are required for the majority of patients. We need to reach a point where we will be able to say to most patients that multiple reinterventions will be exceptional, and not the rule.

What are you seeking to achieve with the vascular access component of the Paris Vascular Insights meeting?

Together with Yann Gouëffic, Stéphan Haulon, and the other organisers of PVI, I would like to strengthen it and establish it as one of the top five, or even top three, vascular meetings in the world. This year, we have a new venue, and a total remake of the style and overall organisation of the event. The same goes for the access session—I want it to be one of the meetings that specialists from all over the world will not want to miss each year as an opportunity to learn and have fun together.

How did your period in military service influence you as a physician?

From the moment we enter medical school, we become fairly confined in terms of our social interactions and interests—all our friends are doctors and all of our discussions are around medicine. At the age of 31, I started my military service much older than the other cadets. I was very stressed, and worried about how I would

Fact file Current appointments: Vascular surgeon and director, Vascular Access Center, Hôpital Paris Saint-Joseph, Paris, France Chief of vascular surgery, Centre Hospitalier de Chartres, Le Coudray, France

Education: 2001: MD, Aristotle University, Thessaloniki, Greece 2003–06: General surgery resident, Thessaloniki, Greece 2007–08: Military service, Greece 2008–12: Vascular surgery resident, Paris, France 2012–14: Vascular surgery fellow, Tulsa, USA

Honours (selected): 2010: International Travelling Fellow Grant, Edward B Diethrich Vascular Surgical Society, Scottsdale, USA 2010: Best Poster Presentation, European Society for Vascular Surgery (ESVS) Annual Conference, Amsterdam, The Netherlands 2020: Pioneering pAVF creation efforts with Ellipsys system published in Journal of Vascular Surgery (JVS) Conference director, International Vascular Access Symposium and PVI, Paris, France

Illustration by: Andy Watt / NB Illustration

Profile

cope with people giving me orders, but it ended up being one of the best and more relaxed periods of my life. I got to interact with soldiers from all possible backgrounds and cultures. I was like an older brother for the ones that were a bit more fragile and sensible. I made some good friends, and one great one—general Christos Drivas— who later became the godfather of my youngest daughter.

You have previously taken part in humanitarian missions in Jamaica and Guatemala.

What were your experiences and takeaways from practising in these surgically austere environments?

Those mission trips are definitely a life-changing experience, and they provide a stress test for your technical and social skills. For one week, you are an “invited invader” of a local system, and you have to do the maximum amount of good and zero harm, if possible. While there are some excellent local colleagues that act as coordinators and make things easier—and patients and families are grateful for your service—the rest of the hospital, the rest of the country, even, are not necessarily fond of you being there. Access

“We need to reach a point where we can say to most patients that multiple reinterventions will be exceptional, and not the rule.” to resources and overall support is limited, there are many patients waiting on you as a messiah to perform their surgery, and there is also no one to fix complications after you leave. It is a very unique cocktail of factors!

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

The same advice I would give to anyone for any

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profession: make sure you love it and you are having fun when you are doing it. I am lucky because I am having fun in the operating room.

No matter how tired I am when I operate, I am enjoying it, which makes everything much easier.

What are your interests outside of the field of medicine?

I love sailing and swimming with my daughters, and I will do this a lot more as they get older.

I enjoy riding my motorcycle whenever I find time and the French weather allows. I also enjoy reading about politics and the global economy, and, although I am still a rookie, I do a bit of day trading—including lots of emotional trades that make me lose in five minutes what I have made in one week! It is very frustrating but there is a certain process of mastering yourself, and your actions and emotions, that I find to be a very interesting personal challenge. At this stage, I am still like a first-year resident with a scalpel in his hand—not very trustworthy. But, who knows, I may get good at it one day and be able to operate only for fun, during missions, and to train young surgeons.

Issue 1 – October 2021

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Novel Technologies

A first look at the vibrant landscape of vascular access care in 2025 The field of vascular access care for haemodialysis patients may look very different in just a few years’ time, with a host of new, innovative technologies currently being developed and tested to help tackle existing challenges relating to infection, the long-term patency of blood vessels, and complications arising from poor needle cannulation. A session from this year’s Vascular Access Society of the Americas 2021 Spring Virtual Conference (VASA, 21–22 May, online) saw nitric oxide (NO)-releasing devices, state-of-the-art optic sensors and bioengineered “living” arteriovenous grafts (AVGs) presented to the audience.

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nterventional nephrologist Karthik Ramani (University of Michigan, Ann Arbor, USA) kicked off the VASA 2021 session, entitled ‘What will vascular access care look like in 2025?’, by presenting a new approach to infection control for haemodialysis catheters: NO rechargeable fillers. Haemodialysis catheters, he claimed, are associated with “a great deal of morbidity and mortality, as well as a tremendous cost to the healthcare system”, with these issues often stemming from either catheter-related bloodstream infection, or inflammation whereby platelet activation leads to thrombosis in the blood vessel.

The solution Ramani presented is NitriCap (NitriCap Medical)—a single-use, antimicrobial catheter insert device that provides “superior protection” from bloodstream infections via the timed, controlled release of NO. As well as stating that NitriCap “overcomes many shortcomings of antibiotics in treating catheter-related bacteraemia”, Ramani outlined two in vivo real-world studies involving sheep that have assessed NitriCap versus a competitor product that uses a different antimicrobial, chlorhexidine, to reduce infections, and a standard haemodialysis catheter cap. He reported a 10,000-fold reduction in colony-forming units (CFUs) associated with NitriCap in both studies, and “superior antimicrobial efficacy” in all four regions of the catheter compared to both the standard cap and the competitor product.

In addition to the initial target area of tunnelled haemodialysis catheters, Ramani claimed that NO could subsequently be used in other spaces including temporary haemodialysis, peritoneal dialysis, and central venous catheters (CVCs), in the future, closing his presentation by quipping that “the future is definitely NOw”.

Dealing with the foreign body reaction The following presentation saw bioengineer Buddy Ratner (University of Washington, Seattle, USA) exhibit a novel method for reducing the formation of fibrosis that is often observed in synthetic vascular grafts following implantation—something that ultimately reduces graft compliance and long-term functionality. This contributes to AVGs having a 50% failure rate at one year, and therefore requiring routine October 2021 – Issue 1

maintenance, he added. Ratner’s answer to this is a patented, bioengineered material dubbed ‘6S’, which can mitigate the foreign body reaction to an implanted graft and allow blood vessel ingrowth thanks to its precision-porous structure.

The material has been used by Ratner and his colleagues at the Center for Dialysis Innovation (CDI) to develop a vascular prosthesis, with comparisons between this 6S prosthesis and a standard polytetrafluoroethylene (PTFE) graft in an animal model resulting in the former looking like a “living artery” that was “pulsating nicely” when opened up at one month, according to Ratner, while a dense fibrotic capsule formed around the latter. He concluded that, regarding observations in these tests and others, “this is all looking very promising for a new mode of healing for synthetic grafts”, adding that the 6S biomaterial not only addresses inflammation, but also issues surrounding long-term durability, costs and regulatory hurdles that have plagued existing graft products for several decades. Ratner added that the 6S graft is now being examined further in sheep and pig models.

On a similar note, biomedical engineer Aijun Wang (UC Davis, Davis, USA) presented his own efforts as part of VasoBio—a company spun out of UC Davis and co-founded by Wang himself— to engineer a self-renewable, ‘living’ surface for vascular grafts, improving their in situ endothelialisation and, ultimately, their long-term patency when used for haemodialysis. To this end, the ‘LXW7’ ligand, which holds a high affinity and specificity for endothelial progenitor cells and endothelial cells, was developed.

Wang asserted that, when compared to an untreated vascular graft surface, the surface of the LXW7-coated graft has demonstrated an increase in endothelium coverage within three days. He added that LXW7 was observed to have improved graft patency during a carotid artery bypass in a rat model and that, when progressed into a larger pig model, the luminal surface of an LXW7-coated graft was free from blood clotting and had a smoother surface compared to an untreated graft four weeks after implantation.

Innovations in frontline care Another presentation saw David Kuraguntla (San Francisco, USA), founder and CEO of Alio Medical, discuss the need to combat the “significant healthcare burden” of kidney failure. Kuraguntla suggested bringing remote monitoring to the field of vascular access care may be the answer, presenting the results of a study assessing his company’s SmartPatch product—a wearable, 24/7 monitoring device that uses state-of-the-art optical sensor technology to measure volumetric flow rate, percentage stenosis and haemoglobin levels. Raw data from the SmartPatch are then processed in the cloud and analysed using machine learning, subsequently presenting these well-known, clinically actionable biometrics to a physician.

The study Kuraguntla discussed involved 128 haemodialysis patients across three centres, all of

David Kuraguntla

Karthik Ramani

Buddy Ratner

“There is clear evidence that—if we want to move the needle— there has to be cooperation between engineering and medicine.”

Prabir RoyChaudhury

whom wore the device over their arteriovenous fistula—either in their upper or lower arm—for one week. He reported that the SmartPatch system measured haemoglobin with comparable or better accuracy and precision compared to available methods, detected low flow rates with 100% sensitivity and 75% specificity, and showed zero false positives and 100% sensitivity in detecting haemodynamically significant stenosis (>50%). In addition to concluding the study therefore demonstrates the SmartPatch’s round-the-clock monitoring capabilities, Kuraguntla concluded that, more generally, “remote monitoring systems show potential promise in improving the care and lowering the costs associated with dialysis access”.

Bioengineer Joseph Singapogu (Clemson University, Clemson, USA) closed the session by presenting his attempts to tackle the various issues stemming from poor needle cannulation—asserting that there is a direct link between cannulation outcomes and the skill of the clinician who is cannulating, but, despite this, cannulation training today is limited and relies on outdated tools. He noted that simulator technologies could help to improve this state of affairs, as they allow for safer practice in a non-clinical setting, create objective metrics for assessing skill levels, and can provide personalised feedback to improve these skill levels.

Singapogu went on to present his state-of-theart simulator for haemodialysis cannulation, which consists of a layer of artificial skin and a range of sensors to measure several parameters including pinch forces, needle motion and angle, time taken to cannulate, and even palpation technique prior to inserting the needle. The main goal behind the novel simulator, he said, is to provide a standardised way of measuring cannulation skill, as its metrics-driven nature helps to minimise subjectivity, before concluding that he believes the future of cannulation skills training will be simulator-based.

Individualised care key in future A discussion following this session saw one of the moderators, nephrologist and co-director at UNC Kidney Center Prabir Roy-Chaudhury (University of North Carolina, Chapel Hill, USA), reflect that “there was clear evidence that—if we want to move the needle—there has to be cooperation and collaboration between engineering and medicine” before posing a question to the panel over what would be more suitable: a one-size-fitsall approach to vascular access technologies, or a pathway of individualisation, whereby specific patient populations are identified and targeted.

The consensus among the panel was that the latter will be more appropriate in maximising the potential of these innovations, with Ramani stating that he hopes NitriCap and other technologies presented at VASA 2021 will serve a large population—but that, ultimately, “we still have to personalise our care” and it will “definitely not be a one-size-fits-all approach”. On a similar note, Ratner added that he and his colleagues at the CDI believe “patient feedback is absolutely critical to developing new products, and people want things customised to their own specific needs”.

Following a discussion instigated by the session’s other moderator, vascular and interventional radiologist Sanjay Misra (Mayo Clinic, Rochester, USA), Roy-Chaudhury discussed the topics of funding and regulation in this space.

While he did agree with the other panellists on the importance of philanthropy and angel investors, as well as venture capital and non-typical federal funding, Roy-Chaudhury opted to end this part of the discussion on a positive note, stating that “through organisations like the Kidney Health Initiative, there is now more partnership with the US FDA [Food and Drug Administration]—who have been huge supporters of many of the things we have been speaking about”. In closing the session, he added: “I hope that things are changing with more awareness in federal agencies, and in the community as a whole.”

Drug-Coated Balloons

Drug-coated balloons favoured over angioplasty in treating dysfunctional haemodialysis access A patient-level meta-analysis of randomised controlled trials (RCTs) has shown that drug-coated balloons (DCBs) were “consistently favoured” over percutaneous transluminal angioplasty (PTA) to prolong target lesion primary patency and access circuit primary patency in the treatment of dysfunctional haemodialysis venous access. The research, authored by Khi Yung Fong, Joseph Zhao (both National University of Singapore, Singapore), Chow Wei Too (SingHealth Duke-NUS Academic Medical Centre, Singapore), and colleagues, was recently published online in the European Journal of Vascular and Endovascular Surgery (EJVES).

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his is the first patient-level, RCT-only meta-analysis comparing DCB with PTA in haemodialysis access restenosis, the

authors claim. They detail that a total of 11 RCTs, comprising 1,347 patients, were included in their analysis. Fong, Zhao, Too et al add that two of the studies analysed were published as recently as 2020.

The authors report that, among 10 RCTs (1,207 patients), hazard ratios (HRs) across all models favoured DCB (one-stage shared frailty HR 0.62, 95% confidence interval [CI] 0.53–0.73, p<0.001); two-stage random effects HR 0.6, 95% CI 0.42– 0.86, p=0.018, I2=65%) for target lesion primary patency.

In addition, they found that target lesion primary patency restricted mean survival times were +3.54 months (25%) longer in patients who received DCB treatment compared with PTA (p=0.001) at three years. Target lesion primary patency at six months, one year, and two years was 75.3% vs. 58.1%, 51.1% vs. 37.1%, and 31.4% vs.

26% for DCB and PTA, respectively, Fong, Zhao,

Target lesion primary patency rates:

DCB =

75.3% at six months

51.1% at one year

31.4% at two years

PTA =

58.1% at six months

37.1% at one year

26% at two years

IN.PACT AV DCB sustained “superior” effectiveness in subgroups with high reintervention rates out to two years

Robert Lookstein

Several subgroups of patients treated with the IN.PACT AV drug-coated balloon (DCB; Medtronic) for arteriovenous fistulas (AVFs) demonstrated a “statistically significant” higher rate of target lesion primary patency (TLPP) compared to those who underwent standard percutaneous transluminal angioplasty (PTA) through 24 months, investigators behind the IN.PACT AV Access study have reported.

PRINCIPAL INVESTIGATOR ROBERT LOOKSTEIN, executive vice chair in the Department of Diagnostic, Molecular and Interventional Radiology at Mount Sinai Health System in New York, USA, delivered the two-year results from the trial during a late-breaking session at this year’s Vascular InterVentional Advances conference (VIVA; 4–7 October 2021, Las Vegas, USA).

IN.PACT AV is a prospective, global, single-blinded, randomised controlled trial with 330 participants, in which 170 patients received IN.PACT AV DCB and 160 underwent PTA. The investigators reported that the

primary outcome of TLPP—defined as freedom from clinically driven target lesion revascularisation—in patients with restenotic lesions, radiocephalic and brachiocephalic AVF types, cannulation zone lesions as well as anastomotic lesions treated with the DCB through 24 months was superior to those who received PTA treatment in all cases.“Benefits were seen in all other subgroups, though sample sizes were small and the treatment effect was not statistically significant,” Lookstein told VIVA attendees.

The results showed higher TLPP with DCB vs PTA based on time-to-event analyses: restenotic lesions (46%

15

Too, and colleagues relay.

An “intriguing” finding relates to paclitaxel dose, the authors detail, noting that the p scores within a Frequentist network meta-analysis suggest higher concentrations of paclitaxel were associated with better target lesion primary patency and access circuit primary patency.

The authors further report that, among six RCTs (854 patients), a one-stage model favoured DCB (shared frailty HR 0.72, 95% CI 0.6–0.87, p<0.001) for access circuit primary patency.

However, they add, a two-stage random effects model demonstrated no significant difference (HR 0.76, 95% CI 0.35–1.67, p=0.41, I2=81%).

Notwithstanding, the investigators relay that sensitivity analysis for access circuit primary patency excluding outliers significantly favoured DCB (HR 0.61, 95% CI 0.41–0.91, p=0.027, I2=62%).

Detailing certain limitations of their research, Fong, Zhao, Too et al acknowledge that their analyses were unable to account for competing risks to restenosis, such as patient mortality, for which previous studies yielded mixed findings.

In addition, they stress that clinical judgement to proceed with either DCB or PTA should be considered alongside the side-effects of paclitaxel, effectiveness of prior PTA, procedure-related morbidity, and cost-benefit analysis, which were “beyond the scope of the present article”.

In concluding, the authors write that their research “represents a statistically robust and up-to-date comparison between DCBs and PTA”.

Looking ahead, they suggest that future investigations should focus on dose-efficacy relationships and explore how lesion-specific covariates, such as age, length, location, type, and balloon diameter may affect DCB versus PTA outcomes for haemodialysis access restenosis.

vs 30.2%), radiocephalic AVFs (53.6% vs 43%), brachiocephalic AVFs (48.5% vs 27.3%), anastomotic lesions (48.4% vs 32.7%), and lesions in the cannulation zone (74.2% vs 18.9%). The greatest TLPP benefit through 24 months was observed in “lesions treated with the smallest balloon diameter sizes”—those treated with balloon diameters of >6mm showed a TLPP of 52.2% in the case of the DCB group vs 38.9% among PTA patients. Meanwhile, lesions tackled using balloons with diameters ≤6mm saw TLPP rates of 52.1% (DCB) vs 32.6% (PTA), the data showed.

“I think this really starts to identify the specific patient population and lesions that are ideally suited for this technology,” Lookstein said. “These durable, long-term data suggest the use of this therapy may be considered standard-of-care for patients with end-stage renal disease [ESRD] at high risk for repeat interventions in their arteriovenous fistulas.”

Session moderator Ehrin Armstrong (Adventist Health, St Helena, USA) asked Lookstein to comment on the finding showing patency was similar with DCBs “regardless of size”. He responded: “There has been some speculation as to why the benefit was so pronounced, why we were able to demonstrate such superior clinical benefit of this technology, and I think we are starting to identify perhaps that, because we were able to enrol 50% radiocephalic lesions in the forearm, and we saw the greatest benefit in the smallest balloon diameter sizes, that may be where patients derive the most significant benefit. Again, the benefit was seen across the entire anatomic spectrum, but clearly we are identifying a subset where there is the greatest clinical benefit of sustained patency at 24 months.”

Lookstein added that the opportunity now beckons for the device to be studied prospectively for balloon maturation procedures.

“I think this really starts to identify the specific patient population and lesions that are ideally suited for this technology.”

Robert Lookstein Issue 1 – October 2021

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Research and Innovation

17

Dialysis

Improved understanding of current dialysis modalities may hold greater value than technological advances There are several different types of dialysis treatment available to kidney disease patients—with the three major players, in-centre haemodialysis (ICHD), home haemodialysis (HHD) and peritoneal dialysis (PD) all holding their own benefits and drawbacks. Mark Lambie, a senior reader and consultant in renal medicine at Keele University/Royal Stoke University Hospital in Stoke-on-Trent, UK, discusses each in greater detail and assesses the wider landscape of dialysis care.

What is the current state of play between the different types of dialysis?

Firstly, we do not tend to think of it as a competitive thing—they are different therapies with different pros and cons, and almost all modality selection is now being done via shared decision-making involving the patient. For a patient who is young, fit and healthy, and has got a job, a home dialysis modality will probably be easier than an in-centre regime. And, HHD is more likely to be used by patients who have had a previous transplant, or have been on dialysis before, while PD is often used at an earlier stage, as it is more suited to patients with some residual kidney function.

Ultimately, discussions about any of these being considered as the standard of care are difficult, because it is almost impossible to compare them. This is partly down to the fact nobody will ever be able to do a randomised controlled trial in this area, so we will never know, definitively, how they compare, but it is also because outcomes for each modality are context-dependent. Death rates in PD have fallen continuously since the 1990s in the USA—an example highlighting that any comparisons we could make are specific to the time, place or healthcare system in question, as opposed to being intrinsic to the modality itself.

What are the pros and cons of in-centre and at-home dialysis options?

There is definitely a significant proportion of the population for whom ICHD is the best option—it removes much of the burden on the patient of managing their own treatment and, if you are old and frail, and at risk of becoming isolated, leaving your house regularly for a social environment where you can talk to nurses and other patients holds no small value. On the other hand, ICHD, at least in the UK, tends to be pretty inflexible, as patients have to undergo four hours of treatment, on three different days, each week, and they have no control over when those slots are. The other big downside is travel. For many patients, transportation to the centre involves long waits and uncertainty over what time they are going to be picked up or dropped off. This is by far the most common thing patients complain about.

PD and HHD have the same major advantage, which is that they can be done at home, giving the patient more autonomy and flexibility regarding their treatment regime. PD is also a continuous

therapy, for the most part, meaning the intensity of the treatment is reduced—as are the fatigue and cardiovascular side-effects that come with regular dialysis sessions—while HHD has the potential to achieve massively greater fluid clearance in patients who have lost their residual renal function. Peritonitis is a significant downside to PD, although it is balanced to some extent by the infection risk of septicaemia in haemodialysis. There is also a storage problem associated with home dialysis modalities, because the amount of dialysate required takes up a lot of space in the patient’s home, and the ongoing responsibility of managing your own treatment, for both PD and HHD, can lead to a sense of burnout over time.

How do you assess the feasibility of a hybrid approach that incorporates the two?

I think it is technically achievable, but the challenges here are less medical and more patient-related, or healthcare expenditure-related. The only country that currently practices that joint model is Japan—whereby, if patients on PD are encountering problems relating to solute or water clearance, they will often be switched to the hybrid therapy to undergo one haemodialysis per week alongside PD. No other country really does that right now, and that is mainly driven by concerns around what you are asking the patient to do by exposing them to the

added responsibility, and downsides, of both approaches. The fact healthcare providers will also have to fund both modalities simultaneously makes it very costly as well. We have known for quite a long time that this hybrid approach is an option—and, purely in terms of clinical outcomes, it is going to give the patient more control and improved clearance— but increased expense and treatment burden have prevented physicians and patients alike from embracing it to date.

Do you think new technologies are likely to change the current landscape in dialysis care?

There have been attempts to innovate and improve each of these modalities, and these attempts have been going on for some time. Hopefully one of them will come good—but, as yet, none have. There are concepts for enabling continuous haemodialysis using a wearable device and there are sorbent technology-based artificial kidneys designed to enhance clearance with PD as well. While these technologies look very good on paper, there are still some major technical challenges to overcome, and more proof is needed that they can demonstrate sufficient real-world advantages compared to existing options, with no additional downsides, to justify their use.

One thing I am personally more interested in right now is the possibility of manufacturing dialysate onsite, as this

Mark Lambie

could help to overcome the storage problem associated with PD especially.

While it appears to be technically possible to develop dialysis machines that can manufacture dialysate themselves, the commercial incentives of the companies that make their money selling dialysate present a challenge we will have to navigate. Recently, the most exciting development in haemodialysis has been the introduction of HHD machines that are smaller, more portable and easier to use for patients. Examples of these include the SC+ device (Quanta Dialysis Technologies), the Tablo machine (Outset Medical) and the NxStage system (Fresenius Medical Care). Each comes with its own pros, cons and unique features but, overall, the hope is that they will all facilitate a greater uptake of HHD and enhance the existing benefits associated with this modality.

“I believe that, for the most part, people have moved away from thinking that increased benefits from dialysis are going to be driven by the next gadget or technical tool.”

Where should the focus be for future research relating to dialysis?

One of the bigger issues at the moment is to do with healthcare, and how it is delivered. We know there is huge variability internationally in how these different modalities are deployed—and we know that, even within the UK, there is huge variability between centres as well. I am a co-investigator for the ongoing InterCEPt study, which is specifically designed to find out what is driving these UK-wide differences, particularly in home dialysis usage. We will have to wait for the results of this study, of course, but my own personal belief is that these discrepancies are likely to reflect the cultures and attitudes within different units—and how strongly the senior clinicians within these units believe in the benefits of home dialysis modalities. And, following on from this study, one of the main things we need to be focusing on is reducing this unwarranted variation by supporting the centres where home dialysis usage is lower and, ultimately, helping them to increase rates of HHD and PD compared to ICHD. Expanding this outside of the UK, I think all countries need to be looking at how their long-term interests relate to dialysis service because, in developed countries at least, it will be cheaper for them to use PD more widely, meaning they need to think about how they are incentivising home dialysis usage. I believe that, for the most part, people have moved away from thinking that increased benefits from dialysis are going to be driven by the next gadget or technical tool. The focus is more likely to be on better understanding what we have already got and trying to improve patient outcomes that way.

Issue 1 – October 2021

18

Home Dialysis Debates

Dialysis

Turning the dial to ensure equitable access to home dialysis There are multiple barriers to home dialysis initiation, and these disproportionately affect vulnerable populations. Current solutions need to be scaled up, with particular emphasis on educating physicians on home dialysis, improving modality education, increasing support for patients and families, and changing financial incentives to favour building home dialysis programmes. There is also a need to better understand culturally specific barriers to home dialysis choice. This was the crux of a presentation by Jenny Shen (Division of Nephrology and Hypertension, David Geffen School of Medicine at University of California, Los Angeles, USA) on ensuring equitable access to home dialysis at the UK Kidney Week virtual conference (UKKW; 4–7 October 2021).

A

roundtable discussion following the session on improving access to UK home dialysis was chaired

by Simon Davies (University Hospital of North Midlands, Stoke-on-Trent, UK) with participation from session chairs and fellow consultant nephrologists Jyoti Baharani (Heartlands Hospital, part of University Hospitals NHS Trust, Birmingham, UK) and Bhrigu Sood (St Helier Hospital, Epsom, UK), as well as Kirit Modi (honorary president of the National Kidney Federation [NKF], London, UK), Anna Winterbottom (decision scientist at University of Leeds, Leeds, UK) and Sandip Mitra (consultant nephrologist at Manchester University Hospitals Foundation Trust, Manchester, UK).

Davies kickstarted the conversation by asking the panel to pinpoint the single most impactful intervention on equity of access to home dialysis. Modi responded by

From top: Jyoti Baharani, Simon Davies, Kirit Modi, Jenny Shen and Anna Winterbottom

stressing that the federation had been campaigning for more home dialysis for several years. He emphasised systemic and structural issues prevented patients from accessing home dialysis, noting that the issue of equity nested within that larger framework.

In January 2021, the UK NKF published a report urging the kidney community to step up and increase home dialysis provision. It makes seven recommendations, and the charity also wants all adults in the UK to reach a minimum prevalence rate of 20% of their dialysis population on home dialysis by the end of 2024. “We need to look at policies and practices at the highest levels, because I do not think that units providing [in-centre] dialysis are sufficiently accountable for what they do,” Modi said. “And, therefore, nobody questions and challenges them, because the data has been there for a long time.”

With regard to the levers for change, he set his sights on improving the support for patients considering dialysis modalities. “Many patients do not know enough about home dialysis and its benefits, and can be worried about taking on extra responsibility. That is where the NKF is increasing the range of support it provides to home dialysis patients.”

In September 2021, the NKF established a peer support service for home dialysis patients and carers, giving them the opportunity to talk in confidence to those with first-hand experience of home dialysis. “We are hoping that will help patients up and down the country so they are empowered to ask the question locally—to say, can I please be considered [for home dialysis]?” he outlined.

Winterbottom zeroed in on the need to present consistent information that informs people about all available treatments in an equitable way. Her go-to single intervention would see the integration of patient decision aids within kidney services, to improve the quality and consistency of patient information.

Significant mortality increase seen after home haemodialysis failure compared to continued treatment Failure of home haemodialysis (HHD) treatment, defined as a return to in-centre haemodialysis (ICHD), has been associated with a “significant increase” in mortality when compared to continued HHD—a trend that was observed in both the early (first 30 days and 30–90 days) and late (>90 days) periods following treatment failure. This is according to data published in the American Journal of Kidney Diseases (AJKD).

IN REPORTING THEIR RESULTS, LEAD AUTHOR David Semple (Auckland District Health Board, Auckland, New Zealand) and colleagues also note: “In this study, we wanted to understand what happens after a person moves from HHD to ICHD by comparing the rate of death as patients moved between treatments. We found that the risk of death is high following the transition and remains high after three months. We could not

October 2021 – Issue 1

discern the cause of this association, but suspect it is due to the events that caused patients to stop HHD. The group of patients who stopped haemodialysis only for a period of time did not have an elevated rate of death—we suspect this is because they did not transiently stop HHD due to serious illness.”

The researchers’ retrospective, multicentre, largescale cohort study included a total of 19,306 patients represented in the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry who commenced haemodialysis between January 2005 and December 2015, and were treated for more than 90 days. The primary outcome of the study was all-cause mortality.

The authors note that, among the 6,972 patients that died at follow-up, the crude death rate was highest in ICHD patients with no prior HHD (14.9 per 100 patient years) and ICHD patients with prior HHD (14.4 per 100 patient years), and lowest in patients in their first HHD episode

“We know there is a wide variation of how pretreatment education is provided in terms of the type and amount of information that people receive,” she added. “There are multiple patient leaflets available, developed by different organisations, and not all of them are designed in ways that are known to promote informed decision-making.

Patient decision aids can help reduce some of that potential bias and help people understand their treatment options in the context of their care pathway, and their daily lives.”

Prompted by Davies to describe measures that had successfully resulted in an upswing in home dialysis uptake at her centre, Baharani provided insight into galvanising a culture change for patients and staff. “We did that by overhauling the way we spoke to patients,” she said. “We made some simple tweaks ensuring that patients had to come to peritoneal dialysis to meet the nurses, whereas before they only had to go into a haemodialysis unit, and we introduced peer educators. I am

“With in-centre haemodialysis, there is always room at the inn.

It makes us lazy as clinicians, because it is the default therapy.”

Jyoti Baharani also going to say something controversial: with in-centre haemodialysis, there is always room at the inn. It makes us lazy as clinicians, because it is the default therapy.”

Echoing Baharani’s emphasis on the importance of peer education, Mitra then alluded to national registry and unit data suggesting that most patients who begin on in-centre haemodialysis find it “very difficult to transition out of that”. This has accelerated efforts on predialysis education. “[However], the vast majority of our patients are already on haemodialysis, and the nurses who interact with the patients have usually had a negative experience derived from patients who come to them after complications from home therapy. So, if I had to choose one intervention to improve the conversation, it would be to get satellite haemodialysis unit nurses to come in and work in home therapy centres, with the home therapy teams, to see the good aspect of home therapy care, and then create that conversation in our dialysis units that will enable a transition to home therapies,” he concluded.

(4.4 per 100 patient years) and patients with HHD, and prior ICHD and HHD (5.9 per 100 patient years).

They add that the mortality rate in ICHD patients with prior HHD was 20.6 per 100 patient years during the first 30 days, 17.5 per 100 patient years at 30–90 days, and 13.6 per 100 patient years beyond 90 days, meaning that— across all three of these timeframes—univariate and multivariate analysis showed a transition from HHD to ICHD (HHD treatment failure) was associated with an increased risk of death. While other significant independent covariates for death were also identified, only patient age was associated with a “similar magnitude” of mortality risk to HHD treatment failure. Withdrawal from treatment and cardiovascular events were the most common causes of death, the study found.

The authors also note that their “key novel finding” of HHD treatment failure being associated with a significantly increased risk of early and late death may be “less vulnerable to the residual confounding inherent in a registry study of this type”, due to all patients restarting ICHD after a period of HHD having, at one stage, the clinical and socioeconomic attributes enabling a successful initiation of HHD. They add that, while no conclusions on the underlying mechanism for this increased risk of death can be drawn, it “represents an important finding that should stimulate additional investigation”.

Patient Outcomes

19

Dialysis First International Home Dialysis Roundtable issues action agenda to redouble efforts on broad scale home dialysis use Catalysed by the COVID-19 pandemic, leading global kidney disease organisations converged late in 2020 at the first International Home Dialysis Roundtable (IHDR) to focus on strategies to urgently increase access to and uptake of both home haemodialysis (HHD) and peritoneal dialysis (PD). A follow-up meeting is planned for the last quarter of this year to track progress on enabling a “wholesale shift in clinical culture to reshuffle the current philosophy of prioritising treatment options, moving from a system that directs most patients to in-centre dialysis to one that more broadly recognises and supports home dialysis as a viable first-choice option for patients”.

THE ROUNDTABLE, DESCRIBED AS “GROUND breaking”, identified strategies to truly involve patients in their own care and reduce the barriers to home dialysis including tackling paternalistic attitudes among healthcare workers, creating a culture of support for home dialysis, fostering patient and clinician champions, such as nurses, as advocates, and—vitally—joining forces to develop internationally shareable best practices.

While dialysis started as a largely home-based treatment in the 1960s with HHD, a clear shift over the intervening decades propelled centre-based dialysis into becoming the dominant renal replacement therapy internationally. In 2011, Martin Wilkie (Sheffield, UK) wrote in NDT Plus that only nine of 36 countries (Canada, The Netherlands, Iceland, Finland, Denmark, Australia, New Zealand, Mexico, and Hong Kong) report home dialysis for more than 20% of prevalent dialysis patients.

Now, augmented by research demonstrating that home dialysis has significant economic, quality-of-life, and clinical advantages when compared with in-centre dialysis, parallel developments of novel HHD machines, and progress in continuous ambulatory or automated PD that enable at-home treatment, form the bedrock of an ecosystem capable of driving a resurgence in home dialysis. But this resurgence relies on a multipronged strategy to improved home dialysis uptake.

Mallika Mendu (Brigham and Women’s Hospital, Boston, USA) and colleagues report in Kidney Medicine in July–August 2021 that the IHDR participants identified four domains of action opportunities to support and elevate home dialysis initiatives worldwide. These are: establishment of international standards to increase home dialysis; empowerment of patients, improved shared decision-making and reduction of paternalism among healthcare providers; creation of a “culture of support” for home dialysis among healthcare providers through education and training; and creation of internationally shareable best practices on strategies to reduce institutional roadblocks to home dialysis.

In addition to committing to advancing best practice, participating organisations pledged to equip colleagues in disparate regions, “find and develop home dialysis patient and clinician ‘champions’ and advocate for pro-home dialysis policy change in their respective regions”. Mendu and colleagues also write: “Two major practical barriers to home dialysis use include vascular or peritoneal catheter placement and payment disparity (between in-centre and home dialysis modalities), which are largely institutional or governmental in origin.”

Further, they conclude: “There was broad consensus that the action recommendations be shared with government policy regulators and administrators, as policy changes are needed to affect home dialysis uptake around the world. The IHDR participants agreed that the kidney community must use the enthusiasm from the roundtable discussion and the momentum created by the pandemic to support and elevate home dialysis initiatives worldwide.”

Nationwide survey indicates hesitancy among US dialysis patient groups over COVID-19 vaccination A nationwide survey distributed among 150 randomly selected dialysis facilities in the USA has found that a “substantial proportion” of patients receiving in-centre haemodialysis are hesitant about seeking a COVID-19 vaccination. Notably, this proportion is still thought to be close to half of that seen across the general US population.

The findings of this report, which are published in the Journal of the American Society of Nephrology ( JASN), also indicate that the odds of vaccine hesitancy are higher among younger patients, women, and Black, Native American and Pacific Islander patients.

“O

ur results highlight opportunities for improving SARS-CoV-2 vaccine uptake through dialysis facilities,” Pablo Garcia, Shuchi Anand (Department of Medicine [Nephrology], Stanford University, Stanford, USA) and colleagues write in their report. “On the basis of these survey results, we would advise dialysis organisations and patient advocacy groups to focus vaccine promotion efforts among younger age groups, women, and Black, Native American, and Pacific Islander patients, and to develop patient-friendly educational material describing the rates and nature of vaccine-related adverse effects.

“The caveats that side-effects and efficacy have not been specifically evaluated in patients on dialysis complicate outreach efforts. Dialysis care providers and public health agencies should capture data on safety (adverse effects) and provisional efficacy (seroconversion) in the dialysis population, and rapidly disseminate these data to facilitate vaccine uptake.”

In an effort to inform programmes and policies aimed at promoting COVID-19 vaccine uptake in vulnerable dialysis patient populations, Garcia, Anand et al offered an anonymised

Shuchi Anand

online survey to patients undergoing in-centre haemodialysis in 150 randomly selected facilities, managed by US Renal Care, in early 2021.

The survey was available in English and Spanish.

A total of 1,515 patients—14% of the 10,974 patients considered eligible—responded to the survey. Some 20% of all responders were “reluctant” to seek the COVID-19 vaccine, even if it was considered safe for the general population. Younger age groups (aged 18–44 years) and Black responders were found to be more likely to indicate hesitancy, with both groups reporting hesitancy at a rate of 29%, compared to older age groups (aged 45–80 or more years) and non-Hispanic white patients, respectively. Odds of vaccine hesitancy were also higher among women compared to men, and patients categorised as “other” in terms of race or ethnicity—a

“Our results highlight opportunities for improving SARS-CoV-2 vaccine uptake through dialysis facilities.” group largely comprised of patients identifying as Native Americans or Pacific Islanders— compared to non-Hispanic white patients.

The overriding concern of patients who were vaccine hesitant related to side-effects, Garcia, Anand et al note, followed by doubts about the efficacy of the vaccine, and being uncomfortable with vaccines in general. The main sources respondents were reportedly receiving information about COVID-19 vaccines from were television news (68%), followed by dialysis staff (38%).

“Overall, vaccine hesitancy rates were nearly half that of the most recently reported rates for the general US population,” they conclude.

Pablo Garcia

Issue 1 – October 2021

20

Kidney Transplant Access

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Transplantation xxx

New recommendations signal drive to move thousands of patients from dialysis to transplantation The National Kidney Foundation (NKF) has released a position paper, developed by 16 nephrology experts from 13 institutions, with recommendations designed to navigate future research and innovation addressing the most pressing barriers to kidney transplant access, organ availability, and long-term allograft survival in the USA.

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his ambitious agenda seeks to direct research investment to optimise equity, efficiency, and patient-centred outcomes, and maximise the benefits of transplantation across the country—according to an NKF press release.

“While kidney transplantation provides the best treatment option for kidney failure to thousands of patients each year, the goal of universal access to this treatment remains elusive,” said lead author Krista Lentine (St Louis University Center for Abdominal Transplantation, St Louis, USA). “Addressing the priorities outlined in this research agenda has the potential to transform kidney patient care by expanding opportunities for safe living

donation, improving waitlist access and transplant readiness, maximising use of available deceased donor organs, and extending graft longevity.”

To assess the knowledge gaps amenable to more research, the NKF convened an expert panel to develop a research agenda aimed at advancing access to kidney transplantation for all patients who could benefit, with attention to reducing or eliminating racial and ethnic disparities, and supporting the goal of ‘one transplant for life’ for organ recipients.

“While kidney transplantation provides the best treatment option for kidney failure to thousands of patients each year, the goal of universal access to this treatment remains elusive.”

Participants, including nephrologists, surgeons, NKF leadership and patients, held a roundtable in 2019 and, through facilitated discussions, the panel developed seven priorities for research innovations along with 23 recommendations—which form the basis of the open-access paper published in the American Journal of Kidney Diseases (AJKD).

These seven key priorities are as follows: • Expand living-donor kidney transplantation • Improve management and readiness of kidney waitlists • Reduce the number of kidneys removed for transplant but never used • Increase organ acceptance using novel technology • Preserve, resuscitate, or evaluate kidney allografts before implantation • Sustain ‘one transplant for life’ • Optimise transplantation for paediatric recipients Recommended research targets are directed at key challenges within each priority, and span dimensions of educational interventions, decision science, molecular diagnostics, artificial intelligence (AI) and clinical trials.

For example, given that approximately 20% of kidneys are discarded after recovery, the authors recommend research targets including studies of patient and clinician-directed education to foster understanding of the benefits of kidneys at risk for discard, biomarkers and machine learning (ML) systems to support organ acceptance decisions, and novel preservation solutions and ex vivo interventions to preserve and resuscitate vulnerable organs before implantation.

“One of our top priorities at NKF is to make transplantation available to everyone who needs or wants a transplant,” said co-author and NKF CEO Kevin Longino.

“These recommendations will help frame our research and funding initiatives to accelerate innovation, and create the solutions we need to make transplantation a reality for all.”

Kidney transplants plummeted by 40% during first wave of COVID-19 pandemic

Asian donor and Black recipient kidney grafts associated with poorer long-term outcomes than white counterparts

The number of solid organ transplants performed during the first wave of the COVID-19 pandemic in 2020 plunged by nearly a third (31%) compared to the previous year, according to a study presented at the European Society for Organ Transplantation Congress (ESOT 2021; 29 August–1 September, Milan, Italy and virtual)—with kidney transplantation specifically showing the largest reduction (40%) across nearly all countries during 2020.

Black transplant recipients and patients who received kidneys from Asian donors had a significantly increased risk of their kidney grafts failing within seven years, according to a study presented at the European Society for Organ Transplantation Congress (ESOT 2021; 29 August–1 September, Milan, Italy and virtual).

THE RESEARCH LEVERAGED INTERNATIONAL DATA FROM 22 countries across four continents and revealed major variations in transplant programmes’ response to the pandemic, with transplant activity dropping by more than 90% in some countries. Modelling calculations suggest this slowdown led to over 48,000 years of patient life-loss.

Kidney transplantation showed the largest reduction across nearly all countries during 2020 compared to 2019, with the study finding a 40% decrease in living donor kidney transplants. For deceased kidney donor transplants, there was a 12% reduction.

The research, published in The Lancet Public Health, highlights how some countries managed to sustain their rate of transplant procedures whilst others experienced serious reductions compared to the previous year. Overall, there was a strong temporal association between increased COVID-19 infection rate, and reductions in deceased and living solid organ transplants.

The study’s lead author, Olivier Aubert (Paris Translational Research Center for Organ Transplantation, Paris, France), said: “These findings warrant further analysis on a regional, national and global level to understand why reductions did or did not occur.”

October 2021 – Issue 1

THE STUDY OF 20,304 KIDNEY organs transplanted between January 2001 and December 2015 from the UK National Health Service (NHS) Transplant Registry found Asian donor and Black recipient ethnicities were associated with inferior long-term outcomes, when compared with white counterparts.

Unadjusted survival analysis demonstrated significantly poorer long-term donor kidney outcomes associated with Asian and Black donors, compared to white donors. The seven-year graft survival was 71.9% from Asian donors, 74% from Black donors and 80.5% from white donors. And, when Cox regression analysis was used, the hazard ratio was 1.37 for Asian donors—a 37% increased risk of the

donor organ failing compared to white donors—and 1.21 for Black recipients—an increased risk of 21%.

Researchers found better human leukocyte antigen (HLA) tissue matches when the donor and recipient pairs were the same ethnicity. At seven years, 81% of white donor/recipient pairs still had a successful graft compared to 70.6% of Asian and 69.2% of Black pairs, and further analysis revealed graft survival outcomes were worse for Black recipients who received kidneys from Black donors, with a 92% increased risk of the donor organ failing compared to in white donor-white recipient pairs.

Lead study author Abdul Rahman Hakeem (St James’ University Hospital NHS Trust, Leeds, UK) stated that the disparity revealed is due to a combination of factors that put ethnic minorities at a disadvantage when it comes to transplants, with a shortage of ethnic minority donor grafts leading to ethnic minority recipients spending longer on transplant waiting lists than white counterparts. He added that, as such, efforts to expand the organ donor pool remain a “worthy goal”.

Key Research

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Transplantation

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Pilot study launched to assess third COVID-19 vaccine dose in kidney transplant recipients A pilot study has begun to assess the antibody response to a third dose of an authorised COVID19 mRNA vaccine in kidney transplant recipients who did not respond to two doses of the Moderna or Pfizer-BioNTech COVID-19 vaccine.

THE LIFELONG IMMUNOSUPPRESSIVE THERAPY that organ transplant recipients must take to prevent organ rejection blunts their immune response to both pathogens and vaccines. Research has shown that many organ transplant recipients do not develop antibodies against SARS-CoV-2, the virus that causes COVID-19, after receiving an authorised COVID-19 vaccine regimen.

The purpose of the new study, led by Dorry Segev ( Johns Hopkins University, Baltimore, USA), is to determine whether a third dose of one of the mRNA COVID-19 vaccines could overcome this problem for at least some kidney transplant recipients, which is particularly important because this population has a high prevalence of conditions that are risk factors for severe COVID-19, such as cardiovascular disease and diabetes.

The CPAT (COVID protection after transplant) study also aims to identify characteristics that could help distinguish those kidney transplant recipients who would benefit from a third dose of an mRNA vaccine from those who will require a different approach to achieve protection. The CPAT study’s findings will inform a subsequent, larger phase of the trial that includes higher-risk strategies to induce a protective immune response against SARS-CoV-2 in solid organ transplant recipients who do not respond to a third dose of an mRNA vaccine.

The third-dose vaccine intervention was chosen because of the demonstrated safety of the two-dose mRNA vaccine regimen in solid organ transplant recipients as well as the efficacy of additional doses of other vaccines, such as those for hepatitis and influenza, in immunocompromised people.

The study team will enrol up to 200 adults aged 18 years or older who received a kidney transplant one year or more prior to enrolment, and have had no recent organ rejection or change in immunosuppression. Between 50 and 100 participants will have had no detectable antibody response to two doses of an mRNA COVID-19 vaccine, and 50 to 100 participants will have had a low response. All participants will receive a third dose of the same COVID-19 vaccine that they received previously. Thirty days later, investigators will measure participants’ antibody response to the third dose.

The goal of the study, which is being sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID)—part of the National Institutes of Health (NIH)—is to determine the proportion of participants who achieve a designated antibody response at the 30-day mark. The CPAT study team will follow participants for one year after enrolment, with preliminary results expected later in 2021.

21

Higher kidney transplant referral rates found in non-profit dialysis facilities versus for-profit centres New research indicates that patients with kidney failure who receive care at for-profit dialysis facilities are less likely to be referred for kidney transplants than those receiving care at non-profit facilities. These findings appear in the Clinical Journal of the American Society of Nephrology (CJASN).

treated at for-profit dialysis facilities are less likely than those treated at non-profit facilities to be placed on a transplant waiting list, and to receive a transplant. Little information is available concerning earlier steps in the process, however—namely, referrals and medical evaluations for transplantation.

To investigate, a team led by Patzer and Laura McPherson (Emory University School of Mediur study offers insight into the cine, Atlanta, USA) examined referral and evalpractice patterns related to refer- uation data from all nine transplant centres in ral for transplantation, start of the the Southeastern US states—Georgia, North Carotransplant evaluation at the transplant centre, lina, and South Carolina—as well as information and placement on the national deceased from the United States Renal Data System. donor waiting list—but our study does not have The analysis included 33,651 patients with detailed information about the mechanisms and kidney failure who initiated dialysis in the Southreasons for these differences in referral between east from 2012 to 2016. Some 85% of patients for-profit and non-profit facilireceived dialysis treatments at ties,” said Rachel Patzer (Emory for-profit facilities, and 15% were University School of Medicine, treated at non-profit facilities.

Atlanta, USA), who led the team A total of 44% of patients were conducting this research. referred for transplant during “The reasons for these differthe four-year study period. ences in referral could be due to After adjustments, patients at differences in patients’ health for-profit facilities were 16% Patients at for-profit status that are not measured less likely to receive a referral facilities were 16% in our dataset, or they could than patients at non-profit facilless likely to receive a be due to other unmeasured ities. Rates of starting medical referral than patients factors, such as limited time evaluations within six months of at non-profit facilities to educate or refer patients for referral and placing patients on – out of 33,651 kidney transplant, or unconscious bias. a waiting list within six months failure patients Future research is still needed to of evaluations did not meaninganalysed. better understand these mechfully differ between the groups. anisms, such as through focus An editorial authored by groups, and interviews with patients and care Divya Raghavan and Isaac Hall (University of provider team members.”

Utah School of Medicine, Salt Lake City, USA) Kidney transplantation is the optimal ther- accompanying the report in CJASN notes that apy for most patients with kidney failure. Many “the early steps in transplant access remain fruspatients first initiate dialysis and are referred tratingly opaque, indicating the ongoing need for a transplant by kidney specialists through to address long-standing disparities and ensure dialysis facilities. The researchers note that equity in treatment options for patients with previous studies have reported that patients kidney failure”.

“O

16%

Rachel Patzer

Laura McPherson

Issue 1 – October 2021

22

Latest News

Clinical News Concept Medical provides update on IMPRESSION trial to evaluate MagicTouch AVF

Concept Medical has provided an update on the progress of the IMPRESSION trial—a prospective, multicentre, two-arm parallel group, randomised clinical study designed to assess the efficacy of its MagicTouch AVF sirolimus-coated balloon.

The trial will compare the efficacy of the sirolimus-coated balloon versus a placebo plain balloon—the control arm—in the treatment of dysfunctional, or stenosed, arteriovenous fistulas (AVFs) used for vascular access in haemodialysis.

A total of 170 patients with endstage renal disease (ESRD) are being randomised in a 1:1 fashion between the two groups. The study’s primary objective is to determine if the use of the MagicTouch AVF will result in an improvement in primary circuit patency at six months when compared with plain balloon angioplasty.

The trial is being conducted at three sites in Singapore, led by Chieh Suai Tan (Singapore General Hospital, Singapore). Other site principal investigators include Edward Choke (Sengkang General Hospital, Singapore) and Jackie Ho (University Heart Centre, Singapore).

IMPRESSION team

ESH position paper highlights renal denervation as a third option for hypertension management

The European Society of Hypertension (ESH) presented an updated position paper on renal denervation (RDN) during the eighth pre-ESH congress satellite symposium (10–11 September 2021; Athens, Greece). The paper is also published in the Journal of Hypertension. Written by an ESH expert working group, it confirms that RDN—a minimally invasive procedure to regulate overactivity of nerves that lead to and from the kidney—is considered a safe procedure without significant short-term or long-term adverse effects based on data available up to three years.

In recent sham-controlled randomised trials and registries, clinically favourable effects of RDN have been consistently demonstrated across a wide spectrum of patients with uncontrolled HTN, in the absence and presence of prescribed anti-hypertensive medications.

“Many patients with uncontrolled hypertension struggle to adhere to lifelong drug therapy for a variety of reasons and may look to other options that complement traditional treatments,” said ESH president Reinhold Kreutz October 2021 – Issue 1

Industry News (Charite University Medicine Berlin, Berlin, Germany). “We believe this advance could help clinicians work with patients to better manage their high blood pressure.”

New scoring system measures health-related quality of life in kidney failure patients

Results from a new study support the validity of a score that considers various patient-reported measures and preferences for assessing health-related quality of life, and promoting patientcentred care, in individuals with kidney failure. The study is published in the Clinical Journal of the American Society of Nephrology (CJASN).

The PROMIS (Patient reported outcomes measurement information system) preference summary score—or “PROPr”—is determined from seven domains: cognitive function, depression, fatigue, pain interference, physical functioning, sleep disturbance, and ability to participate in social roles.

When investigators, led by Istvan Mucsi and Jing Zhang (University of Toronto, Toronto, Canada), correlated PROPr with other health measures, their findings supported the validity of PROPr among 524 patients who were undergoing haemodialysis or had recently received kidney transplants.

“Up to 70% of patients with kidney failure experience persistent physical symptoms and emotional distress that substantially impair health-related quality of life,” said Mucsi. “These concerns are under-reported, underrecognised and under-managed. Our results open the doors for the use of PROPr and PROMIS as tools in nephrology research, and in the care of patients with kidney failure.”

Study shows higher risk of renal failure following deep vein thrombosis therapy

A large, single-centre retrospective study has revealed the risk of acute kidney injury (AKI) following pharmacomechanical thrombolysis (PMT) for lower extremity deep vein thrombosis (DVT) is as high as 22%.

As reported in the Journal of Vascular Surgery: Venous and Lymphatic Disorders, a team led by Karim Salem (University of Pittsburgh, Pittsburgh, USA) studied the records of 137 patients who underwent PMT for acute iliofemoral DVT from 2007 to 2018.

Ultimately, 30 of these patients (22%) developed postoperative AKI—two of whom progressed to severe renal failure, with one requiring long-term haemodialysis. Multivariable analysis found three significant risks factors for the development of AKI: Bilateral DVT, single-session PMT and female sex.

“Our focus was to identify the preoperative factors that might influence our decision to pursue aggressive single-stage intervention versus multistage catheter-direct therapy,” Salem said. “With these study results, we avoid single-stage intervention in women with bilateral extensive DVT to minimise the risk of postoperative AKI.”

clearance, but its clinical utility and increased sensitivity have now been seen in six independent datasets— including in the large international, multicentre, prospective Trifecta study, which is expected to be published in early 2022.

Surfacer system

Bluegrass Vascular announces Medicare decision to assign New Technology APC for Surfacer system procedure

Bluegrass Vascular Technologies has announced that the Centers for Medicare & Medicaid Services (CMS) has finalised a new Healthcare Common Procedure Coding System (HCPCS) code and New Technology Ambulatory Payment Classification (APC) assignment for use of its Surfacer Inside-Out access catheter system procedure.

The new code is C9780, Insertion of central venous catheter (CVC) through central venous occlusion via inferior and superior approaches—for example, Inside-Out technique—including imaging guidance. It is assigned to New Technology APC 1534, with a national average payment rate of US$8,250.50.

As a result of this decision, hospitals and ambulatory surgery centres (ASCs) have been able to utilise HCPCS code C9780 to report the Inside-Out procedure when performed with the Surfacer system from 1 October 2021.

The Surfacer system is the first US Food and Drug Administration (FDA)cleared medical device to facilitate upper body central venous access in patients with venous obstructions or other conditions that preclude access by conventional methods, according to a Bluegrass Vascular press release, and is also CE-marked for use in Europe.

Natera launches Prospera with quantification to improve kidney graft rejection testing

Natera has announced the launch of Prospera with quantification, which it claims is the only cell-free DNA (cfDNA) test for kidney rejection that provides three values—the quantity of donorderived cfDNA (dd-cfDNA), fraction of dd-cfDNA, and total cfDNA—on every report. Combining these three metrics has been shown to improve sensitivity when evaluating transplant rejection compared to using dd-cfDNA fraction alone.

A paper published in the Journal of the American Society of Nephrology (JASN) showcased improved performance from Prospera with quantification in 41 kidney transplant patients, nine of whom had rejection.

Incorporating the quantity of dd-cfDNA with the fraction of dd-cfDNA improved the sensitivity of the Prospera test from 78% to 100% across the nine cases of active rejection, which was then confirmed through renal biopsy.

The Prospera test is yet to gain US Food and Drug Administration (FDA)

Alio raises US$20 million in Series B financing

Alio Medical has announced the close of a financing round totalling US$20 million.

The company, which develops wearable technology to enable actionable, remote monitoring of cardiorenal patients, will use the funding to conduct clinical studies on expanded indications and to support its platform’s initial commercialisation.

In addition, Alio will now look to expand its enterprise partnerships within the USA and Europe.

According to a press release, its sensors and remote monitoring platforms offer the ability to decrease the cost and increase the availability of real-time insights on chronic kidney disease and other conditions.

SC+

Quanta announces “largest private funding round in history” for a dialysis device company

Quanta Dialysis Technologies has raised US$245 million in an oversubscribed and upsized Series D financing round—the largest private funding round for a dialysis device company in history, according to a press release from the firm—which will be used to accelerate commercialisation of its SC+ portable haemodialysis system.

The Series D financing round was led

by Glenview Capital and co-led by Novo Holdings, with support from a broad group of other top-tier investors. This funding will allow Quanta to scale up global operations with a focus on the USA, where the SC+ received 510(k) clearance from the US Food and Drug Administration (FDA) in December 2020 for use in acute and chronic care facilities.

The company is investing in “significant infrastructure” to scale up manufacturing, sales and customer service functions to support use in currently approved care settings within the USA, while also preparing to launch a study supporting its future FDA clearance for in-home use of the SC+ in the USA. Quanta’s SC+ system delivers the performance and dose equivalence of larger, traditional dialysis machines alongside on-demand dialysate production, high dialysate flow rates, and the portability, digital connectivity and ease-of-use of a next-generation dialysis device, the release adds.

Section Latest Name News

Industry News Diaverum launches 2021 travel guide for dialysis patients

Diaverum has launched its first ever holiday dialysis travel guide in an effort to “empower renal patients worldwide to live out their dreams of travel, whilst maintaining access to the vital, lifesaving treatments they need”, according to a press release.

The 72-page travel guide combines crucial information on access to the company’s dialysis clinics with travel insights from its renal care experts, patient associations and experienced holiday dialysis travellers. It also provides advice on how to navigate typical travel concerns for dialysis patients, such as nutrition.

Diaverum says its clinic staff help patients at all steps of their holiday planning, from defining an itinerary to ensuring continuity of care at their destination.

The travel guide is available in digital and print format, through its website and clinics worldwide, free of charge.

ImpediMed gains FDA Breakthrough Device designation for digital renal failure platform

ImpediMed has announced that its Sozo digital health platform has been designated as a Breakthrough Device by the US Food and Drug Administration

Events

(FDA) for a proposed indication in renal failure.

Using bioimpedance spectroscopy (BIS), the platform aims to provide clinicians with a more precise measure of fluid volume to be removed from renal failure patients during dialysis.

The current standard-of-care method to measure the accumulation of fluid in kidney failure patients utilises weight scales. These scales cannot account for changes in body composition, however—an ImpediMed press release states—with muscle loss being a common side-effect in end-stage renal disease (ESRD) patients.

“A device that can quickly and easily be used in the dialysis setting to accurately measure fluid volume is currently not FDA-approved and readily available,” said Mark Boiskin (Balboa Nephrology Medical Group, San Diego, USA). “Such a device may significantly improve quality of care and improve patient outcomes.”

Virtual support groups create community for DaVita home dialysis patients

DaVita Kidney Care has launched virtual support groups through DaVita Care Connect, a mobile health platform designed for home dialysis patients, with the aim of creating a community for those undergoing treatment at home.

21–23 October 2021

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

2–7 November 2021

Please be advised that the events listed opposite, because of COVID-19, are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

The support groups, which can be scheduled daily or weekly, encourage live, two-way communication between patients to ask questions and share experiences. These groups are the latest expansion of DaVita’s investments to strengthen its digital home dialysis platforms and help patients in home treatment to experience similar care, confidence and safety as compared to an in-centre experience.

Support specialists and patients cover a wide range of topics in the support sessions, including what to expect when you are new to home dialysis; the path to a kidney transplant; living life to the fullest while on dialysis; balancing family, friends, work and dialysis; and stress management.

Fresenius Medical Care North America announces three key clinical leadership appointments

Fresenius Medical Care North America (FMCNA) has announced three key clinical leadership appointments to help drive priorities, including improving patient outcomes, adopting connected health technologies to support home dialysis and increasing access to transplantation, according to a company press release.

Kathleen Belmonte has been named chief nursing officer and senior vice president of Clinical Services of Fresenius Kidney Care—the dialysis services division of FMCNA. In addition, Benjamin Hippen has been named senior vice president and head of Transplant Medicine as part of the Global Medical Office senior leadership team, the release

18–20 November 2021

Grupo Español Multidisciplinar del Acceso Vascular (GEMAV) Congress Madrid, Spain www.gemav-eventos.com

further details.

Shelly Nash has also been appointed senior vice president and chief medical information officer for FMCNA.

Medtronic gains CE mark approval for Hugo roboticassisted surgery system

Medtronic has announced receipt of a CE mark for its Hugo robotic-assisted surgery (RAS) system, authorising the sale of the system in Europe. This CE mark approval is for urologic and gynaecologic procedures, a company press release states.

The Hugo RAS system was designed to address the historic cost and utilisation barriers that have stifled robotic surgery adoption for two decades, the release adds.

Following this CE mark approval, multiple European hospitals will join Medtronic’s Partners in Possibility programme—a group of pioneering institutions that will be among the first in the world to use the Hugo RAS system and participate in the global patient registry.

Clinicians from these hospitals will engage in hands-on training at Medtronic Surgical Robotics Experience Centers, including two flagship sites operated in partnership with the ORSI Academy in Ghent, Belgium, and IRCAD in Strasbourg, France.

The approval also follows other milestones in the Hugo RAS system global launch, the release concludes, including the first urologic and gynaecologic procedures, which took place in Latin America and India, and marked the start of the Hugo RAS system global patient registry.

24–27 February 2022

World Congress of Nephrology (WCN) Kuala Lumpur, Malaysia and Virtual www.theisn.org/wcn

6–10 April 2022

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

24–25 November 2021

25th European Nephrology Conference London, UK www.europe.nephroconferences.com

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

16–20 November 2021

11–12 December 2021

26–28 April 2022

VEITHsymposium Orlando, USA www.veithsymposium.org/index.php

Controversies in Dialysis Access (CiDA) Summit Dallas, USA www.dialysiscontroversies.org

23

Charing Cross (CX) International Symposium London, UK and Broadcast www.cxsymposium.com/cx2022

Renal Interventions is a trusted, independent source of news and insight from the renal care space.

October 2021 Issue 01 www.renalinterventions.net

In this issue:

Twelve-month Wrapsody results at CIRSE 2021 page 4

AN IMPLANTABLE BIOARTIFICIAL kidney device (iBAK) has moved closer to becoming a reality after being awarded a US$650,000 prize from KidneyX. The device’s creator, the Kidney Project, received this award following the first ever demonstration of its functional prototype.

The Kidney Project is a US-wide collaboration led by Shuvo Roy (University of California San Francisco [UCSF], San Francisco, USA) and William Fissell (Vanderbilt University Medical Center, Nashville, USA).

In the past few years, it has successfully tested the two essential components that make up its artificial kidney technology—a haemofilter, which removes waste products and toxins from blood, and a bioreactor, which replic ates other kidney functions, like the balance of electrolytes in blood—in separate experiments.

To secure KidneyX’s Artificial Kidney Prize, the team married these two units in a scaled-down version of the artificial kidney that is roughly the size of a smartphone and evaluated its performance in a preclinical model following successful implantation. The units worked in tandem, powered by blood pressure alone, to provide continuous renal replacement therapy without the need for blood thinning or immunosuppressant drugs. This technology, which is intended to provide patients with improved mobility and physiological outcomes compared to dialysis, will now be upscaled for more rigorous preclinical testing and, eventually, clinical trials.

For the latest step forward in the development of this device, the Kidney Project team was awarded KidneyX’s Phase 1 Artificial Kidney Prize—becoming one of six winning teams selected from a field of innovators across Canada, Israel, Japan, The Netherlands, Portugal, Singapore, South Korea, the UK, and the USA. Other recipient technologies included a wearable, lightweight, dialysate-free artificial kidney (US Kidney Research Corporation) and genetically engineered pig kidneys designed to increase supplies of transplantable organs (Makana Therapeutics).

Profile:

Alexandros Mallios page 12

Dialysis:

Latest debates dialysis care page 17

in

Transplantation:

Healthcare disparities in the spotlight page 20

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

Bioartificial device receives KidneyX award after reaching preclinical testing

iBAK device

(Credit: UCSF)

Follow Renal Interventions on all our social media platforms for the latest news, insight and events in kidney care

The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) have jointly released a report outlining a new race-free approach to diagnosing kidney disease. In its report, the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recommends the adoption of the new estimated glomerular filtration rate (eGFR) 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation that estimates kidney function without a race variable.

and subsequent treatment of kidney diseases,” said ASN president Susan Quaggin. “By recommending the CKD-EPI creatinine equation refit without the race variable, the task force has taken action and demonstrated how nephrology continues to lead the way in promoting healthcare justice.

It is time for other medical specialties to follow our lead, and NKF and ASN stand ready to help however we can.”

In the USA, more than 37 million adults have kidney diseases and 90% are not aware they have diminished kidney function, the NKF-ASN statement adds, with a disproportionate number of these patients being Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian American, and Native Hawaiian or other Pacific Islander. These patient groups also face “unacceptable” health disparities and inequities in healthcare delivery.

he task force has also recommended the increased use of the protein cystatin C—a commonly used biomarker of kidney function—combined with serum (blood) creatinine as a confirmatory assessment of GFR or kidney function. The final report, which has been published online in the American Journal of Kidney Diseases (AJKD) and the Journal of the American Society of Nephrology (JASN), was drafted with “considerable input” from hundreds of patients and family members, medical students and other trainees, clinicians, scientists, healthcare professionals, and other stakeholders, to “achieve consensus for an unbiased and most reasonably accurate estimation of GFR”, according to a joint statement from the NKF and the ASN. “This recommendation by the NKF-ASN task force is an important step forward in assuring health and healthcare equity,” said NKF president Paul Palevsky. “We commend the task force for the time, thought, thoroughness and effort it took to explore this issue deeply, and recommend the best path forward for us all. The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race. While the work of the task force is an important initial path forward, both of our organisations are committed to continuing to work to eliminate disparities in the diagnosis and treatment of kidney disease.”

“As the largest organisations representing kidney patients and health professionals, NKF and ASN are committed to eliminating health disparities that harm kidney patients, and ensuring that racial bias does not affect the diagnosis

Developing race-free recommendations Over a 10-month period, the NKF-ASN task force organised its work into three phases. The first involved clarifying the problem and evidence regarding eGFR equations in the USA; the second involved evaluating different approaches to address the use of race in GFR estimation; and the third involved providing recommendations based on this.

In April 2021, the task force published its interim report on reassessing the inclusion of race in diagnosing kidney diseases in AJKD and JASN, asserting that race modifiers should not be included in equations used to estimate kidney function, and that current, race-based equations should be replaced by a substitute that is “accurate, representative, unbiased and provides a standardised approach

T

“The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race.”

Paul Palevsky Continued on page 2

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Issue 1 – October 2021

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