March2022 2022 March Issue 02 Issue 02
www.renalinterventions.net www.renalinterventions.net
In this issue:
New directions for access grafts
page 10
page 4
THIS YEAR’S CHARING CROSS symposium (CX 2022; 26–28 April, London, UK, in-person and virtual) will feature a range of key debates in vascular access—primarily pertaining to dialysis patients, but also venturing into other, more novel uses. The CX 2022 Vascular Access Masterclass programme is set to home in on the plethora of innovations that have emerged in vascular access over the past few years, including in the creation of an access—particularly with minimally invasive techniques—but also in maintenance and salvage, with new stents, balloon devices and pharmacological products that have recently become commercially available. Leading physicians from across the globe will present late-breaking data and first-hand experiences, as well as debating and attempting to provide answers to some of the most pressing challenges in the vascular access space. Among the topics scheduled to feature prominently during the second day of the CX symposium (27 April) are vein dilation devices intended to improve arteriovenous fistula outcomes for patients, clinical research assessing drug-eluting balloons in vascular access maintenance, and the various indications that vascular access holds promise for beyond kidney disease. The Vascular Access Masterclass programme will be moderated by CX executive board members Nicholas Inston (Birmingham, UK) and Domenico Valenti (London, UK).
“We really want to tackle all the things that are at the cutting edge of clinical practice in vascular access.”
Profile:
Charmaine Lok page 12
Dialysis:
Houston, we have a problem page 18
Successful xenotransplant procedures provide hope in “unmitigated crisis” of kidney graft shortages
CX Masterclass to examine key challenges in vascular access sphere
Nicholas Inston
CALL TO ACTION: GIRFT report in focus
800,000 Americans defined as having kidney failure
600,000 of them are on dialysis
Fewer than
100,000 are waitlisted
for kidney transplantation. Of those, less than 25,000 are transplanted each year Follow Renal Interventions on all our social media platforms for the latest news, insight and events in kidney care
The global shortage of donor organs has plagued kidney care providers and their patients for years, if not decades, creating long transplant waiting lists and leaving dialysis as the only remaining treatment option—a situation that has become all the more concerning given the recent shift towards transplantation as the much-preferred approach of the two. The past few months have, however, provided a beacon of hope on this front, with a handful of groundbreaking procedures in the USA demonstrating the potential held by xenotransplantation as a means for reducing the need for human donor kidneys.
J
anuary 2022 saw researchers from the University of Alabama at Birmingham (UAB)—led by Jayme Locke (UAB, Birmingham, USA)— publish a study detailing their successful transplantation of genetically modified, clinical-grade pig kidneys into the abdomen of a brain-dead human recipient in the American Journal of Transplantation (AJT). The investigational procedure itself had been performed months prior, in the final days of September 2021, with the subsequent report then undergoing peer review. And, as per a UAB statement, it demonstrated the potential held by xenotransplantation as part of ongoing efforts to overcome global organ supply shortages. “This game-changing moment in the history of medicine represents a paradigm shift and a major milestone in the field of xenotransplantation, which is arguably the best solution to the organ shortage crisis,” said Locke. “We have bridged critical knowledge gaps and obtained the safety and feasibility data necessary to begin a clinical trial in living humans with end-stage kidney disease.” Publication of this study in AJT followed hot on the heels of another similarly momentous development in the field of xenotransplantation. On 25 September 2021, Robert Montgomery (New York University [NYU] Langone Health, New York City, USA) led a surgical team in completing a two-hour procedure whereby a genetically engineered pig kidney was grafted onto blood vessels in the upper leg, outside the abdomen, of a
deceased patient being maintained on a ventilator. “This is a transformative moment in organ transplantation,” said Montgomery. “The medical and scientific communities have been working toward xenotransplantation to sustain human life for more than 50 years. There have been many hurdles along the way, but our most recent procedure significantly moves these endeavours forward. This research provides new hope for an unlimited supply of organs, a potential gamechanger for the field of transplantation, and those now dying for want of an organ.” An “unmitigated” global crisis Speaking to Renal Interventions, Locke outlined the dire predicament facing the global kidney care community, and US kidney disease patients in particular. About 37 million Americans currently have chronic kidney disease, she details, and, while more than 800,000 of these are defined as living with kidney failure, the majority never even make it to the transplant waiting list due to severe shortages of human donor organs. Furthermore, while the need for them has soared, the number of usable, donated organs available for transplantation has not grown sufficiently over the past half century. According to data compiled by the Organ Procurement and Transplantation Network of the US Department of Health and Human Services, there were more than 90,000 people awaiting a life-saving kidney transplant in the USA as of late-2021. “Fewer than 100,000 people are wait-listed for kidney transplantation and, of those, less than 25,000 are transplanted each year,” Locke said. “The bottom line is that [this] is an unmitigated crisis. Finding an alternative source of organs is needed, and xenotransplantation offers the opportunity to have a cure available to everyone in need.” And, when asked what the future may look like for kidney disease patients if this current upward trend in xenotransplantation continues, Locke added: “Quite literally, we could actually have a supply of donor kidneys that meet this demand.” Xenotransplantation breaks new ground As director of the Comprehensive Transplant Institute in UAB’s Department of Surgery, Locke played a pivotal role in the most recent breakthrough in xenotransplantation. In their AJT study, Continued on page 2
Xenotransplantation
Successful xenotransplant procedures provide hope in “unmitigated crisis” of kidney graft shortages Continued from page 1
she and the UAB researchers set out to test a preclinical model for transplanting genetically modified porcine kidneys into a human recipient following the removal of their native kidneys. The transplanted kidneys filtered blood, produced urine, and were not immediately rejected, and they also remained viable until the study was ended 77 hours after transplantation. The transplanted kidneys were taken from pigs that had been genetically modified with 10 key gene edits designed to reduce the likelihood of immune rejection and make them suitable for transplantation into humans. As per a UAB statement, this process “demonstrates the long-term viability of the procedure and how such a transplant might work in the real world”. Such genetically modified pig kidneys have been extensively tested in non-human primates to date—and evaluations in human preclinical model research may now be key in providing important information about their potential safety and efficacy in human transplant recipients, including in clinical trials. “This human preclinical model is a way to evaluate the safety and feasibility of the pig-to-nonhuman primate model, without risk to a living human,” Locke added. “Our study demonstrates that major barriers to human xenotransplantation have been surmounted, identifies where new knowledge is needed to optimise xenotransplantation outcomes in humans, and lays the foundation for the establishment of a novel preclinical human model for further study.” Locke also noted that the study “validated several key elements that needed to be answered without risking a living human life”, including: Using a flow crossmatch test, allowing a priori predictions of tissue compatibility between donor and recipient prior to the transplant Finding that a clinical-grade porcine donor from a pathogen-free facility did not transmit porcine endogenous retroviruses Observing that the porcine kidney vasculature tolerated human arterial pressure Replicating every step of a standard kidney transplant, with the only difference being a porcine donor source instead of human, and approximating potential steps for a future phase 1 xenotransplantation clinical trial. Many of the broader components of this trial had also been seen in the procedure announced by NYU Langone Health back in September. Montgomery and colleagues ‘knocked out’ the gene that encodes the glycan, known as alpha-gal, which is responsible for a rapid antibody-mediated rejection of porcine organs by humans, in the donor pig. They also transplanted the pig’s thymus gland alongside the kidney to stave off novel immune responses.
The transplanted kidney was then covered with a protective shield for observation and tissue sampling over the 54-hour period of study. Key kidney function indicators like urine production and creatinine levels were normal, and “equivalent to what is seen from a human kidney transplant”, as per NYU Langone Health’s announcement at the time. Throughout the operation and the observation period, no signs of rejection were detected, and the results of this study are now set to be presented for peer review and subsequent publication. On 13 December 2021, NYU Langone Health announced a second successful investigational xenotransplantation procedure as part of the same ongoing study. This operation was very similar to the first in terms of process, recipient, and outcomes, and was once again led by Montgomery. “We have been able to replicate the results from the first transformative procedure to demonstrate the continued promise that these genetically engineered organs could be a renewable source of organs to the many people around the world awaiting a life-saving gift,” he said. “There is much more work to do before we begin living human trials, but our preliminary findings give us hope.” Another thing that was consistent—not only
Jayme Locke
Robert Montgomery
“The potential here is incredible. If the science and experimentation continue to move ahead positively, we could be close to kidney xenotransplantation into a living human being.” Robert Montgomery
Xenotransplant team at UAB
between these two New York-based surgeries, but also with the xenotransplantation breakthrough achieved almost 1,000 miles further south in Alabama earlier this year—was the technology that made them possible. This came courtesy of Revivicor, a regenerative medicine firm and subsidiary of United Therapeutics headquartered in Blacksburg, Virginia. The company’s UThymoKidney innovation was transplanted by Montgomery and his team, indicating that its gene-edited GalSafe pigs— approved by the US Food and Drug Administration (FDA) for certain biomedical research uses in 2020—can “transcend the most proximate immunological barriers to xenotransplantation”. An alternate Revivicor product, its gene-edited investigational xenograft, UKidney, was deployed in Locke and colleagues’ procedure. The UKidney was taken from ‘10-gene’ genetically modified pigs—the same animals that were the source of another recent and equally historic xenotransplantation surgery. On 7 January 2022, Bartley Griffith (University of Maryland School of Medicine [UMSOM], Baltimore, USA) led a team in successfully transplanting a genetically modified pig heart into a terminally ill patient, utilising Revivicor’s UHeart xenograft. UMSOM follow-up reports later in the month noted the patient had reached a two-week milestone, and was demonstrating continued postoperative cardiovascular improvement with normal organ function. What does the future hold? Discussing the most recent of these additions to the xenotransplantation research landscape in AJT, Locke and colleagues write: “We addressed critical safety and feasibility questions in xenotransplantation by using a novel, preclinical human model under significant regulatory oversight. Our results add significantly to the prior knowledge generated in non-human primate models and suggest that many barriers to xenotransplantation in humans have indeed been surmounted. Importantly, the decedent model identified numerous areas where additional understanding is needed, and all of our results must be interpreted cautiously within the numerous limitations of the model. “Whether the new knowledge and process gaps identified by our study can be addressed using the decedent model, or a combination of in vitro studies with preclinical animal models and even clinical trial data in living humans, remains to be determined. Nevertheless, the decedent model has significant potential to propel not only the field of xenotransplantation forward but to answer a multitude of other scientific questions unique to the human condition.” Locke reiterated that this procedure has paved the way for further research of xenotransplantation—not least because the study was conducted to meet standards directly comparable to those that would apply to an in-human study. “We are now actively working with federal regulators (FDA) and our institutional review board toward a phase I clinical trial in living persons in the coming months to years,” she told Renal Interventions. “We continue to make progress with the single-gene knockout xenotransplantation,” Montgomery added following the second procedure at NYU Langone Health. “The potential here is incredible. If the science and experimentation continue to move ahead positively, we could be close to kidney xenotransplantation into a living human being. This is an extraordinary moment that should be celebrated—not as the end of the road, but the beginning. There is more work to do to make xenotransplantation an everyday reality.”
Editor-in-chief: Nicholas Inston | Editorial Board: Ziv Haskal, Stephen Hohmann, Robert Jones Publisher: Roger Greenhalgh | Content Director: Urmila Kerslake | Editor: Jamie Bell jamie@bibamedical.com | Design: Terry Hawes, Wes Mitchell Advertising (EU): Shilpa Suthar shilpa@bibamedical.com | Advertising (US): Nicole Schmitz nicole@bibamedical.com Subscriptions: subscriptions@bibamedical.com | News or advertising queries: Tel: +44 (0)20 7736 8788 Published by: BIBA Publishing, which is a subsidiary of BIBA Medical Ltd BIBA Medical, Europe, 526 Fulham Road, Fulham, London, SW6 5NR, United Kingdom Tel: +44 (0) 20 7736 8788 | BIBA Medical, North America, 155 North Wacker Drive, Suite 4250, Chicago, IL 60606, United States Tel: +1 708-770-7323 Printed by: Buxton Press Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the United Kingdom address. © BIBA Medical Ltd, 2022. All rights reserved. If you have comments on this issue or suggestions for upcoming editions, write to jamie@bibamedical.com
Renal Interventions March 2022 – Issue 2
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October 2021 Issue 01 www.renalinterventions.net
In this issue:
Twelve-month Wrapsody results at CIRSE 2021 page 4
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:
Alexandros Mallios
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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4
Arteriovenous Grafts
Special Feature on AVG Not always ‘the alternative’: Are arteriovenous grafts unfairly maligned? The arteriovenous graft (AVG) for use as a dialysis conduit is a story of innovation, disappointment, intrigue, politics and hope. A recent recalibration of guidelines from “fistula first” to the “right access” may see these easy-to-use, off-the-shelf devices move from a second-line option to take their rightful place within the treatment algorithm for end-stage kidney disease (ESKD) patients. However, these hopes rest on reversing their reputation for being infection-prone, requiring frequent interventions and lacking durability following repeated cannulation, argues Nicholas Inston (Queen Elizabeth Hospital, Birmingham, UK). SYNTHETIC CONDUITS WERE tion has been enhancing the structure of pivotal in turning renal failure from a the ePTFE layers within a graft, allowing fatal into a chronic condition. The Scrib- early cannulation, with many grafts being ner and Buselmeier shunts gave hope of used today with the intent of postoperative survival but were plagued by failure and cannulation mere hours or days—rather complications. Then, the Brescia-Cimino than weeks—after access creation. fistula, described in 1966 using the wrist There are few quality prospective studies vessels, allowed for repeated cannula- directly comparing these newer grafts with tion with low infection and demonstrated traditional ePTFE, or other comparators improved good longevity (Editor’s note: including central venous catheters (CVCs) Michael Brescia and James Cimino were and fistulas. Longer-term data on graft both nephrologists and the fistulas were damage and degradation again are scanty. created by the surgeon, Kenneth Appel). The way that grafts are used may be just Despite this, many patients were unsuita- as important as the type of graft material. ble for graft implantation, and innovations If grafts are used as a second-line option in the development of grafts included after fistula failure, it is likely that results, biological as well as synthetic conduits. particularly regarding patient survival, The introduction of expanded polytet- will be unfavourably skewed. Lead time rafluoroethylene (ePTFE) as a graft effect also needs to be considered, as does material marked a major step forward in risk stratification to allow comparisons. off-the-shelf options for vascular surgery, Using grafts to avoid CVC deployment, and this extended into dialyeither as a first access or to sis access use. AVGs became salvage autologous access, the predominant vascular may influence outcomes as access mode in the USA— well as the type of graft propbut their use as a first-line erties required. option was widely chalIn patients with more lenged. Despite good early challenging anatomies for patency, studies repeatedly cannulation, a graft may showed the rates of interbe a desirable approach vention were higher with Nicholas Inston compared to using deepgrafts than with native arteer-lying veins for a fistula— riovenous fistulas (AVFs). Infection rates particularly when staged procedures and management of infection were more could require a bridging catheter. We need challenging with synthetic conduits and to rethink long-held assumptions regardoverall patient survival was shown to be ing vascular access grafts. Data need to be worse than in those with a native fistula. carefully scrutinised and risk adjusted. The Initiatives such as Fistula First and comparators may not be fistulas, but CVCs. other incentives have promoted the The choice of graft and the timing of benefits of a fistula and, whilst this is not placement need to be considered, as do contested, the reputation of grafts has the patient’s presentation, life plan and suffered. Now designated a second-line dialysis needs, so that AVGs are considaccess in the guidelines, AVGs have devel- ered in a more holistic, patient-driven oped a maligned reputation, but do they algorithm, rather than considered as a deserve this? second-line approach after exhausting The main research base that these fistula options. data were generated from used standard Dialysis access is no longer suited to a ePTFE grafts. This material, while having ‘fistula-is-first-and-only-option’ approach, excellent properties, was never designed and grafts may have been maligned but for use in dialysis patients. Repeated their place in vascular access should not cannulation results in graft wall degen- be understated. That is one of the key eration and prothrombotic tendency. In reasons why this issue of Renal Intervenaddition, material mismatch promotes tions hosts a specific feature aimed at stenosis at the venous outflow and examining these questions and approachfrequent needling brings with it the risk ing solutions. of introducing infection. As a consequence, the results associated with graft use appear poor. However, continued innovation in graft design over the last two decades has led to the development of both biological and synthetic AVGs, specifically for dialysis use. Materials like polyurethane have shown promise, but the main clinically translatable innova-
“We need to rethink long-held assumptions regarding vascular access grafts.”
March 2022 – Issue 2
A raft of new directions for vascular access grafts A departure from the “extreme mantra” of Fistula First unlocks the door to a new, dynamic vision that could swing the pendulum back to increased arteriovenous graft (AVG) use. But, this hinges on shared decision-making with patients and sight lines being firmly set on “long-term strategy for a patient’s entire dialysis journey”. It will also involve conversations around options that include arteriovenous fistula (AVF), early-cannulation AVG (ecAVG) and tunnelled central venous catheter (TCVC). Then, availability, applicability— including timing and anatomy—and how each device handles and performs, will determine the choice of which one to use, say experts, who also highlight the plethora of innovations vascular access grafts have undergone.
M
atteo Tozzi (University of Insubria, Varese, Italy) captures an entire field of thinking when he says AVGs are often seen as a “necessary evil”—their implantation and value accepted as collateral for avoiding TCVC placement (the latter devices are generally perceived as the real offender and last resort of access options and maintenance as their use is entwined with increased central venous stenosis, infection and higher all-cause mortality). Tozzi believes that the most recent Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines from 2019 breathe fresh life into expanding the scope of AVG placement. But, he contends, this relies on distinguishing patients into two categories—those predicted to have adequate native fistula maturation for dialysis and those in whom this is unlikely. In the second group, early-cannulation prosthetic grafts offer the possibility of rapid haemodialysis initiation followed by a switch to a native fistula, he opines. Those who have a long history of several failed access procedures, and older, frail patients, are also suitable candidates for graft placement.
Considered AVG implantation gains groundswell of support Tozzi’s view is that, while Fistula First was a fantastic initiative, it also inadvertently resulted in many patients relying on long-term CVC for dialysis when their “first” native access did not mature, and was therefore unutilised. The latest KDOQI revision focuses on attainment of the “right access, in the right patient, at the right time, for the right reasons”, which resolves that policy wobble, he says. The change also signalled a shift from choosing between an AVF and AVG to a more dynamic vision in which, depending on the patient, an ecAVG could be a solid first path to dialysis, after which an AVF is created and matured to enable a subsequent switch. The core of this argument rests on research from David Kingsmore (University of Glasgow, Glasgow, UK), who insists that “the preconceptions surrounding graft use are not based on evidence” and that they are “inappropriately discredited”. He explains how grafts can be used in novel ways, not to compete with AVFs, but to reduce the use of CVCs. “The biggest misperception is the comparative outcomes of AVGs versus the alternatives that clearly demonstrate AVGs are a worthwhile consideration in patients without an obvious good target for an AVF that leads to potentially unnecessary TCVC use,” Kingsmore adds. He is convinced that current clinical practice should consider AVG use best suited to “anywhere an AVF will not be available for dialysis— whether it is dysfunction of an existing AVF, failed AVF procedures, or urgent starts”. Kingsmore continues: “Most importantly, their use benefits younger, female patients with diabetes in whom the short- and longer-term consequences of TCVC tend to be: infection, repeated procedures, central vein stenosis and the knowledge that, even if transplanted, 50% will require additional dialysis in 10-to-15 years.” Interjecting on graft advances he would welcome, he adds: “The main innovation we need is for new technology to guide the need for intervention for venous stenosis. We currently have good grafts and good treatments for the main complication, venous stenosis, but there
Arteriovenous Grafts
are interesting developments in remote, self-reporting, intelligent stents that would negate the need for surveillance”. Shared decision-making involving patients is key Some physicians believe that procedure-driven incentivising is the real malignant force. Karen Stevenson (University of Glasgow, Glasgow, UK) emphasises that the rightful place for any device, including “maligned” grafts, is best brought to light when their use is aligned to the needs of the patient. So, determining where grafts might be a good fit for patients—rather than being driven by a fixed access type—is the guiding principle. Tozzi concurs that access creation is a bespoke and tailored procedure. “Today, this procedure is very heterogeneous. The patient population is extremely diverse and there is often only one type of right or correct access. Creation needs to be tailored to the patient, and the patient and proceduralist need to go together to achieve the goal of vascular access,” he says. “Dialysis access decision-making has changed significantly with the development of ecAVGs,” Stevenson states. “They offer options to patients at decision points in their care that can alter their vascular access journey, such as with urgent haemodialysis start or to manage an AVF complication where previously the only option on offer was TCVC. The challenge is how to implement in practice if providers are working in silos.” Patients’ views on grafts form a fundamental basis on which graft use might be accelerated, if appropriate, notes Stevenson. “In deriving the Vascular Access Quality of Life measure (VASQoL; a validated 11-item vascular access-specific quality of life measure), patients described hugely variable vascular access journeys,” she says. “Consistent themes were that, whilst their vascular access function, appearance and feel were very important, key findings were that creating and maintaining an access that did not interfere with activities they really needed to still be able to do (work/caring) and that they wanted to take part in (hobbies/interests) had a great impact on kidney failure patients’ quality of life. Specifically, patients wanted to be included in decisions about the care of their access—which confirmed the importance of shared decision-making.” Stevenson sets out her vision clearly, adding: “In the past, dialysis access research has been procedure- or intervention-based. I hope, in 2022, that we can shift our focus and research to an approach that is more patient-centred, and involves shared decision-making and long-term strategy for a patient’s entire dialysis access journey. We need to shift away from consultations that are single procedure-based and involve patients in the decisions about creation and longterm maintenance of their vascular access. That requires conversations that include fistula, TCVC and ecAVG options.” Overcoming the pitfalls of arteriovenous grafts Still, before widespread AVG use is accepted, the chinks in their reputation for longevity and infection rates need to be faced down. Right on cue, InnAVasc’s founder and director of Clinical Operations Shawn Gage reminds readers that it is always “important to recall that the standard AVGs still used for the majority of arteriovenous access were never specifically engineered to be stuck with a dialysis needle”. He also notes: “They were developed to be peripheral arterial replacements, so it is surprising that we have gotten away with using them for haemodialysis for as long as we have. They were disadvantaged from the beginning. “Grafts certainly serve a very important
Left: Axess Below: IG
purpose in the access lifecycle for most patients with end-stage kidney disease [ESKD]. I think there are now decades of experience to showcase how grafts perform in comparison to AVFs and catheters. In general, this is defined as somewhere in the middle in terms of patency, longevity and infection. In some patients, grafts are the only mode of vascular access that can function reliably. But, we can do better for our patients.” Responding to the question: “Does the evidence back the claims that these devices are more prone to infection and thrombosis?”, Gage says: “If one excludes fistulas that fail to mature, I think it is reasonable, in general, to accept (based on decades of data) that autologous AVFs tend to have a lower incidence of infection and thrombosis than AVGs. This is mostly a biological issue. AVGs do not favourably incorporate into the surrounding tissue, but rather scar. This does not lend itself toward enjoying the rich microvascular environment that is native to autologous access. “Therefore, AVGs are less efficient at eradicating unwanted bacteria that may have been introduced via dialysis needle or from within the blood stream. Furthermore, AVGs do not develop an endothelium and can often exhibit more extreme flow dynamics at the venous juxta-anastomotic zone, which heavily influences neointimal hyperplasia of the venous outflow, both of which contribute to the increased thrombogenicity of AVGs.” In addition to grafts dedicated for haemodialysis, including the development of ecAVGs, there are several new lines of innovation that have transformed both the standard prosthetic AVG and biological grafts. Chief among them, Tozzi notes, are new biological and biosynthetic grafts, such as the Axess graft (Xeltis)—an endogenous tissue regeneration graft—or a graft crafted from silk cocoons in which the fibrin has very good biological properties. Novel devices offer promise in vascular access Xeltis recently announced initiation of a clinical trial evaluating its Axess graft, which it claims is the first ever restorative synthetic graft. “Axess grafts enable early puncturing shortly after implanting. Over time, they turn into living blood vessels as their porous microstructure is colonised by the patient’s own tissue,” according to a company press release shortly following the announcement. Several patients requiring dialysis have already been successfully implanted as part of the European first-in-human trial. Elaborating on this futuristic implant—a graft built from biosynthetic polymer—which after some months is completely regenerated with live tissue from patients, Tozzi notes that in time this graft transforms into a tube lined by the patient’s own cells, owing to the fact it is based on endogenous tissue restoration technology. Innovative steps are being taken on the
The panel
Matteo Tozzi
David Kingsmore
Karen Stevenson
Shawn Gage
5
other side of the Atlantic too—with US-based clinical-stage biotechnology firm Humacyte developing their own solution to some of the most pressing challenges faced by AVGs. More specifically, it is attempting to tackle a prevailing problem associated with graft materials like polytetrafluoroethylene (PTFE) by proposing a biological alternative. The company is currently working on a universally implantable bioengineered human tissue—a human acellular vessel (HAV)—at commercial scale. These HAVs are created by culturing human vascular smooth muscle cells on a biodegradable polymer matrix within bioreactors that provide pulsatile mechanical strain. The final, completed vessel comprises human vascular extracellular matrix constituents and has the mechanical strength of the original vessel, without cellular components that might stimulate immunologic recognition in the host. Late last year, five-year data from a phase 2 clinical trial of 29 patients who received Humacyte’s HAV for arteriovenous access in haemodialysis were presented at the American Society of Nephrology (ASN) Kidney Week (2–7 November 2021, virtual). These data suggested long-term durability and functional haemodialysis access in patients with ESKD who dialyse three times per week, with the study’s authors also reporting no HAV conduit infections during follow-up. Freedom from needless needlestick injuries The InnAVasc Graft (IG) is designed to reduce the risk of complications and bleeding from repeated dialysis for both in-centre and home haemodialysis, allow for immediate use post-implant, and promote easy location of a safe stick zone target. The company states that the IG has been designed specifically to address three key issues: back and side wall injury (via protective backplates), excessive bleeding (using self-sealing materials specifically engineered for needle sticks) and lack of cannulation confidence (with easy-to-identify raised target stick zones). In January this year, InnAVasc announced receipt of US Food and Drug Administration (FDA) permission to commence the third phase of enrolment for a pivotal clinical study assessing safety and effectiveness with IG, which is designed to be used immediately post-implant. Declaring his interest, Gage—who has been working on this device with the view to protecting patients from all-too-frequent cannulation-related injuries—says: “I think there are huge potential advances on the AVG front with the IG and also from an overall renal care perspective.” Gage predicts a “swinging of the pendulum” back towards grafts over the next decade. “From significant AVF and AVG data, we realise that not all AVFs are good and that AVGs have a solid value in the arteriovenous access lifecycle,” he continues. “It is no secret that, when fistulas work, they can work really well, but both modes of vascular access play a critical role for our patients. We are in the process of transitioning from the extreme mantra of Fistula First to a more reasonable practice of ‘the right access, for the right patient, at the right time, and for the right reasons’. If we continue to review all relevant factors with our patients as outlined in the ESKD Life-Plan [a concept introduced by the National Kidney Foundation as part of its 2019 KDOQI guideline update] as we go forward, that will likely include better planning for AVFs, decreased use of catheters, and increased use of AVGs.” Many of these graft innovations are set to feature at the Charing Cross symposium (CX 2022; 26–28 April, London, UK, in-person and virtual).
Issue 2 – March 2022
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Device-created Fistulas
Benefits of percutaneous fistula creation further bolstered by five-year Ellipsys data The Ellipsys vascular access system (Medtronic) can be used to easily and safely create durable percutaneous arteriovenous fistulas (pAVFs) for haemodialysis—with new, long-term data suggesting it offers an “excellent alternative” to AVF creation via surgical procedures in end-stage kidney disease (ESKD) patients. That is according to Jeffrey Hull (Richmond Vascular Institute, Richmond, USA) who presented fiveyear results from the Ellipsys US pivotal trial at the American Society of Nephrology (ASN) Kidney Week (2–7 November 2021, virtual).
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nd, speaking to Renal Interventions shortly after this event regarding the role device-created AVFs now play within access creation strategies, Hull stated: “Once you get past the wrist issue, I would say it could be percutaneous fistula first. If you have suitable anatomy for a fistula, but are not a great wrist fistula candidate, then maybe the first possible fistula that should be considered for you is a percutaneous fistula—and I think the data are promising enough to support this.” Hull opened his ASN Kidney Week presentation with an overview of the Ellipsys US pivotal trial, a prospective, multicentre, single-arm study intended to evaluate the safety and effectiveness of AVF creation using Ellipsys. It involved a total of 107 patients treated across five outpatient, office-based labs, he reported, adding that—aside from the fact 76 (71%) were male—the baseline characteristics of these patients were “typical of those seen in dialysis patient populations”, in terms of mean age (56.6 years) and obesity prevalence (50%).
Moving on to summarise one-year data from this trial, Hull reported technical and clinical success rates were both 95%, with an average procedure time of 24 minutes being observed. One-year fistula-related Jeffrey Hull events including thrombosis, stenosis, cannulation-related injuries or difficulties, and steal syndrome, generally looked “very similar” to those seen in surgically created fistulas—something that he stated was “a little disappointing” at that stage. He did add, however, that the trial’s primary efficacy endpoint was met, with 86% of the 107 patients’ fistulas being mature at 90 days, as was its primary safety endpoint, due to there being no serious, device-related adverse events. Discussing the crux of his ASN Kidney Week presentation, Hull reported that a total of 85 patients were eligible for further follow-up at one year and continued to be followed out to five years. Regarding the first of several long-term endpoints—fistula use, assessed by two-needle cannulation—Hull told the audience that 92% of these fistulas were used in patients requiring dialysis, describing this as “an excellent outcome” that compares favourably to the 63% rate of two-needle cannulation observed in US patients with surgically created fistulas. He further noted that fistula non-use was low, with 11 of the 24 patients whose percutaneous fistula was unused ultimately not requiring haemodialysis. Outlining access complications through five years, Hull said 27 patients experienced complications including fistula dysfunction (21.2%), cannulation injury (12.9%), thrombosis (5.9%) and arm swelling (4.7%), with these being typical of those seen in dialysis patient populations.
Largest patient series to date reinforces 4Fr WavelinQ system’s potential in dialysis access A MULTICENTRE EXPERIENCE WITH THE 4 French (4Fr) WavelinQ endoAVF system (BD) has found that the device is safe and effective, bolstering existing evidence that it could offer an alternative option to surgically created arteriovenous fistulas (AVFs) in the dialysis access algorithm. The study, and this viewpoint, were presented by Bulent Arslan (Rush University Medical Center, Chicago, USA) at this year’s International Symposium on Endovascular Therapy (ISET 2022; 16–19 January, Hollywood, USA). The speaker began by noting that he was not directly involved in the presented study—which has been published by Todd Berland (New York University, New York, USA) and colleagues, in the Journal of Vascular Surgery (JVS). Arslan outlined key differences between the second generation 4Fr WavelinQ system and the older 6Fr system, detailing that the former enables radial-to-radial AVF creation, in addition to the ulnar-to-ulnar option, and also has a smaller profile. Discussing the JVS study, he stated that it aggregated findings from three different, prospective studies (EASE, EASE-2 and EU/CA) conducted across Canada, Europe and South America. The sum patient population was 120 (97 males [80.8%], mean age=54.6), with the objective being to analyse safety and performance data in patients treated with the 4Fr WavelinQ system.
Procedural success was achieved in 116 patients (96.7%) and the investigators reported a mean procedure time—from initial puncture to applying dressing—of 84 minutes. Regarding location, a little over three quarters of the fistulas were ulnar-ulnar anastomoses. “But, with the 4Fr device, more and more radial procedures are being performed,” Arslan noted. He said the study also found a primary patency rate of 85% at three months across the aggregated studies, and 72% at six months. Relaying data on secondary patency—which he stated are “more important”—Arslan reported a rate of 94% at three months and 88% at six months. He then moved on to another “important criteria”, haemodynamic maturation (defined as 500ml/ Bulent Arslan
Primary patency rates
85%
at three months
72% at six months
Secondary patency rates
94% at three months
88% at six months
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A total of 91 additional procedures were performed to rectify these issues, he stated, with the majority of these being balloon dilatations (78%). Hull also noted, regarding additional procedures per patient per year in the trial, that this figure (2.66) was similar to those associated with surgically created fistulas at one year but that, in years two through five, a “drastic reduction” in additional procedures per patient per year— ranging from 0.18 to 0.57—was observed. “We attribute that to the low-to-moderate flow in these [percutaneous] fistulas...and also their multi outflow feature whereby, if an injury occurs, the blood will flow around it and keep the fistula operational until it can be repaired,” he said. Referencing the final long-term endpoint from the trial, Hull relayed “excellent” primary assisted and secondary patency rates of 74% and 82%, respectively, at five years, as per Kaplan-Meier estimates, while the functional patency rate was found to be 91.8%. “In summary, this follow-up study has shown us several important things—the first being that high-quality fistulas can be created by interventional nephrologists,” he concluded. “Secondly, we have expanded the places in which these fistulas can be created, not just in the hospital but now in office-based labs and ambulatory surgery centres too.” In addition to reiterating the five-year high fistula usage, positive long-term patency outcomes, and low complication rates and subsequent maintenance procedures seen in the study, Hull noted that the goal now is to reduce time to two-needle cannulation with Ellipsys, and cannulationand cost-related issues are also set to be evaluated further.
“If you have suitable anatomy for a fistula, but are not a great wrist fistula candidate, then maybe the first possible fistula that should be considered for you is a percutaneous fistula—and I think the data are promising enough to support this.” Jeffrey Hull
min and access vessel diameter >4mm), noting rates of 10.5%, 80.2% and 87.4% at 30 days, three months, and six months, respectively. Regarding functional patency, the speaker reported rates of 96.7% at three months and 94.1% at six months following two-needle cannulation—meaning roughly 6% of fistulas were abandoned as dialysis access options at six months. Successful cannulation (defined as two-needle cannulation and dialysis through the fistula) was achieved in 63.5% of patients at three months and 78% at six months, and the median time to successful cannulation was found to be 49 days. Arslan noted “relatively low” access circuit reintervention rates with survival probabilities of 93.3% and 80.7% at three and six months, respectively. There was also a total of 23 (19.2%) maturation- or maintenance-related reinterventions across the 120 patients and 0.55 reinterventions per patient year (PPY). On safety outcomes, Arslan said there were three device-related serious adverse events (2.5%) and seven procedure-related serious adverse events (5.8%), while arterial/venous access complications were not reported in any patients. According to Arslan, these results are largely similar to those seen in other published studies and experiences with the 4Fr WavelinQ device from across the globe, including the pivotal NEAT trial. “In summary, this study comprises 120 patients and is therefore the largest WavelinQ endoAVF series to date,” he concluded. “There are encouraging comparisons to surgery, and the 4Fr WavelinQ may provide an additional option in the access algorithm for dialysis patients.” Issue 2 – March 2022
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Vascular Access Cannulation
Systematic review sheds light on “unpleasant necessity” of cannulation for haemodialysis patients A systematic review published in the Journal of Vascular Access ( JVA) has illuminated haemodialysis patients’ views and experiences of arteriovenous access cannulation, concluding that many patients learn to tolerate its unpleasantness out of a sense of necessity, with feelings of safety and control over the procedure often helping to facilitate this.
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atients learn to survive repetitive They also report that patients viewed difficult cannulation, where feeling safe cannulation as having a direct and negative and in control can improve their impact on haemodialysis treatments’ effectiveexperiences,” Catherine Fielding (University ness, and worried about damage to their arteriHospitals of Derby and Burton NHS Founda- ovenous access following difficult cannulation. tion Trust, Derby, UK) and colleagues write in The third and final theme identified by the their JVA report. “This indicates cannulation is authors is the role necessity and regularity of not just a technical skill, but also a social process. cannulation for haemodialysis play in helping Cannulators and haemodialysis environments patients to overcome, or at least endure, these need to make patients feel safe and in control. procedures. They report that patients often learn “Cannulation techniques may also influence to tolerate, or become used to, cannulation. Feelthese aspects, but further research is needed to ing safe—a factor influenced by the environment determine how. Whilst this review has helped in which it is conducted, the cannulation techfurther develop our understanding about nique used, and even the patient’s relationship patients’ experiences of cannulation for haemo- with and level of trust towards their cannuladialysis, there is still much to understand about tor—was found to influence patients’ ability to this phenomenon, to continue to improve this tolerate the procedure, as was their capacity to for haemodialysis patients.” exert some control over the cannulation. On this Fielding and colleagues begin by noting that front, self-cannulation was found to provide a cannulation is an essential part of haemodialy- sense of achievement, creating independence sis—yet patients’ experiences are problematic and self-sufficiency, despite being associated and poorly understood. As such, they set out with its own challenges. to assess the existing literature in this space, “Finally, not all patients were able to cope with conducting a qualitative systemthe unpleasantness of cannulation, atic review to synthesise studies leading to some avoiding cannulathat explore patient experiences tion,” Fielding and colleagues add. of cannulation, vascular access “Some did this by reducing the (VA) and haemodialysis. frequency of haemodialysis […] The authors conducted a dataothers felt ‘it would be easier to do base search in May 2019 to identify it having line access because of the eligible studies pertaining to popuway the hook-ups work’. However, lations of patients with end-stage where possible, some patients kidney disease (ESKD) within the Catherine Fielding completely avoid haemodialysis context of both in-centre and due to thoughts of the cannulation.” home haemodialysis. Following the removal of Discussing their findings, the authors note duplicates and two stages of screening, a total that the necessity of cannulation and its link to of 26 studies from across five continents were life-sustaining haemodialysis contributes to a included in the final analysis. “Only four stud- “heavy burden” for patients, and concern over ies were directly about cannulation,” Fielding miscannulation is central here. “Whilst preventand colleagues report. “Other studies were about ing miscannulation is the optimal solution, it is pain, experiences of VA for haemodialysis, expe- unlikely that it can be avoided completely,” they riences of in-centre and home haemodialysis, add. “Therefore, better strategies are also needed and research priority setting.” to support patients through miscannulation.” Regarding the content and findings of these Regarding potential improvements to this studies, the authors identified three key themes state of affairs, they claim that cannulators, but and 10 sub-themes on patients’ experiences also managers who influence nursing schedules of cannulation. “Cannulation creates unpleas- and workloads, should “aspire to create a calm ant feelings and is not a normal procedure for haemodialysis unit that makes patients feel safe patients to experience regularly,” they write, to undergo cannulation and survive its unpleasdiscussing the first of three overarching themes. antness”. They further note that cannulation “Cannulation for haemodialysis is associated technique appears to influence whether patients with pain, concern about the abnormal appear- feel safe in these settings—but that, in their ance of the arteriovenous access, vulnerability meta-analysis, explorations into such a phenomand dependency. The context of regular haemo- enon were limited, and additional research is dialysis makes this a unique procedure that is now needed to elucidate this link. not similar to other one-off cannulation events.” In addition to the unpleasant and unique nature of cannulation for these patients, the second major theme identified by the authors is the fact it is something of a necessary evil in haemodialysis—and patients themselves are accepting of this. This link to a life-sustaining and essential treatment changes what cannulation success means, they add, and leads to additional worry over whether it will be successful. Drilling down further into patient perspectives on the definition of successful cannulation, Fielding and colleagues state that easier needle insertion and reduced pain during cannulation— as well as the absence of pain throughout dialysis treatment—were found to be defining factors. Fielding et al
“Patients learn to survive repetitive cannulation, where feeling safe and in control can improve their experiences. This indicates cannulation is not just a technical skill, but also a social process.”
March 2022 – Issue 2
Cannulation difficulties among biggest hurdles for device-created fistulas DIFFICULTIES IN CANNULATION ARE CURRENTLY as pressing as any other challenge facing patients who undergo device-enabled arteriovenous fistula (AVF) creation for dialysis. This was a central message presented by Neghae Mawla (Dallas Nephrology Associates, Dallas, USA) at the Paris Vascular Insights meeting (PVI 2021; 21–23 October, Paris, France). Partaking in a session debating device-created fistulas— which also featured discussions on the two leading products in this space, the WavelinQ (BD) and Ellipsys (Medtronic) systems—Mawla posed the following question at the top of his presentation: Are nephrologists happy with [these] fistulas? He went on to note that, ultimately, this should be dictated by whether or not dialysis patients themselves are happy with device-created AVFs, as their interests are paramount. In the world of vascular access for dialysis, he continued, freedom from tunnelled catheters is synonymous with happiness—from patient and physician perspectives alike. Mawla also quipped that, with the odd exception, “a permanent access is a better access”, as avoiding central venous catheter (CVC) usage means reduced risks of infection, thrombosis, decreased dialysis adequacy, and other complications. Mawla stated that the two-to-three-month timeline for what he dubbed ‘phase one’ of dialysis initiation, from the patient’s initial appointment with a general nephrologist to them undergoing fistula creation, is broadly similar between surgical AVF (sAVF) and device-created AVF approaches. However, he continued, things get “interesting” when it comes to using that fistula to facilitate dialysis. “Usually, the timeframe for surgical fistulas—from first cannulation to catheter removal—is around three-to-four weeks,” he said. “And, this is generally true regardless of the anastomosis’ location.” But, Mawla then reported that this timeframe with device-created fistulas is closer to eight weeks, if not longer. “This is both device-independent and provider-independent,” he continued. “All of our device-created AVFs have the same struggles—it is just the nature of the fistula, and its physiological differences.” Mawla then informed the PVI audience that difficulties relating to cannulation at the dialysis centre are a crucial contributing factor in this increased timeframe and subsequent delays in fistula usage. “If we are going to talk about unhappiness from a device-created AVF perspective, our focus should be here, because the patients get frustrated, the dialysis staff get frustrated, and then ultimately the nephrologists get frustrated as well,” he added. There is very little literature on this phenomenon as things stand, Mawla continued. “Until we get past this educational hump, I think cannulation will be our holdback,” he said. “It is not screening anymore, or procedural techniques. There is still the issue of maturation, but I think cannulation is a bigger problem.” He further noted that a key, short-term advantage of device-based AVFs over sAVFs—the fact the former can be performed by interventional nephrologists at their centre, without the need for increased timelines and additional appointments—is somewhat lost if Neghae Mawla the patient is referred to a vascular access surgeon to undergo the procedure. Mawla did also touch on some of the other key benefits held by device-created fistulas, including their longevity as functional dialysis accesses—citing patients at his centre who no longer require follow-up more than five years on from their creation procedure because “they are doing so well”. He also pointed to the fact that patient satisfaction is “clearly very high”, as per several major studies, when it comes to device-created AVFs—largely due to the operating techniques used and associated cosmesis. “In summary, it is about setting appropriate expectations for happiness,” Mawla concluded. “For nephrologists, it is really about understanding the technology, and appropriate patient selection based on which fistula will provide the strongest dialysis option.” He further emphasised the need for dialysis staff to appreciate nuances between device-created and surgical fistulas, and the importance of making these decisions contingent on what is best for the patient as opposed to the clinician’s own preference.
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Getting It Right First Time
GIRFT report represents “call to action” and provides renewed focus for improving UK kidney disease care The Getting It Right First Time (GIRFT) national report on renal medicine represents a “call to action” for the UK renal community, and provides greater focus in driving quality improvement across care pathways for kidney disease. These were among the prominent take-home messages from an hourlong webinar that took place on 7 December 2021 to discuss the report’s findings and how best to implement its recommendations. “I TRULY BELIEVE THAT THIS IS THE BEST opportunity in over a decade to be able to deliver these important changes, and the GIRFT report gives a clear roadmap of recommendations for how this may be achieved,” said Graham Lipkin (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK), joint clinical lead for the GIRFT report on renal medicine. He noted that the report, which was published in September 2021, centres on data analysis involving all 52 of the adult renal centres in England. The key finding of these analyses, in addition to insight gained from in-person visits to each unit, is that—despite there being “well-working, multidisciplinary teams of clinicians and managers, all committed to delivering excellence of clinical service” across the country—there was “widespread, unwarranted variation” between centres in terms of patient access, experiences and outcomes. GIRFT report recommendations Lipkin outlined that the national report contains a total of 18 key recommendations intended to improve NHS services for the hundreds of thousands of advanced kidney disease patients in the UK. One of the more noteworthy of these recommendations centres around increasing opportunities for patients to receive home dialysis therapies by promoting and offering these at-home options to all suitable patients—with the ultimate goal being to have at least 20% of all dialysis patients using an at-home modality like peritoneal dialysis (PD) or home haemodialysis (HHD) in every centre. Ensuring more equitable access to kidney transplantation is also among the key points outlined in the report, Lipkin stated, with the overarching recommendation here being to streamline current renal transplant pathways and reduce existing variation in both deceased and living donor transplantation. The GIRFT report’s emphasis on improved overall management of patients with acute kidney injury (AKI)—particularly regarding prompt detection and transfer—and the introduction of more definitive target rates and success measures in vascular access, were highlighted by Lipkin as well. Following this, Will McKane (Sheffield Kidney Institute, Sheffield, UK) stated that the renal community in the UK is “incredibly lucky” to have many rich sources of data, including those from the UK Renal Registry (UKRR). He also noted, however, that the GIRFT report found a lack of completeness across datasets from individual units within the UKRR, with many centres claiming their datasets were not up-to-date enough to truly support core quality improvement. A subsequent GIRFT recommendation focuses on ensuring renal centres and patients alike have timely access to contemporaneous, clinically relevant outcome data moving forward. March 2022 – Issue 2
McKane, who is also joint clinical lead for the GIRFT report on renal medicine, asserted the importance of infection prevention and control—with particular reference to bacteraemia in HHD and peritonitis in PD receiving equal priority— before concluding that re-establishment of the National Health Service (NHS)-funded, regional Renal Networks is another key component. “The dissolution of the Renal Networks in 2014 was to the great disadvantage of renal care,” McKane said. “We see them as being a really important vehicle for improving renal care.” Implementing GIRFT in practice UK Kidney Association (UKKA) co-president Paul Cockwell (Queen Elizabeth Hospital, Birmingham, UK) kicked off a subsequent roundtable discussion by noting that—based on feedback from a number of UK renal centres—Lipkin and McKane’s supportive efforts have already made an impact on both the clinical and operational management sides of things. He then introduced Fiona Loud, policy director at Kidney Care UK (St Albans, UK), who asserted that “the wake-up call here is around the patient voice”. “Through many years of looking back at the way in which we have seen kidney care, that voice has not been represented enough,” she added. Loud went on to note that shared decision-making, psychological support, and available transport options and modality choices in dialysis specifically, are all “huge concerns” for patients, before echoing McKane’s point on the importance of the UK Renal Networks coming together
From top: Graham Lipkin, Will McKane, Paul Cockwell and Sharlene Greenwood
again. “But, none of this will work if we do not listen to that patient voice and if it is not acted upon,” she added. National Kidney Federation (NKF) president Kirit Modi (London, UK) followed this by claiming that, despite the profound impact COVID-19 has had on kidney disease patients in the UK over the past two years, he is currently “optimistic” following publication of the GIRFT report on renal medicine. “We have—for the first time—a fantastic and detailed report that analyses what is happening in our centres, gives us up-to-date data, and makes amazing recommendations,” he said. Modi also noted that the UK renal community’s record regarding home dialysis is poor, with many of the same issues, such as the need to increase at-home modality usage, having been around for “a long time”. “The case for home dialysis is very strong and I sense that there is a general feeling among the kidney community that it is something we should address now—which is why I was so pleased to see it highlighted as one of the key aspects within the GIRFT report.” In the discussion, Modi touched on the role the Renal Service Transformation Programme (RSTP) looks set to play alongside GIRFT—providing an appropriate introduction for Neil Ashman, clinical lead for RSTP (London, UK). Ashman stated that the two programmes are very much aligned in their goals moving forward, and detailed key RSTP targets designed to support the development of accountable strategic networks in every UK region and ensure quality, guide strategy, and continuously assess and improve care offerings. He reported that there is still a lot of work to do on this front, but that a “line in the sand” has now been drawn, with a “finished product” for implementing change hopefully being ready by April 2023. UKKA co-president Sharlene Greenwood (King’s College Hospital, London, UK) further alluded to the widespread variation identified in NHS workforces by GIRFT, adding that this is a “really important” part of the discussion— because that same workforce will be responsible for carrying out the report’s recommendations. Enhancements to the current system, and the introduction and development of new working roles, such as physician associates and consultant positions, may aid this, she stated. “This is where KQuIP [Kidney Quality Improvement Partnership] is going to be incredibly useful, as it is embedded across all of the different [renal] networks that have re-emerged, and I think we need to be supporting our local workforces to be able to deliver on all of these great ambitions,” Greenwood said. Rachel Gair, KQuIP programme lead at the UKKA (Exeter, UK), agreed with Greenwood, asserting that KQuIP is “dependent” on a workforce that is skilled in quality improvement (QI). “So many units are doing QI—and doing it really well—but we have to understand that change does not happen in isolation,” she claimed. Gair also stressed the importance of workforces being upskilled and also celebrated, particularly at a time when NHS staff are severely fatigued due to the pandemic, with information sharing between centres and data usage being key in this process. Fittingly, the webinar discussion was closed by Tim Briggs, chair of the GIRFT programme (London, UK), who reiterated Loud and Modi’s points on the importance of shared decision-making and patient involvement. “I think we now have a focus on how we can drive quality improvement going forward,” Briggs concluded.
Key recommendations from the report include: stablish NHS-funded, regional renal networks to ensure quality and efficiency of care, monitor service E effectiveness, embed sustainable kidney care and accountability for service delivery. nsure that patients predicted to reach end-stage kidney disease within 18 months are fully assessed in E advanced kidney care services and are offered all possible care options. Ensure that access to a comprehensive renal conservative management pathway is available to all patients. treamline renal transplant pathways to increase access and reduce unwarranted variation in deceased S and living donor transplantation. educe variation in incident and prevalent definitive haemodialysis vascular access rates and deliver R Renal Association clinical practice guideline minimum thresholds (60% incident and 80% prevalent patients with arteriovenous fistula or graft). nsure home therapy is promoted and offered for all suitable dialysis patients and that a minimum E prevalent rate of 20% is achieved in every renal centre.
Charing Cross Symposium
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CX 2022 CX Masterclass to examine non-dialysis vascular access functions
Challenges in fistula creation to take centre stage during Charing Cross symposium
A SESSION AT THE UPCOMING Charing Cross symposium (CX 2022; 26–28 April, London, UK, in-person and virtual) will examine a wide range of alternative vascular access functions beyond dialysis, including thrombotic disorders, hyperlipidaemia, neurological diseases, and others. CX executive board members and co-chairs of the event’s vascular access section Nicholas Inston (Queen Elizabeth Hospital, Birmingham, UK) and Domenico Valenti (King’s College London, London, UK) will moderate proceedings. “Erythrocytes and plasmapheresis can improve long-term outcomes in patients with sickle cell disease and some neurological conditions,” Valenti told Renal Interventions. “A permanent vascular access with central line is required to deliver such treatments, but can be difficult to obtain in these patients. And, creation of an arteriovenous fistula has been suggested as an interesting alternative to central lines— but, unfortunately, its routine application is supported by limited evidence. “This year at CX we are proposing this uncommon topic, which has never been presented before in any vascular access meetings, for our Masterclass session. I am sure this topic will generate a lot of discussion, and the delegates can share their experience and expertise. CX is the perfect platform to explore the possibility of creating a worldwide, multicentre registry about this specific topic.”
This year’s Charing Cross symposium (CX 2022; 26–28 April, London, UK, in-person and virtual) will kick off with a series of presentations and discussions on several key ways to improve vascular access outcomes, primarily for dialysis. A series of vascular access workshops (26 April) and the Vascular Access Masterclass portion of the CX programme (27 April) are set to feature multiple technologies designed to promote arteriovenous fistula (AVF) maturation—something that is integral to kidney care physicians’ attempts to provide suitable haemodialysis access options for their patients.
Nicholas Inston (left) and Domenico Valenti
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ne such technology is a wearable device that initial resistance in terms of acceptance for [Amplifi], with promotes usable fistula creation via presurgical people asking why they should use it if they already know vein dilation, the FA-1 (Fist Assist Devices). This the access is going to work. innovation received US Food and Drug Administration “But, we know there is a certain amount of access (FDA) Breakthrough Device failure, and if you are going designation late last year to take this failure rate out of FA-1 following the announcement the system, then I do not see a of positive results from the downside in using this device in company’s global FACT trial in all patients. It is all ‘plus-plus’ August 2021. because you know the vein Speaking to Renal Interdilates, and if the dilated vein is ventions, Fist Assist CEO and used for access creation, it will founder Tej Singh said: “It is be available for use earlier—as an exciting time for the global opposed to creating an access commercial launch of the novel upfront and, one or two weeks Fist Assist device. After successdown the road, realising it is ful completion of the FACT not going to work.” trial and the recent FDA BreakElsewhere in the same through Device designation, session, Jeremy Crane (Imperial the Fist Assist device is well-poCollege Healthcare NHS Trust, sitioned to help many patients. London, UK) is going to outline “In Europe, the device is CE-mark approved for vein the importance of vein preservation in bettering fistula dilation and AVF maturation. In the USA, it has a novel outcomes for dialysis patients, and assess the feasibility FDA approval for arm massage and to increase arm circu- of this approach in clinical practice. lation to compressed areas. Arm vein wellness will change “[The topic of vein preservation] is significant because, with Fist Assist globally!” when vein preservation is practised correctly, it Another novel technology in this space, the makes such an affirmative difference in outcomes Amplifi vein dilation system (Artio Medical), will for patients needing a successful fistula,” Crane also be showcased by Surendra Shenoy (Washsaid, speaking with Renal Interventions. “And in ington University School of Medicine, St Louis, turn, this can lead to a better quality of life on USA) at CX 2022. Amplifi is designed to stimulate dialysis.” arm vein enlargement prior to fistula creation Surendra Shenoy Discussions revolving around Gracz AVFs, in order to improve eligibility for AVF surgery, an app intended to aid clinicians in the decireduce maturation timelines, and increase rates sion-making process for selecting an access of successful maturation. option, and pharmacological strategies for boostShenoy, who also presented “encouraging” ing fistula maturation, as well as the cardiovascuresults from a first-in-human study of the device lar complications that stem from access creation in November 2021, told Renal Interventions: “I and usage, are also set to feature prominently think what is going to happen is there will be an Jeremy Crane during the vascular access programme.
Podium first presentations involving drug-eluting balloons to headline at CX 2022 ONE OF THE MOST PROMISING YET divisive topics regarding dysfunctional dialysis access, the use of drug-eluting balloons, will feature prominently at the Charing Cross symposium (CX 2022; 26–28 April, London, UK, in-person and virtual). As part of the event’s vascular access programme, Andrew Holden (Auckland City Hospital, Auckland, New Zealand) is
set to present 36-month results from the IN.PACT AV Access trial (Medtronic) for the first time. This follows Holden’s podium first presentation at CX 2021, which saw him relay the “outstanding” 24-month target-lesion primary patency rates and “highly significant advantage” over standard balloon angioplasty procedures offered
by Medtronic’s IN.PACT AV drug-coated balloon (DCB). Elsewhere during this year’s iteration of the CX symposium, another podium first presentation will see an update from Tjun Tang’s (Singapore General Hospital, Singapore) group on the ISABELLA pilot study (MedAlliance), discussing 12-month results on the safety and efficacy of the company’s Selution sustained limus release (SLR) sirolimus-eluting balloon for endovascular salvage in patients with failing arteriovenous fistulas. In addition, Kate Steiner (East and North Hertfordshire NHS Trust, Stevenage, UK) will discuss usage of a plain balloon angioplasty first, and a drug-eluting balloon
second, in vascular access maintenance. “We really want to tackle all the things that are at the cutting edge of clinical practice in vascular access,” Nicholas Inston told Renal Interventions, discussing this portion of the vascular access programme ahead of CX 2022.
Issue 2 – March 2022
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Profile
Q&A
Charmaine Lok Equally at home on the ward seeing patients, at study sites conducting research, and travelling the world for voluntary medical missions, Charmaine Lok has engaged in all aspects of the modern medical profession. Lok is a nephrologist and clinician scientist at the University Health Network (UHN), and professor of medicine at the University of Toronto, in Toronto, Canada. As the principal investigator of the pivotal trial that made endoAVF accessible to patients in North America and chair of the Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for vascular access, she has also played a central role in shaping the current landscape of kidney disease care. Here, Lok speaks to Renal Interventions about these achievements, her career to date, and more.
Fact file Current appointments: Professor of medicine, University of Toronto, Toronto, Canada Nephrologist and clinician scientist, University Health Network, Toronto, Canada Graduate Faculty, Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto Graduate Faculty, Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Canada
Education: 1995: MD, McMaster University 1998: Diplomate, American Board of Internal Medicine, Philadelphia, USA 1999: FRCP(C), Internal Medicine, Royal College of Physicians and Surgeons of Canada, Ottawa, Canada 2000: FRCP(C), Nephrology, Royal College of Physicians and Surgeons of Canada
What initially attracted you to medicine, and the field of nephrology in particular? Interestingly, I was not initially attracted to medicine but it fell along a path that led me to realise: never say “never”. When I struggled to decide between a career in architecture or physical therapy, family and friends offered another option. “What about being a doctor?” I said “never”. I became a physical therapist and worked as one for several years. I loved it, but knew I would become restless for greater challenges and pursued a career in medicine. Later, I could not decide on a medical subspeciality. When asked about nephrology, I said “never”, but then realised nephrology encompassed cardiology, respirology, rheumatology, intensive care and much more. It was so ridiculously complex and confusing it would take my entire life to try to figure out, and there was so much potential for therapeutic discovery that it would keep me busy, excited and challenged. Further, because kidney disease is largely silent—patients often come to our attention at a late stage or when it is too late—I wanted to help make a change in this process and their lives, and to lend a voice to advocate for kidney patients and their families. March 2022 – Issue 2
Who have your mentors been and how have they impacted your career? I am so grateful to have had many mentors and role models in my life both personally and professionally—too many to name them all, and all of them patient, kind and so wise. Focusing on my nephrology and research career, Robert Richardson supported my inquisitive nature to find the answers to challenging clinical questions; he mentored and encouraged my leadership in haemodialysis and I followed in his footsteps as a medical director. I was inspired and encouraged by the legendary nephrologist Dimitrios Oreopoulos, who conceived peritoneal dialysis, to innovate; I was the first nephrologist to create an endoAVF in an animal model and led the way for the innovation to be used in humans as the principal investigator in the pivotal NEAT trial. I am also thankful for the endless support and advice from my early mentors, Jan Hux, Kenneth Stanley and the renowned David Sackett, and the guidance of visionaries including Catherine Whiteside, Stan Fenton, Paul Tam, Jerry Yee, Harold Feldman, Marc Glickman and Gerald Beathard. A career highlight I will cherish is my meeting with Michael Brescia—creator of the arte-
2001: MSc, Clinical Epidemiology, Harvard School of Public Health, Boston, USA
Honours (selected): 2013: Gerald Beathard Award, American Society of Diagnostic and Interventional Nephrology 2015–present: Principal investigator, PISCES study 2016–present: Chair, KDOQI Vascular Access Guidelines 2016–present: Associate editor, American Journal of Kidney Diseases 2019: Garabed Eknoyan Award, National Kidney Foundation
riovenous fistula (AVF) for haemodialysis—who affirmed my pivotal research. What do you feel has been the most important development in the field of kidney care during your career? There is not a single most important development, since the field of kidney care is so broad. In the context of chronic kidney disease (CKD) care before dialysis, progress in the management of diabetic kidney disease and cardiovascular prevention—for example, wearable insulin pumps and glucose monitoring, ACEI/ARB, and SGLT2-inhibitors—have helped patients survive to progress to end-stage kidney disease (ESKD) needing dialysis or transplant. Once on dialysis, erythropoietin-stimulating agents, which we take for granted now, were transformational for improving patients’ quality of life and reducing blood transfusions. For the Achilles’ heel of haemodialysis—the vascular access—endovascular fistula creation has been the most important development to increase options for patients. Why was the most recent update to the KDOQI guidelines needed, and how would you assess the impact it has had? Since the last KDOQI vascular access guidelines in 2006, there have been new practice patterns, technologies and more rigorous evidence to inform vascular access care. An update was certainly due. The benefits of a long timeframe between guidelines are the ability to observe and understand practice impacts from prior guidelines, accrue data from new studies, and revise guidelines accordingly. Importantly, the targets and emphasis of the 2019 guidelines have changed from being more population-based to an individualised vascular access approach to care. As such, the impact should be measured accordingly. Additional key impacts will be the new research and data stimulated to inform the next guidelines. Besides your own work, what is the most interesting piece of nephrology research you have seen in the past year? The most interesting and exciting research over the past year is the proof-of-concept pig organ xenotransplantation that occurred at NYU Langone Transplant Institute in October 2021. In this study, a kidney from a genetically engineered pig was anastomosed to blood vessels in the upper leg (designed to be external for observation purposes) of a person on life support with no detectable brain activity, which immediately produced urine. Clearly, further rigorous, long-term research and serious ethical considerations must occur, but this may be a significant gamechanger for ESKD patients in the environment of organ shortages for kidney transplantation. What is the most significant unmet need in the kidney care field right now? On a global stage, CKD awareness and strategies for prevention. For potential kidney transplant patients, availability of organs and access to immunosuppressive agents to maintain the transplanted organ. For dialysis, treatments that effectively target cardiovascular events and sudden death, and, of course, our Achilles’ heel— achieving reliable, complication free vascular access without needless interventions.
Profile
Charmaine Lok with Michael Brescia
Illustration by: Andy Watt / NB Illustration
Could you outline your medical mission to Africa, and how it has impacted your career as a physician? The medical mission I took part in was to Tanzania in 2008—our homebase was in Moshi, where we set up a clinic, Pamoja Tunaweza Women’s Centre. Our focus was to help women and children with HIV, although within the clinic and on our caravans to surrounding areas, we treated many men, women and children without HIV too. From a nephrology perspective, I tried to help by donating equipment automated to detect urinary abnormalities and an electrocardiogram (ECG) machine, in an effort to screen for CKD and its complications. There was no access to haemodialysis but we did arrange for a patient to receive acute peritoneal dialysis. At the end of the mission, we climbed Mount Kilimanjaro to raise funds for the clinic. It was exhilarating to reach the top, but it was even more gratifying that we raised enough to keep the clinic open for two or more years. This experience was tremendously humbling and remains a poignant reminder of the stark contrast to my privileged work and life environments. Perhaps it has influenced me to continue to do volunteer work, such as for the
“For the Achilles’ heel of haemodialysis—the vascular access—endovascular fistula creation has been the most important development to increase access options for patients.” National Kidney Foundation (NKF), American Society of Nephrology (ASN) and other organisations, and to set up my own non-profit organisation, Kidney CARE Network International, to help patients living with CKD. What advice would you give to people embarking on a career in the field of nephrology? Make sure you are happy with what you are doing. Be ready to work hard, be ready for surprises, take opportunities as they come (never say never!), and have resilience and patience, as you
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will come across some of the most complex medical/surgical cases, and difficult patients and families, in your career. But you may also be rewarded with the deep gratification of being the person to provide or guide the life-changing treatment to positively change the life of a kidney patient who desperately needs your help. Be ready for the future, as it is prime time for the kidney world to experience innovation and change. What are your interests outside of the field of medicine? My interests outside of medicine include my adventures with horses and the equestrian sport—I ride dressage, although I also love to hack and have previously jumped courses. I am currently challenged by training a young horse and constantly learning to be a better horsewoman. Also, after a long hiatus, I have picked up the paintbrush and started painting again. I love nature and spend hours putzing about and enjoying my pond, hiking, and the great outdoors. My driving force is my family; my two beautiful daughters are my greatest pride; my comfort is my dog, Belle; and I am supported by my incredible husband. Issue 2 – March 2022
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Small Renal Masses
Interventional Radiology
Shifting paradigms in diagnosing and treating small renal masses In light of recent and upcoming developments in the space, Vinson Wai-Shun Chan and Tze Min Wah (Leeds, UK) explore the evidence and latest progress in renal tumour biopsy (RTB), and discuss the treatment of small renal masses (SRMs) more broadly.
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he optimal diagnostic pathway and treatments for small renal masses (T1N0M0) is controversial. Due to the lack of tumour markers and inability to determine malignancy from benign pathologies, SRMs are often overtreated. Yet, RTB has not been widely implemented into the diagnostic pathway of SRMs. In terms of treatment, partial nephrectomy remains the gold standard for curative surgery but is associated with significantly reduced renal function and high complication rates. Although high-quality evidence is lacking, percutaneous image-guided ablation (IGA) provides excellent oncological, perioperative, and renal function outcomes. As a result of increased used of abdominal imaging, the rates of incidentally discovered SRMs have increased over the past decade. However, there is no reliable imaging or tumour markers to determine the lesion’s malignant potential. Further, it was shown that over 20% of these treated masses are benign in histology, suggesting significant overtreatment of patients without malignant disease. A systematic review and meta-analysis have reported that diagnostic core biopsies have a sensitivity and specificity of 99.1% and 99.7%, respectively, for malignancy. Despite the proven accuracy and safety profile of RTB, there is reluctance to implement RTB within the urological community. The benefits of performing RTB before treatment is at least twofold. First, this can guide patient decision-making on whether to receive treatment. More than 90% of interviewed patients with SRMs have expressed that they believe knowing the mass’ histology status will aid decision-making for the optimal treatment. Secondly, given a malignant result for RTB, an RTB can guide the best treatment for the patient, where low-grade SRMs could opt for active surveillance or IGA; and high-grade SRMs could opt for partial or radical nephrectomy. In fact, the latest study of the EuRECA registry1 showed that, amongst patients undergoing ablation, the pre-cryoablation biopsy rate rose from 42% in 2015 to 72% in 2019
March 2022 – Issue 2
(p<0.001). Subsequently, patients are less likely to be overtreated for benign disease when more biopsies are performed (odds ratio [OR]=0.64, p<0.001). This has shown promising potential in extending the use of preoperative RTB to other forms of SRM treatment—especially partial nephrectomy—avoiding the significant decline in renal function and high complication rates post-nephrectomy. However, it is important to stratify patients who will benefit the most from biopsies. For example, patients
(IRE).2 The advantages of IGA compared to partial nephrectomy are at least twofold. Firstly, IGA is significantly less invasive compared to partial nephrectomy, with significantly reduced complication rates.3 Secondly, IGA is associated with a significantly lesser drop in renal function, which is crucial in patients with bilateral (synchronous or asynchronous) disease, or those who require repeat treatments— such as Von-Hippel Lindau syndrome (VHL) patients. However, there is a lack of high-quality evidence to support the oncological non-inferiority of IGA compared to partial nephrectomy. This could be due to a few reasons. Firstly, previous recruitment of various trials involving IGA has failed, notably in the SURAB and the CONSERVE studies, which could be a result of patient preferences and lack of evidence at the time to support the recruitment process. Secondly, as pointed out by a review performed by the European Association of Urology (EAU) Renal Cancer working group, the quality of observational studies and systematic reviews on the area is poor, notably affected by severe selection bias whereby younger and fitter patients tend to receive partial nephrectomy, compared to old and frail patients receiving IGA. Similarly, the latest systematic review and meta-analysis, published in the International Journal of Surgery, has suggested the same.3 Based on the limited quality of evidence on T1a SRMs, ablation is associated with similar cancer-specific survival, metastasis-free survival and disease-free survival compared to partial nephrectomy. Local recurrence-free survival is
Vinson Wai-Shun Chan
RTB can act as index tests for future diagnostic studies to facilitate development of new imaging modalities. For future interventional studies of new treatments, RTB will also allow focused research on RCC, rather than undifferentiated SRMs alone to improve the quality of evidence. Secondly, studies reporting outcomes from interventional oncology studies must conform to the CONSORT guidelines to allow for meta-analysis and further discussion of the data. Finally, urologists and interventional radiologists should work closely together to embrace and produce optimal outcomes for patients presenting with RCCs. Upcoming results from the NEST trial comparing the effectiveness of nephron-sparing surgeries and future research studies are highly anticipated. References: 1. Chan V W-S, Keeley F X, Lagerveld B et al. The changing trends of image-guided biopsy of small renal masses before intervention—an analysis of European multinational prospective EuRECA
“Urologists and interventional radiologists should work closely together to embrace and produce optimal outcomes for patients presenting with renal cell carcinomas.” over the age of 70 or who are unfit to undergo definitive treatment for SRM may not benefit from RTB; while those with complex tumours or comorbidities may benefit from RTB to prevent complex, high-risk treatments in these patients.1 Since the introduction of image-guided radiofrequency ablation (RFA) in 1998, the technology of IGA has developed significantly to include multiple different energy sources including cryoablation, microwave, and irreversible electroporation
Tze Min Wah
similar to partial nephrectomy patients with a follow-up of more than five years.3 Patients undergoing ablation also experience significantly less postoperative complications (risk ratio [RR]=0.72, p=0.02) and significantly smaller decline in renal function postoperatively (mean difference [MD]= -7.42, p<0.01). Similarly, the long-term outcomes at our centre from 2003 to 2020 have shown similar outcomes, with overall survival, cancer-specific survival, local-recurrence free survival and metastasis-free survival in IGA at least as good as partial nephrectomy, with significantly better renal function preservation.4 Specifically, IGA is of use in patients with Von-Hippel Lindau syndrome—shown in the 17 patients who underwent IGA for VHL-associated renal cell carcinoma (RCC) and experienced excellent oncological outcome without the need for renal dialysis over 10 years of follow-up.5 The role of RTB and IGA has developed significantly throughout the last two decades; however, further research is required to consolidate the role of RTB and IGA in the treatment of SRMs. Firstly, RTB needs to be implemented in both research and clinical pathways.
registry. Eur Radiol. 2022; 5:1–12. 2. Wah T M, Lenton J, Smith J et al. Irreversible electroporation (IRE) in renal cell carcinoma (RCC): a mid-term clinical experience. Eur Radiol. 2021; 31:7491–9. 3. Chan V W-S, Abul A, Osman F H et al. Ablative Therapies versus Partial Nephrectomy for Small Renal Masses—a systematic review and meta-analysis of observational studies. Int J Surg. 2022; 97:106194. 4. Chan V, Osman F, Cartledge J et al. Percutaneous image guided cryoablation and radio-frequency ablation versus partial nephrectomy for small renal cell carcinomas: A ten-years, single centre observational study. J Urol. 2021; 206(3): 770–1. 5. Chan V W-S, Lenton J, Smith J et al. Multimodal image-guided ablation on management of renal cancer in Von-Hippel-Lindau syndrome patients from 2004 to 2021 at a specialist centre: A longitudinal observational study. Eur J Surg Oncol. 2021. Doi: https://doi.org/10.1016/j.ejso.2021.10.022.
Vinson Wai-Shun Chan is a final year medical student in the School of Medicine in the Faculty of Medicine and Health at the University of Leeds in Leeds, UK. Tze Min Wah is a professor, and senior consultant diagnostic and interventional radiologist, in the Department of Diagnostic and Interventional Radiology in the Institute of Oncology at St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, in Leeds, UK. The authors declared no relevant disclosures.
Ureteric Stents
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Interventional Radiology
New technologies in malignant ureteric obstruction Malignant ureteric obstruction (MUO) poses several tangible threats to cancer patients—and these threats translate, in turn, to challenges for the interventional radiologist and other treating physicians. Here, Conrad von Stempel and Tim Fotheringham (London, UK) describe a number of alternative techniques to common approaches via percutaneous nephrostomy (PCN) or with polymeric JJ stents, while also assessing currently available evidence in this space. URETERIC OBSTRUCTION IS A COMMON sequela of genitourinary and other malignancies. Patients with MUO have a poor overall prognosis, with a median life expectancy of <12 months. MUO is a feature of advanced cancer and progressive bilateral obstruction leads to irreversible deterioration of renal function. The development of MUO may also preclude chemotherapy and other cancer therapies. A multidisciplinary approach in the management of MUO patients is required, as treatment selection is dependent on the prognosis of the patient, and the patient’s performance status combined with available cancer treatment options. Although some MUO can be treated with a retrograde approach, many patients require an antegrade approach by an interventional radiologist. MUO is commonly treated with PCN or polymeric JJ stents—however, there are other management options available. Permanent PCN may be required when there is extensive tumour infiltration in the bladder or when the ureteric obstruction cannot be crossed. PCN drainage is a relative contraindication for chemotherapy, requires regular
exchanges, and is an undesirable outcome for most patients. Frequent tube dislodgement can occur with PCN, even when using larger-diameter nephrostomy tubes, placing the nephrostomy in a tunnel, or attempting to secure the tube with sutures and dedicated drain-fixation devices. The loop/circle nephrostomy is an alternative in such patients, using a double calyceal puncture, as it has greater security with less chance of accidental displacement and requires less frequent routine tube changes than standard PCN. If the bladder still functions, extra-anatomical stenting can be considered through a subcutaneous tunnel and suprapubic access. Extra-anatomic stenting is seldom offered in PCN-dependent patients with MUO. A dedicated device, such as the Paterson-Forrester subcutaneous urinary diversion stent (Cook Medical; 8.5Fr, 65cm) can be placed and exchanged at three monthly intervals under local anaesthetic. JJ stenting with 6–8Fr polyurethane devices fail to relieve MUO at three months in up to 51% of patients and require regular routine exchange via the retrograde route at three-to-six-month intervals. Stent primary patency is between 40% and 60% at one year. An alternative to a polyurethane JJ stent is the Resonance stent (Cook Medical), which is a metal JJ stent made from a cobalt-chromium-nickel-molybdenum alloy and has a maximum indwell time of 12 months before exchange is required. The Resonance has improved primary patency to polymeric stents in some studies with >90% patency at one year, owing to less risk of extrinsic compression and encrustation. In a systemic review, the reported migration is low, at 1%—however, stent obstruction at 17% was seen and patients are prone to
Conrad von Stempel
Tim Fotheringham
“...Selfexpanding, covered ureteric stents do appear to be more effective in treating MUO, and with better long-term outcomes, compared to JJ stents.”
Improving interdepartmental communication to avoid forgotten ureteric stents There are some very serious risks associated with forgotten ureteric JJ stents. David Maudgil (Slough, UK), outlines why and when these devices are used, as well as explaining the risks a forgotten stent might pose and providing some guidance on how to mitigate them.
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nterventional radiologists routinely place large numbers of ureteric JJ stents for a number of different indications, including ureteric blockage or ureteric injury. This is often when retrograde attempts have failed or when there is no available retrograde route from the bladder. The patients who require this come from a wide range of non-urological or nephrological specialities, particularly general surgery, gynaecology, and medicine, but will usually require follow-up and change of the stent by urologists within three-to-six months. If the stent is not removed or changed in a timely fashion, there is a high risk of encrustation of stone material around the stent, which may not only block the stent but also make it extremely difficult to remove with-
out damaging the kidney, ureter and bladder. There is also a small risk of the stent fracturing within the ureter, causing acute blockage with probable added infection. For these reasons, a forgotten ureteric stent constitutes a David Maudgil “never” event and a serious untoward incident (SUI). Although guidelines and procedures exist for routine monitoring and change of stents placed retrogradely (by urologists), we did not have a robust system for handing these patients promptly to urology for follow-up of their stent (the Healthcare Safety Investigation Branch [HSIB] report, “Unplanned delayed removal of ureteric stents”, was published in October 2020 and can be found online). We performed an audit showing that, of 50 patients in 2019 who had antegrade stents inserted (67% as emergency admissions), 40% subsequently had stents replaced retrogradely, while 45% had them removed, and 15% had extra-anatomical stenting or died before readmission. The mean time from stent insertion to plan-
the same symptoms of bladder irritation seen with JJ stents. Dedicated covered, self-expanding ureteric stents have become available, which can be inserted either retrogradely or antegradely, and offer alternatives to JJ stents requiring fewer exchanges. Devices currently available include Uventa (Taewoong Medical), which is a double-layered, coated, self-expandable metallic mesh stent. The Allium (Allium Medical Solutions) is a fully covered, self-expanding nitinol stent. The entire stent is covered with a biocompatible, biostable polymer, making it a nonpermeable tube, to prevent tissue ingrowth and early encrustation stent. The Hilzo stent (BCM) has a polytetrafluoroethylene (PTFE) cover in spiral configuration—intended to help prevent stent migration. It is designed with soft and smooth ends to minimise hyperplasia. While it is difficult to draw too many conclusions from a limited number of studies, the self-expanding, covered ureteric stents do appear to be more effective in treating MUO, and with better long-term outcomes, compared with JJ stents. Complications seen include occlusion from hyperplasia, encrustation, migration and fistulation. The cost of the devices is offset by the reduced need for reintervention as compared with JJ stents. In conclusion, there are more options for treating MUO patients beyond PCN and JJ stents. Avoiding permanent PCN is advantageous to the patient, and significantly reduces readmission for either exchanges or managing arising complications. Interventional radiologists should consider alternatives, such as extra-anatomical stents and self-expanding covered stents, when dealing with MUO. Conrad von Stempel is a consultant interventional radiologist at the University College London (UCL) Hospitals NHS Foundation Trust in London, UK. Tim Fotheringham is a consultant interventional radiologist at Barts Health NHS Trust in London, UK. The authors declared no relevant disclosures.
ning removal was 13 days, which appeared unacceptably long and increased the risk of the patient being lost to urological follow-up. These findings were discussed at a joint interdepartmental meeting and we agreed that a logbook should be kept where all antegrade stents would be recorded. Moreover, a standing item at the weekly uroradiological meeting was discussion of every antegrade stent insertion and formulation of an agreed plan for urology to follow up the patient. Subsequent re-audit three months later showed that all patients had been discussed in a timely manner, with mean interval from stent insertion to planning removal reduced to 3.3 days. It was clear that interdepartmental communication regarding these patients was much improved and that a safe system of working had been developed. This audit, with subsequent significant improvement after discussion, was presented at the 2021 British Society of Interventional Radiology (BSIR) annual scientific meeting (8–10 December; Glasgow, UK). David Maudgil is a consultant interventional radiologist at Wexham Park Hospital, Frimley Health NHS Foundation Trust in Slough, UK. The author declared no relevant disclosures.
Issue 2 – March 2022
18
Healthcare Settings
Dialysis
Houston, we have a dialysis access problem The concept of dedicated vascular access centres fuels a turbocharged Texan tussle with Karl Illig (Flow Vascular Center, Houston, USA) taking on Eric Peden (Houston Methodist Hospital, Houston, USA) in a no-holds-barred debate on how best to deliver longitudinal patient care. The question is: who will patients call with “Houston, we have a (dialysis access) problem”?
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llig tips his hat at renowned vascular access educator John Ross and “his greatest contribution”— the creation of the concept of the total dialysis access provider and total dialysis access centre. Ross’ clinical career culminated in the creation of the Dialysis Access Institute in Orangeburg in 2013, and Illig is an unapologetic advocate for similar comprehensive dialysis access centres as the model to deliver the best patient care. In a presentation titled “Dialysis access in the 21st century: A call to arms” Illig is categorical about his message to renal care physicians providing dialysis services: “You do it wrong—patients die early. You do it right—quality and quantity of life significantly improve.” His core message is that with no dedicated plan, training and staff, patients face the prospect of every event occurring in isolation, resulting in excessive catheter contact time, which leads to higher morbidity and mortality. “This is the perfect area of medicine to change care from ‘technique-driven’ to ‘problem-driven’ care,” he says. The total dialysis access centre concept to reinvent the delivery model consists of “several,
Karl Illig
March 2022 – Issue 2
overlapping and interlocking ideas: one-stop shopping for creation, maintenance, complex salvage, haemodialysis and peritoneal dialysis”. Such centres aim to draw on surgery, endovascular interventions, hybrid procedures and nephrology. This is a designed counterpoint to the accepted format of the system being geared towards “big cases”. In the main, “our patients are sick—but procedures are very low-risk,” avers Illig. “All operating rooms are set up for surgery and endo[vascular] seamlessly,” he adds. “To the nephrologist, we say: ‘just send [the patient]’. There is a near-same day service. There is no set schedule, walk-ins are welcome; we have imaging, anaesthesia, labs, clinical trials and operating rooms under the centre’s control. There is no waiting.” Longitudinal care sits at the heart of such centres that only provide dialysis care. Illig notes that there is a sense of a plan for all patients that includes recognising when plan A is not working and identifying when maturation is taking too long. “Of course, the devil is in the detail. How can you do this in a cost-effective manner? At the end of the day, your income must meet your expenses,” he says.
In favour of comprehensive centres Peden’s riposte is that the most beneficial aspect to practising in a hospital system is that you can provide truly comprehensive care. “No matter how sick the person, no matter what their other medical troubles are, there are additional resources available at the hospital setting that are simply not available at some outpatient settings,” he states. Peden acknowledges that freestanding centres offer a variety of advantages for what he terms “garden variety” vascular access care. “In the hospital setting, we are certainly not as limber as the freestanding access centres, which are set up to provide same-day service. For some emergent procedures, such as clotted fistulas or grafts, I think it is better for patients to go to a freestanding centre because the convenience factor is impossible to overcome. For standard creations, I think that is probably reasonable as well, but if there is a bleeding complication, or a person needs transfusion, then you probably need to be in a bigger facility,” he continues. “In other scenarios, when things are more complicated—when patients have potassium
“AV [arteriovenous] access in most places is a low-priority operation, including at universities that I have been affiliated with. It brings to mind surgery at midnight— you get bumped by everybody else.” Karl Illig issues, or heart issues such as rhythm problems, or any other serious conditions that dialysis patients have—then care really cannot be provided safely at the access centre. Heaven forbid there are complications, those really need to be managed in a hospital,” he says. His argument relies heavily on the point that a tertiary care hospital is capable of providing heart-lung support or “whatever is needed”. Other complications, such as bleeding, clotting or embolus, are also very difficult to manage if providers do not have access to full surgical facilities, or additional equipment or tools like snares, embolectomy catheters and surgical techniques that can be provided in a hospital operating room or interventional suite that may not be available at a freestanding centre. “Many freestanding centres do not have covered stents, which is probably an error because if they have rupture and bleeding, those things have to be dealt with—occasionally with a stent graft,” Peden adds. “If all you can do is put a balloon up, that is a problem, because it means patients are eventually sent to a hospital or clinic, such as where I work, and then we take care of it through the emergency room and operating room. The question is: what degree of complexity does the person need to have that they might need more support? “My focus is complex access. So, I take care of a lot of complicated patients that need big, extensive revisions that I think would be really challenging to do in standalone dialysis access centres. At the hospital, we are able to offer more definitive care. A great example is someone I am treating who has had angioplasty upon angioplasty every few months for stenosis of the
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Dialysis central venous lesion. To alleviate the thoracic outlet compression, we might surgically remove a rib or clavicle, reconstruct the subclavian vein and fix the aneurysm, but that could turn into a much bigger deal that simply cannot be offered in access centres. There are some bigger and more complicated procedures that definitely need to be done in surgical programmes like mine.” Illig responds to underscore that, at Flow Vascular, operations are performed in an (arteriovenous access-only) hospitaI, and that their office-based labs are used for office visits and “very straightforward” elective fistulagrams. Both agree that for a fairly clear-cut, urgent procedure, a freestanding dialysis access centre is probably the most convenient first port of call for patients, all the way from simple things, such as parking, to path to care and speedy treatment being easier to navigate than in a hospital setting where the logistics and requirements can be substantial, especially in the COVID-19 era. Further, access centres plan for same-day evaluation and procedure, whereas there are generally days or weeks between the two in a hospital setting. Multidisciplinary care Illig is insistent that at freestanding dialysis centres “we all take care of all patients, and communication is key”. He further asserts: “There are well-trained physicians who want to be there and do this. The care delivered is based on a high degree of standardisation and skill arising from repetition. Academic and educational focus takes centre stage, and the same team is in the operating room every day.” This enables surgeons, interventionalists and nephrologists “all working truly together in one place—not just paying lip service from each separate office”. The key issues other than interdisciplinary decision-making are same day service (or close to it), getting everything needed in one step on one day, and zone defense, where all patients are cared for by the team at hand rather than waiting for “their” person. Such centres, Illig offers, also “allow for control of your own procedure space, which is, incidentally, set up for both surgery and endovascular intervention in all cases. We just do what is best for the problem at hand rather than what we happen to have a certificate on the wall for”. Peden aims to land a direct hit when he notes that, barring a few well-run freestanding access centres, many do not have multidisciplinary teams on hand. “There are centres with just vascular surgeons performing both open and endo procedures. So, although they carry out both types of procedure, I am not sure that is a multidisciplinary conversation unless you are talking to your ‘endo’ self and your ‘open’ self, back and forth. Of course, there are some centres where transplant, surgery and radiology work really well together and provide comprehensive care. But many vascular surgeons of my generation and younger provide the full gamut of treatments and usually do most of the work themselves,” he notes. Outcomes Another pertinent question is: does setup have a bearing on outcomes? According to Illig, it does. “A recent audit of 671 cases reviewed over a six-month period showed that overall infection rate was 2.7% and serious infection rate was 0.6%,” he reports. In addition, the mortality rate was found to be 0.5% (including one self-withdrawal), results for arteriovenous fistula 30-day patency rate (not maturation) were as follows: radiocephalic=100% (n=4); brachio-
Eric Peden
“No matter how sick the person, no matter what their other medical troubles are, there are additional resources available at the hospital setting that are simply not available at some outpatient settings.” Eric Peden
cephalic=95%; brachiobasilic first stage=89%; brachial vein transposition second stage=89% (77% overall); brachial vein transposition single stage=82%. Illig notes: “They also placed 24 HeRO grafts (Merit Medical) with a 30-day patency of 94% and a 30-day infection rate of 4%. The Flow Vascular team also placed 37 peritoneal dialysis catheters with a 30-day function rate of 96%. The centre also recorded catheter prevalence rates of between 4% and 9%.” Peden weighs in to say that the results from his hospital “are similar”—but warns against easy comparisons. “Complication rates might actually be higher in a centre like mine only because the low-hanging fruit in terms of the easier procedures in healthier patients are being done in freestanding centres, and more complicated procedures, such as in a stroke victim on oxygen and anticoagulation-dependence—those things come downtown,” he says. He also counsels against assuming the catheter prevalence rates from Flow Vascular are indicative of all freestanding centres. “I think [these rates] are really dialysis centre-to-dialysis centre-dependent and are heavily influenced by how that centre is run, and the referral patterns they have. The numbers you say are good and should be what people are trying to achieve i.e., less than 10% catheter rates.” Leftover surgery at midnight Illig maintains that dialysis access deserves more respect; “other than venous disease, it is the most common problem our patients have. AV [arteriovenous] access in most places is a low-priority operation, including at universities that I have been affiliated with. It brings to mind surgery at midnight—you get bumped by everybody else. Typically, it is the junior resident helping out as nobody else wants to do it and care received can be speciality-driven, with usually only surgical options available.” Peden counters sharply by stating: “Of course, Friday at five, where is the person going to go? If they are knocking on the access centre door, they are going to be knocking for a while because nobody is coming until Monday morning. Whereas we are available 24/7, right? This weekend, my partner was doing thrombectomies all weekend, followed by temporary catheter placement for urgent dialysis, because those problems happen.”
To the specific charge of surgery at midnight, Peden replies: “I might say better midnight than Monday morning! Because, in many access centres, patients are going to be given a bottle of kayexalate and told ‘good luck over the weekend, see you on Monday morning’, which is a real problem. In my centre, we have two operating rooms dedicated to dialysis access, every day, Monday through Friday, and for emergencies as they arise at the weekend.” But, he agrees there is legitimacy to the allegation of being bumped. “Of course, there are other hospitals where access is not really a primary focus. For sure, patients are going to have to wait until all the gallbladders, hearts and traumas are done, which sometimes means a patient is waiting for days and days to have the procedure…that is clearly not a service to the patient. And that is why, if it is straightforward, going to an access centre—where that is their focus—is helpful.” Established systems best serve dialysis patients Peden’s memo to colleagues reads: “Honestly, dialysis patients are best cared for where there is a system in place, so the two scenarios of access centre and hospital-provided care do not have to be exclusive. I work with lots of people at access centres. I will absolutely send patients to access centres if they need a catheter exchange or such like, which can be quickly treated. They really like coming to these centres and the swag they provide. “And then, if there are more complications, they will come back and see me, or if they have a preference for more anaesthesia or more sedation. So, the two do not have to live in exclusivity or competitive spirit. I think there are many sick people out there who need as much help as they can get and both places can provide good care. But I think there will always be a role for big facilities like mine to help take care of people with more complicated troubles.” Peden and Illig both sign up to the view that patients are best served by a team taking care of people with dialysis needs as efficiently as possible, and concede they simply emphasise different strategies of war to achieve the same goal. The essential principle, they agree, is that everyone involved in dialysis access should take it seriously and “be access whisperers. Remember, doing it right saves lives”.
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Percutaneous vs Laparoscopic PD Surgery
Dialysis Modified Seldinger technique provides option for safe, immediate access to peritoneal dialysis
“M
odified Seldinger PD [peritoneal dialysis] with ‘urgent start’, in my view, is the safest way to place a PD catheter, and I think it will dramatically change how units manage end-stage kidney disease [ESKD] and how they run their dialysis service,” Jan “John” Swinnen (University of Sydney/ Westmead Hospital, Sydney, Australia) informed audiences at the Controversies in Dialysis Access (CiDA) meeting (11–12 December 2021; Dallas, USA). Swinnen presented this viewpoint on his preferred method for establishing PD—‘urgent start’ Seldinger PD (USSPD)—during a session on home dialysis modalities, stating that it can enable treatment to begin in as little as 24 hours. He began by noting that there are four major modalities in the treatment of ESKD—haemodialysis, PD, renal transplantation and medical management—but that PD is “much underused” across the globe. Alongside open, laparoscopic and peritoneoscopic surgeries, the
Seldinger technique is one of four overarching ways to place a catheter for PD, he continued. Swinnen further stated that he has worked to increase usage of the USSPD technique—a blind yet less traumatic method—at Westmead Hospital in an effort to decrease the number of patients starting dialysis with a Vascath central venous catheter (CVC). On top of this reduction in Vascath deployment and its associated complications, Swinnen relayed additional benefits with USSPD, including the fact there is no need to wait for arteriovenous fistula (AVF) maturation, nor any need to wait for surgical healing as with open or laparoscopic approaches. Swinnen added that it can be readily done under local anaesthetic, plus a minor sedation, and in “virtually anyone”, including the sickest patients, and obesity and full anticoagulation are not contraindications to the procedure. Preservation of residual renal function is another advantage of USSPD, he said, which is “a very important point that escapes a lot of access surgeons”. “I believe that modified Seldinger PD is an essential tool for the endovascular fistula surgeon,” Swinnen continued. “It is a get-out-of-jail-free card when the patient has intractable steal syndrome, or impaired cardiac function and a high-flow fistula, or if they have an occluded fistula with no other good options.” He added that this technique is an endovascular procedure requiring high-grade ultrasound to guide the initial puncture, radiological imaging, a “good range” of endovascular equipment, and also reverse mapping of the catheter—all of which are familiar to endovascular fistula
Advanced laparoscopic technique carries no technical contraindications for peritoneal dialysis
Frank Dor
Laparoscopic surgery should be preferred to open and percutaneous approaches when it comes to placing a peritoneal dialysis (PD) catheter—but the technique used pales into insignificance against the need for multidisciplinary, dedicated teams overseeing this process. That is according to Frank Dor (Imperial College Healthcare NHS Trust, London, UK), who chaired the committee behind the 2019 International Society for Peritoneal Dialysis (ISPD) guideline update on optimising PD access in adult patients.1 DOR IS A STRONG ADVOCATE FOR PD IN patients requiring renal replacement therapy. Speaking to Renal Interventions, he cites increased freedom due to its home-based nature, preservation of urinary output, lessened negative impact on cognitive function and cardiovascular factors, and reduced costs, as key benefits versus haemodialysis. However, the place for PD in this care pathway is uncertain—haemodialysis is often ‘the default’, while pre-emptive live donor kidney transplantation represents ‘the ideal’. According to Dor, PD is currently underutilised and is “very dependent on relatively few enthusiasts globally”, with mixed uptake rates being seen between geographies due to cultural differences and funding discrepancies. He notes that there are currently two major techniques for PD catheter placement: surgical methods, such as advanced laparoscopy or an open operation, under general anaesthetic, and percutaneous approaches, such as the Seldinger technique, under local anaesthesia. Dor believes laparoscopy is the best of these options, not least because increased visibility enables the whole abdominal cavity to be inspected, and it makes possible adjunctive procedures like rectus sheath tunnelling, omentopexy, adhesiolysis, colopexy or epiploic appendicectomy and concomitant hernia repair to reduce risk factors and ensure maintenance over time. “These are all things you simply cannot do with other techniques,” Dor states. This notion of advanced laparoscopy as the go-to technique is also reflected in the most recent ISPD guideline update. However, Dor concedes, while an ideal-world
March 2022 – Issue 2
scenario may see this approach used more widely, the reality is that surgical theatre access poses a major logistical challenge, and a lack of proper surgical enthusiasm and training as well as the “big issue” of healthcare system costs also make laparoscopic techniques tricky to commit to. The flip side is that patient selection biases mean percutaneous alternatives tend to be less-affected by many of these factors—as they are cheaper, do not require theatre access, can be performed by nephrologists or specialised nurses, and allow the patient to leave hospital shortly after. “Quite a lot of people do have a percutaneous PD catheter insertion—and it works well for many patients, especially those deemed too high-risk to undergo general anaesthetic,” Dor continues. On the reasons why some prefer this approach, Dor says this is largely due to the aforementioned practicalities offered. “However, I would challenge that very fiercely,” he adds, “because I do not think we should settle for an option that is second-best and less safe—from a theoretical point of view, but also from a practical perspective.” Here, he cites bleeding complications, unsuccessful procedures due to inability to proceed safely, a lack of visibility (even under ultrasound), periprocedural pain/trauma for the patient, and ultimately a greater likelihood of interventions or failure, as being among the downsides to percutaneous catheter placement. “I do not think it is suitable for all patients, because there are clear contraindications, such as obesity and previous abdominal surgery, both in my view and in the ISPD guidelines,” Dor adds, also claiming that, in
surgeons. Swinnen then relayed details of the technique itself, claiming the entire procedure is done via a single 5mm incision. Accessing the peritoneal cavity is the “critical step” here, he added, and Jan Swinnen emphasised the importance of learning to insert the needle at the correct angle. The speaker drew comparisons between current acute PD protocols and his centre’s new Seldinger-based system—reporting a reduced timeframe from 8–12 weeks to two, and zero in-centre dialysis sessions or outpatient visits (versus 120 and four, respectively), with the latter. “The system we have introduced has been very successful and has taken over most of the PD work in our hospital,” he added. Expanding on this experience with USSPD, Swinnen said his centre embarked on a pilot project involving 10 basic cases in July 2019 and—as of December 2021—has completed 90 cases without seeing significant complications. “We are now placing up to six modified Seldinger PD catheters per week,” he reported. Swinnen noted other observations, including increasing acceptance and enthusiasm, ever-broadening use indications, and a shift away from haemodialysis towards PD nursing and early training. He concluded with a nod towards data from the first 65 of these cases, which were recently published in the Journal of Vascular Access, and found a technical success rate of 97% and saw some 36% of patients starting PD within 24 hours of catheterisation. The USSPD approach is also set to feature in a Kidney Academy CME module at www.kidneyacademy.com.
terms of equity of access, if a healthcare provider only offers percutaneous options, these contraindications may unrightfully preclude patients from receiving PD entirely—something he feels should “never happen”. He further notes that, even in patients not suitable for general anaesthetic, he personally prefers an open surgical approach with a regional block over percutaneous techniques, as the former is safer. “The problem in PD is that there are not many high-quality studies allowing us to compare these techniques in an unbiased way—which are all very much dependent on who is delivering them and the overall centre setup,” Dor claims. The importance of the technique used for catheter placement pales into insignificance, he believes, against the need for a multidisciplinary, dedicated team, with tailor-made approaches towards operation technique. Surgical and percutaneous approaches alike can be performed successfully and produce good outcomes in the hands of the right specialist and, if the patient has a contraindication for either, Dor says physicians should direct them towards the more suitable option. “But, if there is an equal choice…the patient should be advised on what the pros and cons are of each so they can declare their preferred technique,” he adds. “And this does not really happen— even in high-volume centres. We can improve on that, to put it mildly.” Dor also feels that the scope for new technologies to improve this state of play is limited right now, and, while the ability to conduct laparoscopic PD catheter insertions without requiring general anaesthesia would be “superb”, tangible developments do not seem to be on the horizon here. As such, he states that ensuring the presence of dedicated, enthusiastic, sufficiently trained professionals in the PD pathway is key moving forward. “I think the biggest innovation would be making PD accessible for everyone—and there should not be a single, surgical contraindication or technical reason why even the most complex, challenging patient cannot have a PD catheter placed,” Dor concludes. References: 1. Crabtree J H, Shrestha B M, Dor F J M F et al. Creating and Maintaining Optimal Peritoneal Dialysis Access in the Adult Patient: 2019 Update. Peritoneal Dialysis International. 2019; 39(5): 414–36.
Latest News
Clinical News VenoStent embarks on clinical trial to improve success rate of vascular surgery outcomes
VenoStent has announced successful enrolment in an initial feasibility clinical trial to test the safety and efficacy of its 3D-printed bioabsorbable wraps in humans—a new methodology to improve surgical outcomes for haemodialysis patients. Enrolment was completed in Asunción, Paraguay, involving 20 endstage kidney disease patients that were referred for creation of an arteriovenous fistula to enable haemodialysis treatments. The participants are being followed up for several months and VenoStent claims the study team has already seen highly encouraging safety and performance signals—which could indicate much greater clinical outcomes and quality of life for kidney disease patients treated with the VenoStent SelfWrap bioabsorbable perivascular wrap technology. By aiding the arterialisation process at the time of vascular surgery, the company’s proprietary scaffold is designed to solve the issue of reduced or blocked flow caused by neointimal hyperplasia within the blood vessels being used for haemodialysis access. Successful enrolment in this initial feasibility trial is set to support future regulatory submissions from VenoStent.
Xeltis initiates European first-in-human trial of restorative haemodialysis access graft
Xeltis has announced initiation of a clinical trial evaluating Axess, which it claims is the first ever restorative synthetic haemodialysis access graft. Several patients with kidney failure or advanced kidney disease requiring dialysis have already been successfully implanted so far as part of the European first-in-human trial. The Axess trial will evaluate the preliminary safety and performance of the graft in 15 end-stage kidney disease patients enrolled across five European sites. It is a prospective, single-arm, non-randomised feasibility study, and its primary endpoints are freedom from device-related serious adverse events after implantation and functional patency rate at six months. Axess grafts enable early puncturing, or initiation of dialysis, shortly after implanting—according to Xeltis. Over time, they turn into living blood vessels as their porous microstructure is colonised by the patient’s own tissue. “An off-the-shelf haemodialysis access solution capable of turning into a patient’s living vessel would combine the benefits of arteriovenous fistulas and grafts with none of their current, limiting compromises,” said one of the trial’s investigators, Matteo Tozzi (University of Insubria, Varese, Italy). “Patients with renal failure would be relieved of a significant clinical, physical and psychological burden if access to dialysis became straightforward and reliable.”
DaVita study indicates effectiveness of mRNA COVID-19 vaccines in dialysis patients
Dialysis patients who received mRNA COVID-19 vaccines had a lower risk of COVID-19 diagnosis post-vaccination and were less likely to be hospitalised or die following breakthrough infection compared to unvaccinated patients, as per a study led by DaVita Clinical Research and published in the Journal of the American Society of Nephrology. To assess COVID-19 vaccine effectiveness in this patient population, researchers evaluated electronic health records of 35,206 DaVita dialysis patients vaccinated with BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) between 1 January and 25 February 2021. These patients were matched to unvaccinated controlled groups and followed over time to observe future COVID-19 infections as well as related clinical outcomes. Researchers observed that the Pfizer/ BioNTech and Moderna vaccines were 78% and 73% effective in preventing COVID-19 infections, respectively. In addition, among vaccinated dialysis patients, the study found that SARSCoV-2 antibodies were detected in rates similar to those seen in the broader Phase III clinical trials of these two vaccines.
InnAVasc gains FDA nod for third study phase involving investigational haemodialysis graft
InnAVasc Medical has been granted US Food and Drug Administration (FDA) permission to commence the third phase of enrolment for its pivotal clinical study. “This is a big step forward to completion of the study,” an InnAVasc LinkedIn post states. The pivotal study in question is intended to assess the safety and effectiveness of the company’s investigational haemodialysis graft— the InnAVasc Graft (IG)—which is designed to be used immediately postimplantation. The IG is also intended to reduce needle-related injuries and complications and to be easier to locate under the skin, and—according to InnAVasc—it has the potential to facilitate more patients in the transition to home haemodialysis.
Natera validates kidney transplant rejection test in global Trifecta study
Natera has announced initial results from the global, multicentre, prospective Trifecta study, which assessed its Prospera with quantification test for kidney transplant rejection and was led by Phil Halloran (Alberta Transplant Applied Genomics Centre, Edmonton, Canada). “These new data from the Trifecta
study clearly demonstrate that Prospera with quantification can accurately predict rejection in kidney transplant recipients with indications for biopsy from a diverse population and is a useful tool for comprehensive evaluation of graft status,” said Halloran. The Trifecta study was designed to assess the performance of donorderived cell-free DNA (dd-cfDNA) and to evaluate the relationship between dd-cfDNA, donor-specific antibodies and molecular pathology. The initial analysis includes more than 300 sequential biopsy-matched samples, drawn between 2019 and 2021, with over 100 biopsy-confirmed rejections from more than 20 US and international sites. In the validation cohort, when differentiating rejection from nonrejection, Prospera with quantification delivered an area under the curve (AUC) of 0.81 and 0.89 using the 2019 BANFF criteria and molecular pathology, respectively, as the standards for rejection. The test also showed an AUC of 0.91 for differentiating rejection versus quiescence.
Amplifi vein dilation system demonstrates “encouraging” clinical results in first-inhuman study
Artio Medical has announced presentation of the full results from its first-in-human clinical study of the Amplifi vein dilation system by Surendra Shenoy (Washington University School of Medicine, St Louis, USA) at the 2021 VEITHSymposium (16–20 November; Orlando, USA). “Data from the first five patients treated with the Amplifi system demonstrated more than a doubling of forearm and upper arm cephalic vein diameters following a mean treatment period of 8.6 days,” said Shenoy. “We were able to successfully create an arteriovenous fistula [AVF] using treated veins in all patients and observed rapid and robust AVF maturation. These data are very encouraging, and I believe this technology has the potential to offer a much-needed solution for increasing AVF suitability and reducing maturation failure.” The Amplifi vein dilation system is designed to stimulate arm vein enlargement prior to AVF creation to make more patients requiring vascular access for haemodialysis eligible for AVF surgery, reduce the time required for AVF maturation, and increase successful maturation rates. “In this study, three of the five patients had pre-existing problems in the cephalic vein, which were made more apparent by Amplifi system treatment,” Shenoy added. “In one
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patient, an AVF was made more proximally and, in another, angioplasty was performed, and both patients went on to have successful AVF maturation and use.” Artio now intends to build on this initial clinical experience with a US investigational device exemption (IDE) trial, which is projected to begin enrolment in 2023.
Zynex announces first enrolment in haemodialysis clinical trial of fluid monitoring system
Zynex Monitoring Solutions has started enrolment in a haemodialysis clinical trial with its CM-1500 fluid monitoring system. The study, conducted at DaVita Clinical Research clinics, is aimed at further characterising changes in the device’s patented Relative Index during haemodialysis sessions. It is expected that the study will complete enrolment in the first quarter of 2022. Zynex obtained US Food and Drug Administration (FDA) clearance for the CM-1500—a non-invasive system intended to monitor patients’ fluid balance in hospitals and surgical centres—in February 2020. The company has said it expects to initially target operating rooms and surgeries that typically display substantial blood loss, as well as recovery rooms and intensive care units where internal bleedings are more common and difficult to detect until serious complications occur.
Symplicity Spyral
Medtronic launches SPYRAL AFFIRM study alongside new data on hypertension treatment preferences
Medtronic has initiated the SPYRAL AFFIRM investigational device exemption (IDE) study, which is set to evaluate the long-term safety, efficacy and durability of its Symplicity renal denervation (RDN) system in treating uncontrolled hypertension. The first patient was enrolled at Piedmont Heart Institute (Atlanta, USA). The trial will enrol 1,000 real-world patients with uncontrolled hypertension and associated comorbidities, such as isolated systolic hypertension, diabetes, and chronic kidney disease, across 100 global sites and will follow these patients for three years. Medtronic has also announced findings from a new study of patient preferences regarding the treatment of hypertension—which was presented at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November, Orlando, USA). The study saw 400 US patients surveyed on treatment mode, effectiveness and risk, and concluded that blood pressure reduction was the most important driver of patient preference over all other attributes like medication burden and treatment risks. Issue 2 – March 2022
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Latest News Biim
Industry News Fistula trials among key areas set to benefit from MedAlliance acquiring MDK Medical
Arteriovenous fistula (AVF) access is one of the key areas that is set to receive a boost following MedAlliance’s acquisition of its partner MDK Medical. MDK Medical has previously worked closely with MedAlliance to develop Japanese clinical studies for its novel sirolimus-eluting balloon, Selution SLR, in the treatment of peripheral arterial disease (PAD). This recent acquisition will, however, facilitate expansion of the Japanese clinical trial programme beyond PAD to areas including diseases of the inferior femoral artery, AVF access for dialysis in kidney disease patients, and a drugeluting balloon intended to treat erectile dysfunction. Selution SLR was awarded CE mark approval for the treatment of PAD in February 2020 and for the treatment of coronary arterial disease in May 2020. Meanwhile, the US Food and Drug Administration (FDA) has granted Selution SLR a total of four breakthrough designations concerning the treatment of atherosclerotic lesions in native coronary arteries, coronary instent restenosis, and peripheral belowthe-knee and AVF indications.
Outset Medical gains landmark CMS approval for Tablo home haemodialysis system
Outset Medical has announced that its Tablo haemodialysis system has received what it claims is the first ever approval from the Centers for Medicare & Medicaid Services (CMS) for a Transitional Add-on Payment Adjustment for New and Innovative Equipment and Supplies (TPNIES). This pioneering decision will help encourage healthcare providers to embrace new technology, enabling more patients to dialyse at home and reclaim their independence, according to the company. The TPNIES programme was introduced in 2020 by CMS to increase access to new and innovative medical technologies for end-stage kidney disease patients. As part of the recent TPNIES approval, healthcare providers will have access to supplemental reimbursement over the next two years to support their patients’ use of the Tablo system at home. Tablo Tablo is an intelligent, all-in-one device intended to solve the problems that have limited home dialysis adoption to date—including burdensome training requirements, complex machine operation and time-consuming preparation before treatments. Outset claims that is has also been designed to reduce the costs and complexity of dialysis, March 2022 – Issue 2
while simplifying patient and provider experiences.
Baxter launches My Kidney Journey portal to support kidney disease patients in Asia Pacific
Baxter Asia Pacific has announced the launch of My Kidney Journey—a comprehensive online portal intended to support patients living with chronic kidney disease (CKD) in the Asia Pacific (APAC) region. The portal has been developed to provide additional information on CKD, such as the symptoms, causes and stages, as well as balanced and up-to-date information on multiple treatment options to manage CKD like home haemodialysis, peritoneal dialysis, in-centre dialysis care and kidney transplantation. It also offers support to patients, families and caregivers by providing insights on ways to live well on dialysis, including coping with the emotional difficulties of a diagnosis and the demands of treatment. “Relevant sources of information, whether online or through support groups, will empower patients to navigate the complex kidney replacement landscape,” said Marjorie Foo (Singapore General Hospital, Singapore). “Access to information and support, alongside meaningful, shared decision-making consultations with their nephrology team, is key to supporting patients on their dialysis journey.” My Kidney Journey is now available to patients and the general public in 10 countries, and in nine different languages, across the APAC region, according to Baxter.
Fist Assist receives FDA Breakthrough Device designation for wearable vein dilation device
Fist Assist Devices has announced that it recently received Breakthrough Device designation from the US Food and Drug Administration (FDA) for its FA-1 device. The FA-1 device is a wearable, intermittent pneumatic compression device that is worn on the arm to enable presurgical vein dilation and, as such, promote arteriovenous fistula (AVF) creation. It compresses the outflow vein, which has both biological and physiological benefits, and—because it is automated—significantly improves patients’ compliance compared to other vein dilation alternatives, according to Fist Assist. The device is intended for use in adult patients diagnosed with chronic renal failure whose preoperative assessment of the venous anatomy suggests that superficial arm vein or perforator vein size is inadequate for the creation of an AVF for haemodialysis access. Access to the FA-1 device for US patients with an end-stage kidney disease vein dilation indication is now set to be expedited through the FDA Breakthrough Device programme.
Fresenius and Biim to expand usage of portable ultrasound system for predialysis needle cannulation
Fresenius Kidney Care and Biim Ultrasound have announced an agreement to expand usage of the latter’s innovative ultrasound system for assisting needle cannulation prior to dialysis treatment. Fresenius claims to have successfully piloted the use of Biim’s ultrasound system at more than two dozen dialysis centres in 2020—in an effort to improve patient experiences and reduce access failures—and this fresh, expanded rollout will involve hundreds of additional centres throughout the USA in early 2022. While often used in a hospital setting, ultrasound has not yet been widely or routinely used in outpatient dialysis centres to assist with cannulation, according to Fresenius. Biim is a fast, flexible, cordless ultrasound system that has the ability to scan patients and review images in seconds, offering a practical way to enhance decision-making and help improve patient outcomes. It is also designed to be easy to operate, with a simple app interface, so that scanning can begin within seconds.
OrganOx completes £6.4 million equity fundraise to boost utilisation of donated kidneys
OrganOx, the producer of the Metra normothermic machine perfusion (NMP) product, has announced the completion of a £6.4 million equity fundraise. The fundraise was led by Oxford Investment Consultants and supported by both existing and new shareholders, and enabled £5.35 million in convertible loans from August 2020 to be converted into equity for OrganOx. This investment will allow the company to accelerate a number of programmes in its research and development pipeline, and supported a Phase I clinical trial for a normothermic kidney perfusion device in late 2021. As with liver transplantation, there is a clear unmet clinical need for technologies to improve the utilisation of donated kidneys, reduce waiting list mortality, and ensure more patients can benefit from a life-changing transplant, OrganOx states.
Arrow recalls percutaneous thrombolytic device kits over risk of separation
Arrow International has recalled its Arrow-Trerotola over-the-wire 7Fr percutaneous thrombolytic device (PTD) kits, which are used to remove clots in adult patients who have arteriovenous fistulas and synthetic dialysis grafts. The recall has been attributed to the risk of the orange inner lumen of the Arrow-Trerotola catheter’s tip component separating from the device’s self-expanding basket. A statement from the US Food and Drug Administration (FDA) adds that, if this
occurs, the lumen may fracture and detach, and block the blood vessel(s) it is being used in. Resulting health consequences depend upon where the fractured tip component embolises, the FDA statement continues. If the embolisation is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy. In some cases, the embolisation could be central, or possibly even to the heart or pulmonary arteries, potentially leading to serious adverse events, such as vessel damage or death, the statement adds. The FDA has identified this as a Class I recall—the most serious type of recall—meaning use of these devices may cause serious injuries or death. To date, there have been seven complaints and no injuries or deaths reported for the Arrow-Trerotola PTD kits. Arrow, which is a subsidiary of Teleflex, has recalled 3,241 of these devices in the USA following initiation of the recall in August 2021.
New company to bring high-realism simulation for interventional procedures closer to clinicians
Anais Medical, a new company founded by Parc Taulí Research and Innovation Institute (I3PT)—and led by José Ibeas (Parc Taulí University Hospital, Barcelona, Spain)—intends to develop practical educational material that uses realistic models and simulations to improve the training and skills of clinical experts in interventionist procedures, especially in relation to José Ibeas dialysis patients. “While physical models allow practical training and familiarisation with invasive procedures in a risk-free environment, virtual reality offers the first interaction with anatomy in an environment that allows immersion in XNUMX dimensions,” Ibeas said. The company has been established to enable the design and manufacture of highly realistic simulation models so that medical students, residents and nurses can practice and develop necessary skills before performing their first invasive procedures on patients. These may range from placing catheters in the jugular vein or creating a fistula to endovascular surgeries like angioplasties or stent placements.
Medicare launches new Kidney Care Choices models in USA
The Centers for Medicare and Medicaid Services (CMS) has launched its new Kidney Care Choices (KCC) models in the USA. This new structure intends to provide financial incentives for healthcare providers to coordinate care for Medicare beneficiaries with late-stage chronic kidney disease and end-stage kidney disease, and to delay the onset of dialysis while incentivising kidney transplantation. The KCC models were first announced in 2019, and formally began on 1 January 2022. Fresenius Medical Care North America, DaVita Integrated Kidney Care, Strive Health and Global Nephrology Solutions are among leading companies to have announced participation so far this year.
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Events
18–19 March
12 May
6–10 April
19–22 May
International Renal Conference Bruges, Belgium www.renalconference2022.com
7th Israeli Vascular Access Conference Tel Aviv, Israel www.vascularaccesssociety.com/activities
National Kidney Foundation (NKF) Spring Clinical Meetings Boston, USA www.kidney.org/spring-clinical 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.
26–28 April
Charing Cross (CX) Symposium London, UK, in-person and virtual www.cxsymposium.com/cx2022
6–9 June
Leipzig Interventional Course (LINC) Leipzig, Germany www.leipzig-interventional-course.com/ visitors/linc-2022
7–9 June
59th European Renal Association (ERA) Congress Paris, France www.era-online.org/en/paris2022
UK Kidney Week (UKKW) Birmingham, UK www.ukkw.org
4–8 June
9–11 June
American Transplant Congress (ATC) Boston, USA www.atcmeeting.org
Vascular Access for Hemodialysis Symposium Charleston, USA www.vasamd.org/events/upcoming-events
Meet our editorial board Nicholas Inston
Ziv Haskal
Stephen Hohmann
Robert Jones
Chairman of Executive and Editorial Board
Board Member
Board Member
Board Member
Nicholas Inston is a transplant and vascular access surgeon, and the clinical service lead for renal surgery, at Queen Elizabeth Hospital in Birmingham, UK.
Ziv Haskal is a professor of radiology, and an interventional radiologist and interventional oncologist, at the University of Virginia School of Medicine in Charlottesville, USA.
Stephen Hohmann is a vascular and general surgeon at the Texas Vascular Associates clinic in Dallas, USA.
Robert Jones is an interventional radiologist at Queen Elizabeth Hospital in Birmingham, UK.
Issue 2 – March 2022