New study examining UK Biobank data associates retinal age gap with ESKD

Patients likely to develop end-stage kidney disease (ESKD) may first exhibit ageing in the eye, a study in the American Journal of Kidney Disease (AJKD) has suggested. Retinal age gap, a measure which comprises retina-predicted age minus the patient’s actual age, was “significantly associated with incident ESKD,” said the study authors, led by Zhuoting Zhu (University of Melbourne, Melbourne, Australia).

THEY NOTED THAT PATIENTS WITH THE SAME chronological age could exhibit different biological ages, highlighting the “growing evidence showing the relationship between ageing biomarkers” and chronic kidney disease (CKD) and ESKD. Discovering markers that may indicate the onset of ESKD early may allow clinicians to make earlier interventions to prevent progression of the condition. The study authors stipulated that existing studies on the utility of biomarkers were sometimes limited by “cross-sectional designs and small sample sizes.” Their study sought to change that for the health of the retina, which “has long been considered as a window to the kidney,” and to explore whether the retinal age gap could predict for ESKD.

The study utilised the data of the UK Biobank, which includes those of over 500,000 patients aged 40–69. Employing a deep learning model, they used fundus images of the eyes of 46,969 patients to predict their retinal age gap. Those patients’ ESKD status and diagnosis date were obtained from National Health Service (NHS) Digital. The follow-up period was from the date of fundus image acquisition to “the first occurrence of ESKD or lost to follow-up or death, whichever came the earliest.”

The results showed a statistically significant association between retinal age gap and ESKD occurrence. For each one-year increase in the retinal age gap, patients were 9% more likely to experience incident ESKD. There was also a notable difference in retinal age gap’s association with ESKD between male and female patients, with an 8 and 13% risk increase respectively with each one-year increase. A “trend of increasing association was noted with incident ESKD across different quartiles of retinal age gaps,” and those in the fourth quartile were at a significantly greater risk of ESKD compared to those

NEXTKIDNEY, A NETHERLANDS-BASED company that has developed the world’s first fully-portable haemodialysis device in the form of the NeoKidney, has raised €4.1 million in a new crowdfunding effort.

Carried out on the Oneplanetnow Dutch fundraising platform, and co-led by the Generous Minds initiative, the funding is a major step in the development of the device. Planned to utilise only four litres of fluid per dialysis session, the device promises chronic kidney disease (CKD) patients “more freedom and a significant improvement in quality of life”.

The portable dialysis project “stems from the initiative of the Dutch Kidney Foundation and health insurers CZ, ZilverenKruis and Menzis”. The company describe the device as being in “the final stages of development”, with a working prototype already complete. Safety testing went underway in Singapore in April 2022, while clinical trials will take place in 2023 in both France and The Netherlands.

“We are investing in the portable artificial kidney and its introduction into healthcare because we believe that the portable artificial kidney dramatically improves the lives of kidney patients,” Joep de Groot, CEO of CZ, said. “The portable artificial kidney also contributes to a reduction in healthcare costs, partly because it requires less deployment of scarce medical staff. Thereby, this unique dialysis machine helps to keep healthcare in The Netherlands widely acces- in the first (p=0.002).

The study authors made the case in their discussion that retinal age gap is thus “a promising biomarker of future occurrence of ESKD independent of traditional risk factors.” They cited a Mendelian randomisation study into the link between ageing and kidney disease led by Sehoon Park (Seoul National University, Seoul, South Korea), stating that “telomere attrition was significantly associated with a higher risk of kidney function decline,” but made the case for retinal age gap as a biomarker, not least due to “its non-invasive nature, ease of calculation and accuracy.” Finally, they speculated about the mechanisms explaining the association, citing the retina and kidneys’ “common developmental pathway.” These included inflammation, endothelial dysfunction and oxidative stress. While previous studies, they said, have found retinal age gap an effective biomarker for “vascular stiffness and vascular ageing,” their study may pave the way for it to play a larger role—and increase the compliance rate—in kidney disease screening.

IceCure releases preliminary data on ProSense cryoablation system

IceCure Medical, developer of the minimally-invasive ProSense System for cryoablation, which destroys tumours by freezing, has announced interim results from the ICESECRET study for the treatment of patients with small renal masses (SRM) who cannot be offered kidney-preserving surgery. Data were presented at the Urological Association Conference (14 December, Eilat, Israel). The presentation, titled “Renal Mass Cryoablation - Interim Analysis ICESECRET Study”, was delivered by Nasir Said (Bnai Zion Medical Center, Haifa, Israel).

According to the presentation, out of the 115 patients enrolled, 107 patients (112 lesions) returned for follow-up with a mean duration of 22.8 months and a range 12-60 months. In a subgroup of patients with no previous history of kidney cancer on the same kidney and a lesion ≤3cm, an 89.5% recurrencefree rate was observed at a mean follow-up time of 22.2 months when the procedure protocol was followed.

The recurrence-free rate was 85.1% for the 107 patients (91 patients, including 13 patients who underwent a second cryoablation), at a mean followup period of 16.5 months. Five serious adverse events were reported, four of which were of mild severity and were treated conservatively and resolved within one to five days, with one severe complication of a new onset of ipsilateral hydronephrosis seven months after the cryoablation procedure that led to nephrectomy.

Cryoablation time and hospitalisation time were relatively short, up to approximately 25 minutes and two days, respectively. The presentation concluded that, based on these interim results, cryoablation is safe and effective for treating renal masses under five centimetres.

Medtronic announces first patient enrolled in Expand URO trial for Hugo roboticassisted surgery

Medtronic has announced the first patient enrolled in the Expand URO US clinical trial for the Hugo roboticassisted surgery (RAS) system. The robotic-assisted prostatectomy procedure was performed by Michael R Abern (Duke University Hospital, Durham, USA) at Duke University Hospital in North Carolina, USA.

Minimally invasive surgery, including robotic-assisted surgery, offers fewer complications, shorter hospital stays, faster return to normal activities, and smaller scars. Urologic procedures are one of the most commonly performed with the assistance of a surgical robot. The Hugo RAS system is intended to be used in this study for urologic surgical procedures including radical prostatectomy, radical cystectomy, and nephrectomy (partial or radical) procedures at sites in the USA.

The Expand URO clinical trial is being conducted pursuant to an Investigational Device Exemption from the US Food and Drug Administration (FDA). Up to 122 patients will be enrolled in the study at six sites in the US. The Hugo RAS system, combined with Touch Surgery Enterprise, purports to offer a “smart, digitally enabled surgical experience”. Outside the US, it is in use at hospitals across three continents in a range of procedures within urology, gynaecology, and general surgery.

A Medtronic press release detailed that the system is commercially available in certain geographies. Regulatory requirements and status in individual countries and regions will determine market availability of the Hugo RAS system and approved indications. In the USA, the Hugo RAS system is an investigational device not for sale.

Nephroflow as good as Transonic for measuring VA flow, finds JVA study

NephroFlow device is as effective for ultrasound dilution (UD) for vascular access (VA) as existing devices such as the Transonic VA flow measurement technology, according to a Spanish study comparing the two led by Jose L Merino (Hospital University del Henares, Madrid, Spain) and published in the Journal of Vascular Access (JVA). NephroFlow meets the standard set by Transonic and demanded by current Spanish guidelines for UD-based assessment of the complication risks associated with arteriovenous fistula (AVF) for haemodialysis (HD).

The study was conducted with 44 patients with a mean age of 67 ± 12 years who had been on VA for at least three consecutive months. Patients were studied on the second day of their HD if they received three or more sessions, or the first day of the week if they received two.

It was found that the mean flow for Transonic was 1222±805 ml/min while for NephroFlow it was 1252±975 ml/ min. The authors described this as a representing a result “comparable to the accepted gold standard method” for VA flow surveillance. They claim that, upon review of other studies, “there is no method with better evidence than classic UD methods for VA surveillance.” Other methods such as duplex ultrasonography (DUS), they argue, take longer to achieve a measurement, as suggested for DUS in the study of Karava et al. The “speed for measurement could be a favourable aspect of the NephroFlow method,” they added.

With all this considered, the authors maintained that “as far as we know, this is the first study comparing both methods [of UD assessment of VA].” They concluded by suggesting that the NephroFlow device “could be applied in the surveillance of VA in the detection of VA at risk, as recommended by the [Spanish] guidelines.”

Speaking exclusively to Renal Interventions, Merino supplemented this conclusion by saying that “we continue to use the device in our daily routine and its speed allows us to optimise nursing times. Although several guidelines question the benefit of routine surveillance, the Spanish Multidisciplinary Group on Vascular Access (GEMAV) guidelines and we believe low-cost and easily applicable devices can improve vascular access survival.”

“Impressive” 12-month Flex vessel prep data presented at VEITHsymposium

VentureMed Group, a privately held medical device innovator in access management for arteriovenous (AV) fistulas and grafts and vessel preparation for interventional treatment of peripheral arterial disease (PAD), recently presented new data at the VEITHsymposium, (15–19 November, New York, USA). Overall, the data presented demonstrated that Flex vessel prep used prior to balloon angioplasty improves 12-month outcomes both in PAD and AV fistulas and grafts.

“AV Access management is a critical component of successfully treating AV patients over time,” said John Aruny (Dialysis Access Institute, Orangeburg, USA), primary investigator of the Flex Vessel Prep AV registry clinical study, the 12-month outcomes of which he presented at VEITH. “The FLEX AV Registry 12-month outcomes

Management programmes. The majority of patients were being treated by their primary care physician.

The study was conducted in collaboration with the Mount Sinai Health System’s Population Health Ambulatory Pharmacy and Condition Management programmes and included 1,686 patients seen by 75 providers at 20 clinical sites. The real-world evidence study demonstrated that patients with early-stage DKD and a high risk KidneyIntelX score received higher frequency of clinical management visits, introduction to guideline-recommended medications, and specialist referral for disease management compared to those who were identified as low- or intermediate-risk patients.

When evaluating new or modified prescriptions for hypertension at six months, both angiotension-convertingenzyme inhibitors and angiotensin receptor blockers achieved a greater than 20% change in patients with hypertension in the high risk group vs. the low risk group. Medication management for use of SGLT2 inhibitors was even more pronounced; 25% of patients in the high risk group received new SGLT2 inhibitor prescriptions vs. 7% in the low risk group, a 4.5fold increase. Thus, KidneyIntelX enabled physicians to take guidelinerecommended clinical actions in high risk, early stage (stage 1-3b) diabetic kidney disease patients. New referrals by risk group were 6% for low risk, 12% intermediate risk and 15% high risk.

Thulium fibre laser found to be clinically comparable to ‘gold-standard’ kidney stone treatment

shows that utilising Flex vessel prep provides more time between interventions and continues to excel in the very difficult cephalic arch lesions.”

The study was a single-arm, prospective study conducted in eight centres in the USA with 114 real world patients. The Flex AV Registry 12-month outcomes demonstrate sustained patency across most patients and particularly good results specifically in the cephalic arch, with no observed serious adverse events.

Renalytix share new data suggesting their KidneyIntelX bioprognostic test improves decision-making

Renalytix has announced the publication of new real-world evidence in Primary Care and Community Health demonstrating the company’s KidneyIntelX bioprognostic test resulted in changed clinical decision-making for patients in the early-stage of diabetic kidney disease (DKD) being cared for within the Mount Sinai Health System’s Population Health Ambulatory Pharmacy and Condition

The recently introduced thulium fibre laser (TFL) does not improve the clinical outcomes of laser treatment for urinary stones compared to the standard for laser stone therapy, reports a randomised trial in the Journal of Urology, an official journal of the American Urological Association (AUA).

Despite its theoretical technical advances, the new study shows TFL has no significant clinical advantage over a modern high-power pulsemodulated holmium-yttrium aluminium garnet (Ho:YAG) laser in ureteroscopic lithotripsy of stones. “Our findings suggest that either of these currently available laser systems can provide excellent clinical outcomes treating non-staghorn renal and ureteral calculi in skilled hands,” comments lead author Christopher R Haas (University of Wisconsin, Madison, USA).

Approved by the US Food and Drug Administration (FDA) in 2019, the TFL is a relatively new alternative to Ho:YAG energy for laser lithotripsy of urinary stones. The Ho:YAG laser has been the “gold standard” of care for laser lithotripsy since the 1990s.

In this minimally invasive procedure, laser energy is delivered through a fibre passed through a ureteroscope directly to the visualised stone to break up or “dust” stones into pieces small enough to pass down the ureter.

The results showed that the two lasers required similar time to break up stones into passable fragments of 1mm or less: an average of 19.9 minutes with the TFL and 21.4 minutes with the Ho:YAG laser. Haas et al concluded that the trial “suggests no significiant clinical advantage” for either technology.

Genetically-modified pig patent promises expansion of kidney xenotransplantation

Makana Therapeutics, a global leader in the field of xenotransplantation, was granted an important European patent that will catalyse xenotransplantation efforts abroad, the company has announced. Makana is working to solve the organ shortage crisis by making genetically modified pigs for use as organ donors for human recipients. The patent was granted on the TKO pig, or “Triple Knockout,” which is a combination of three xenoantigen gene knockouts in the pig that effectively camouflage the cross-species grafts from the human recipient’s immune system.

Makana has demonstrated compelling results in xenotransplantation. “Our knockout pigs combined with our advancements in immunosuppression and patient matching have resulted in the longest and most consistent preclinical survival data in the xenotransplantation field,” said Mark Platt, the company’s president and chief executive officer.

The Triple Knockout Pig was discovered in the lab of Joe Tector (University of Miami Medical School, Miami, USA), who is also the founder of Makana. “The Triple Knockout Pig has fundamentally changed the xenotransplantation field,” Platt said. “The organs from this animal have been shown to be an acceptable match to more than 30% of patients waiting for a kidney transplant, and likely more than 70% of patients can benefit from these organs with available pretransplant treatment.”

Makana is in talks with the US Food and Drug Administration (FDA) regarding next steps to conduct the first-ever human clinical trial in kidney transplant. This recent development will add to Makana’s portfolio of intellectual property, which they say “will help the company to serve patients in Europe who are in desperate need of a transplant”.

Lydus Medical announces US FDA clearance of microvascular anastomosis aid device

Lydus Medical has announced that its Vesseal device has received US Food and Drug Administration (FDA) 510(k) clearance. The Vesseal is a microvascular anastomosis suture deployment system, for standardised omnivessel anastomoses, enabling “simple, fast, safe, and effective procedures”.

Until now, microvascular anastomoses have been performed manually. Manual microanastomoses are time- and labour-intensive, require a long learning curve, a unique skill set and great surgical dexterity. The Vesseal is designed to mimic the skill set and dexterity needed to deliver quality patient care in microsurgical anastomoses. It is described as offering “simple, accurate, dependable and consistent results” through symmetrical placement of eight microsutures at the anastomosis site.

“FDA clearance of the Vesseal is a significant milestone both for innovation in microvascular anastomoses, and for Lydus Medical. It is common knowledge that there are large clinical unmet needs around microvascular anastomosis,” said Jessica Weiss, CEO of Lydus Medical. “Clinicians who used the Vesseal stated that it shows a significant advantage over the manual anastomosis and provides more consistency in the procedure. We believe that the Vesseal will support enhanced outcomes in microsurgical procedures, as well as improved patient care”.

Baxter restructures renal unit into independent company amid new strategy to increase innovation liberDi CEO, Hezkiah Tsoory remarked, that “receiving FDA clearance for our state of the art digital dialysis clinic technology, is a huge achievement for liberDi. liberDi’s system is designed to provide these patients with ease of use, freedom of movement, automatic catheter connection flush technology and patient monitoring, while performing their daily dialysis activities from the comfort of their home or workplace”. liberDi conducted two initial clinical studies to demonstrate the safety and effectiveness of the portable peritoneal dialysis system on patients requiring dialysis. For this, 42 subjects used the system for dialysis under the supervision of three medical centres in Israel. liberDi also performed a human factor validation study evaluating all user groups: people requiring dialysis and their caregivers, as well as healthcare professionals such as nephrologists and dialysis nurses. The study simulated a real-world environment and were said to prove that anyone can operate the system following a single 90-minute proper training session.

Baxter International has announced a new strategic roadmap designed to accelerate innovation and improve its “operational effectiveness” and long-term performance. These changes include a plan to spin off the company’s Renal Care and Acute Therapies global business units into an independent, publicly traded company; a simplified commercial and manufacturing footprint to enhance underlying business performance; and further portfolio actions to improve Baxter’s capital structure, including a review of strategic alternatives for the BioPharma Solutions business.

The new kidney care company will benefit from its existing product portfolio and “robust service capabilities that support its therapies delivered in the home, clinics, and intensive care unit (ICU)”. As a standalone entity with its own investment priorities and enhanced management focus, the new kidney care company is intended to be better positioned to pursue growth opportunities and invest in innovation.

Over the past several years, Baxter has executed many initiatives to strengthen its ability to deliver on its vision to transform healthcare. To better achieve these goals, the company is working to finalise a new operating model that it will begin to implement in parallel with its planning for the proposed spinoff of the Renal Care and Acute Therapies businesses.

Digital dialysis device from liberDi receives FDA approval liberDi has announced that it has received regulatory clearance from the US Food and Drug Administration (FDA) for its digital dialysis clinic, which allows patients to perform dialysis at home or at the workplace, by themselves, monitored by their physician using the advanced telemedicine capabilities of the system.

XORTX submits patent application for methods for early detection of kidney disease

XORTX Therapeutics, a late-stage clinical pharmaceutical company focused on developing innovative requiring renal replacement therapy. Two genes are associated with ADPKD, PKD1 and PKD2, with mutation of PKD1 having a higher prevalence (85% of cases), an accelerated progression and more severe renal disease. Mutations are inherited in an autosomal dominant manner and display a vast spectrum of clinical disease severity depending on the inherited mutation and other factors, including age and sex.

EU Commission to propose delay to MDR implementation

Europe’s health commissioner, Stella Kyriakides, has announced that proposals to extend the transition period for the implementation of the European Union’s (EU) Medical Device Regulation (MDR) will be put forward in early 2023.

Kyriakides informed health ministers from the EU’s 27 Member States of the plan at a meeting of the Employment, Social Policy, Health and Consumer Affairs Council in Brussels on Friday (9 December), where the council members discussed the current status of the implementation of the MDR.

The regulation—which changes the way that medical devices are certified for use in the European market—first came into effect in 2021 with an initial three-year transition period, having been delayed by one year in 2020 due to the onset of the COVID-19 pandemic.

Concerns have been raised over the impact of the transition to the new regulatory regime, with the European Society of Cardiology (ESC) previously calling upon ministers to act to prevent a “shortfall of essential medical devices for cardiovascular patients”, which the Society warned could include diagnostic and ablation catheters and some stents.

“Patients rightly expect to have safe and high-quality medical devices,” Kyriakides told journalists at a press conference that followed the council meeting, where she acknowledged it is now a “crucial time” for the transition to the new rules. She described the policy shift as a response to global supply shortages of medical devices.

FDA grants Breakthrough Device Designation for RenalGuard AKI prevention technology

therapies to treat progressive kidney disease, has submitted a Patent Cooperation Treaty (PCT) patent application seeking international patent protection for the patent entitled “Compositions and Methods for Diagnosis, Treatment and Prevention of Kidney Disease”.

Recent discoveries at XORTX and by its independent research laboratories, suggests that certain individuals, most at risk for accelerated kidney disease progression, may be identified, diagnosed, and treated based upon a novel risk profile. This new patent application proposes proprietary diagnostic methods, and potential therapeutic approaches for personalising the medicines used to treat those most at risk of health consequences of aberrant purine metabolism in cystic kidney diseases.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically linked nephropathy and the fourth most common cause of kidney failure

CardioRenal Systems have announced that the US Food and Drug Administration (FDA) has granted Breakthrough Device Designation for its RenalGuard Therapy device for the prevention of Acute Kidney Injury (AKI) in patients at risk for Cardiac Surgery Associated AKI (CSA-AKI).

“The high prevalence of acute kidney injury in cardiac surgery today is a well-known risk. We look forward to building further clinical validation that RenalGuard Therapy can provide the solution to reduce the prevalence of CSA-AKI,” said Ilya Budik, CEO of CardioRenal Systems.

The FDA’s Breakthrough Device Designation is a federally legislated programme is designed to expedite the review process and to facilitate the clinical trial development of devices that treat life-threatening conditions or irreversibly debilitating human disease or conditions. Budik commented that “we are looking forward to the initiation of the upcoming US pivotal study”.

Conference Calendar

17–19 February

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

01–03 March

British Transplantation Society (BTS)NHS Blood and Transplant (NHSBT) Joint Congress Edinburgh, UK bts.org.uk/events-meetings/bts-nhsbt-jointcongress-2023

04–09 March

Society of Interventional Radiology (SIR) 48th Annual Scientific Meeting Phoenix, USA www.sirmeeting.org

Meet our editorial board

Nicholas Inston

Chairman of the Editorial Board

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

30 March–02 April

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

11–15 April

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

25–28 April

Charing Cross (CX) Symposium 2023 London, UK cxsymposium.com

26–29 April

13th International Congress of the Vascular Access Society (VAS) Porto, Portugal vas2023.com

07–10 May

American Nephrology Nurses Association (ANNA) National Symposium Palm Springs, USA annanurse.org/events/2023-national-symposium

19–21 May

Vascular Access Society of the America (VASA) Hands-On Practicum on Hemodialysis Access Houston, USA vasamd.org/events/2023-practicum

Ziv Haskal Board Member

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

Stephen Hohmann

Board Member

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

Robert Jones

Board Member

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