Koen van der Bogt is a vascular surgeon at Haaglanden Medical Centre (The Hague, The Netherlands) and Leiden University Medical Centre (Leiden, The Netherlands). Joris Rotmans is professor of internal medicine at Leiden University Medical Centre (Leiden, The Netherlands). They write on the promise of dynamic arteriovenous fistulas as a solution to complications caused by high flow-rates.
Ever since Leiden University’s graduate Willem Kolff created the first dialysis machine in 1943, the vascular access community has been struggling to provide adequate vascular access solutions that enable a durable flow that is high enough for running dialysis sessions of about 350ml/min.
Since the 1960s, we routinely create arteriovenous fistulas (AVFs) that run a constant supraphysiological blood flow of typically 1000ml/min or higher. Due to high flow, vascular access patients experience diminished hand perfusion, suffer from the effects of compensatory intimal hyperplasia, stenosis, and angioplasties, may experience aneurysmal degeneration, spend significant time on dialysis wards for compression of needling sites, and undergo negative cardiac remodelling due to constantly elevated cardiac output. Vascular access complications—mainly stenosis and thrombosis—require approximately 1.5 interventions per patient per year to maintain functional vascular access. The corresponding healthcare costs relating to these interventions range between US$8,000–32,000 per patient per year. In the USA alone, total costs related to vascular access management surmount US$3 billion per year. Until now, no comprehensive solutions have been available to diminish these side-effects while protecting the vascular access and, above all, the patient.
Some nine years after Kolff’s discovery, the southern part of the Netherlands suffered a major flooding, leading to almost 2,000 casualties and 72,000 people seeking evacuation. It was due to a perfect storm; there was a king tide in combination with a strong north-western storm, driving up the water against the dikes and ultimately leading them to break through. The entire south-western part of the Netherlands was flooded. From then, Delft University graduate Johan van Veen, an engineer working at the state department of infrastructure and water management, lead the creation of the Delta Works flood protection system. This system of dynamic dykes only closes in case of danger, while normal water flow, including movements of animal species, is left unaffected under normal circumstances.
Humbly building further on this Dutch heritage, our group—with experts from Leiden and Delft from the fields of vascular surgery, nephrology, and biomedical engineering—has set out to bundle our forces to improve the quality of life of vascular access patients. This aim is the driver for the creation of the dynamic AVF, essentially providing vascular access only when the patient needs it. The prototype of the dynamic AVF consists of several patented parts: A dynamic valve, a cable, and an actuator. A narrow piece of expanded polytetrafluoroethylene (ePTFE) graft is anastomosed between an artery and a target vein, essentially creating a side-to-side anastomosed AVF. The valve mechanism can then be placed over the piece of graft, while the cable runs to a distant subcutaneous plane where the actuator is implanted. The actuator, and thereby the valve, may be activated non-invasively by an external magnet that can be placed on the skin.
With this non-invasive steerable device, blood flow can be optimised before dialysis, while a return to physiological venous flow can be established towards the end of the dialysis. The width of the ePTFE graft is chosen so that it is wide enough to provide enough force to fully close and open while being narrow enough to prevent a dead space when closed. By doing so, the risk of thrombosis will likely not be increased as compared to current vascular access solutions—around 35% in grafts and 11% in autologous AVFs.
The return to physiological flow, as enabled by the dynamic AVF, may offer a significant decrease in turbulence for over 150 hours per week, as compared to current AVFs and arteriovenous grafts (AVGs). This high turbulent flow is a main driver for intimal hyperplasia, stenosis, and thrombosis, as well as the consequent bulk of interventions to treat this. Therefore, a normalisation of flow outside the dialysis sessions should significantly decrease the number of (often painful) reinterventions to treat stenosis and thrombosis. Moreover, this will lead to a considerable decrease in societal costs.
Currently, 5% of patients experience complaints of distal ischaemia because of the preferential flow to the AVF or AVG. This number may normalise with the dynamic AVF as in between dialysis sessions, arterial flow will run towards the hand, without interference from the AVF.
Beyond immediate benefits, a normalisation of blood flow during most of the non-dialysis time will offer a period of rest for the heart. A staggering one third of end stage kidney failure patients suffer from heart failure. It has already been shown that a fistula leads to left ventricular hypertrophy, and that the abandonment of an AVF leads to a decrease in left ventricular mass. Therefore, the dynamic AVF may offer cardiac protection by diminishing the cardiac burden of continuous high flow, hopefully minimising the already high cardiac morbidity and mortality in dialysis patients.
Most importantly, there is much to gain for the patient. A realistic fear of debilitating or even life-threatening bleeding complications, especially in aneurysmal AVFs (some 20%), is a significant burden for the patient. This fear may be socially invalidating. Moreover, the prevention of bleeding from needling sites requires additional time in the hospital, presenting another social impairment. These factors together hamper home dialysis in many cases. The dynamic AVFs ability to titrate blood flow could address these concerns, making home dialysis a more viable option for many patients.
In its preclinical phase, the dynamic AVF presents a ground-breaking solution to vascular access-related complications. Animal studies are underway, paving the way for a true vascular access-on-demand system that could transform the landscape of dialysis care. To enable timely clinical translation, we have initiated a spinoff company by the name of XS Innovations. XS Innovations has recently won the Dutch Research Council’s Venture Challenge, strengthening our continuous push for a better quality of life for dialysis patients.
Disclosures: Joris Rotmans is co-founder of XS Innovations, president of the Vascular Access Society and a consultant for Xeltis, Koen van der Bogt is co-founder of XS Innovations.
