In patients suffering from end-stage kidney disease the kidneys can no longer adequately filter the body’s blood of excess water and waste products. This life-threatening condition is diagnosed in thousands of patients each year in The Netherlands alone, with millions affected globally. Due to a scarcity of suitable donor kidneys, and the difficulties in transplanting them, most of these patients rely on haemodialysis as kidney replacement therapy. In this treatment, blood is taken from the body, passed through an external filter, and then returned. Usually this is performed during 3 sessions of 4 hours per week.
A critical component in haemodialysis is the vascular access (VA), which is necessary to allow sufficient blood to be taken from the body easily and frequently. This is also known as the patients’ lifeline. Most often, blood is taken from the arm due to the superficiality of the vessels. However, the typical flow rates in these vessels of ~50mL/min are far too low to supply the dialysis machine of the ~350mL/min it requires for efficient filtering. This challenge is usually overcome by surgically placing an arteriovenous fistula (AVF) in the arm: a vein is cut open and sutured to a hole in the side of an artery. This essentially creates a short circuit in the blood circulation which drastically increases blood flow to enables dialysis. In some cases a synthetic tube is used to create this connection known as an arteriovenous graft (AVG). Directly after placement, the vein starts to adapt to the altered flow conditions and to accommodate a sufficiently high flow for dialysis several weeks later, in a process known as maturation.
Unfortunately the vascular access fails to mature in many patients, and when it does mature, maintaining patency highly uncertain. Patients thus require frequent interventions to restore functionality of their vascular access in order to continue their treatment. In contrast, complications such as aneurysms and high-output heart failure occur when the VA does remain functional. As such, some patients receive their haemodialysis treatment through central venous catheters (CVCs) to bypass the need for a high-flow arteriovenous connection. However, this modality relies on a permanent transcutaneous tube that is placed directly into a central vein. Although immediately usable, these have their own disadvantages such as thrombosis and infection risks. The inherent drawbacks to all vascular access types highlight the critical need for novel strategies to optimise VA. Due to the mechanical and fluid dynamic nature of vascular access, innovation through medical devices holds significant promise for improving patient outcomes. This dissertation aims to develop and evaluate a novel medical device for improved vascular access for haemodialysis. Chapter 2 introduces a structured development framework tailored to the European regulatory environment. The Medical Device Regulation (MDR) imposes stringent requirements for high-risk devices, particularly around safety and clinical evidence.
A question-based development strategy is proposed to help guide decision-making, identify knowledge gaps, and improve communication across stakeholders throughout the device life cycle.
Chapter 3 addresses the off-label use of CVCs for power injection of contrast media during imaging procedures. An in vitro study demonstrated that pressures during such injections remained below burst thresholds, suggesting incidental use is unlikely to cause acute device failure. However, evidence of material fatigue and micro-cracks warrants caution. This study highlights how expanding the use of existing devices, even beyond their original intent, may offer clinical benefits if properly evaluated. A literature review on haemodynamic considerations around arteriovenous VA (Chapter 4) revealed that there are currently no modalities available that substantially improve patency. This was further confirmed by a clinical study on a recently introduced external support device, that locks an AVF in an optimal hemodynamic angle (Chapter 5). This study concluded that although maturation could be improved, patency did not compared to a historic control group. The constantly supraphysiological flow causes vessel wall damage which ultimately leads to VA failure in or frequent secondary complications in many cases. Yet, patients typically only dialyse during 12 hours per week.
A implantable device was developed that can non-invasively open and close the arteriovenous connection using magnets (Chapter 6). This allows flow to be raised sufficiently for dialysis, but the circulation can be normalised otherwise. By removing the supraphysiological flow for most of the time, patency may be improved and complications reduced. Benchtop and cadaver studies showed feasibility of this device in non-invasively controlling the arteriovenous conduit. This device was included in a small number of animal studies, that focused on the in vivo development and iterative design improvement (Chapter 7). Although some issues remain in the design of the device, these animal studies demonstrated that the implant holds promise for tackling the core issue in vascular access for dialysis. However, future studies are necessary to establish long-term functionality and effects on disease outcomes.
End-stage kidney disease patients will continue to rely on haemodialysis due to limited treatments and donor kidneys. Their VA will remain their lifeline. Therefore, improving clinical outcomes of VA is of critical importance. A proposed device to open the high-flow conduit only during dialysis shows promise but involves significant development risks and long timelines. Interdisciplinary teams are essential to meet all user requirements. Advancing vascular access for haemodialysis requires sustained collaboration to develop, validate, and implement clinically grounded innovations for tangible patient benefits.