Regenerative material found “safe and feasible” for haemodialysis access in first-in-human study

The advantages of autogenous fistulas to haemodialysis patients include long-term survival and low rates of complication. But failed or slow maturation as well as the risk of early thrombosis frequently “offset” these advantages and result in the use instead of a central venous catheter. Such “serious limitations”, write the authors of a new study published in the Journal of Vascular Access (JVA), demand the evaluation of alternative options.

Among those are biological regenerative conduits. Lead author Adrian Ebner (Sanatorio Italiano, Asuncion, Paraguay), alongside fellow researchers including Haimanot Wasse (Rush Medical College, Chicago, USA) and corresponding author Zeeshan Syedain (University of Minnesota, Twin Cities, USA), focused on the TRUE AVC (Vascudyne) tissue-engineered vascular conduit and examined whether it could demonstrate “functional patency, lack of infection, and a low adverse event rate”.

Ebner et al’s new study is among the first to focus on a novel tissue-engineered vascular conduit “cultured from completely biologic raw materials and allogeneic dermal cells”, which had previously been trialled in non-human primate models. That trial found no immune response, while “dialysis needle puncture sites demonstrated normal healing with no reduction in mechanical strength of the conduit”. This study, meanwhile, follows on from the work of Jeffrey H Lawson (Duke University, Durham, USA) and colleagues in a Lancet-published investigation from 2016, which found that a bioengineered human acellular vessel “seem[ed] to provide safe and functional haemodialysis access”, suggesting a potential step up from polytetrafluoroethylene arteriovenous grafts and their associated thrombosis and infection risks.

Building on this, Ebner and colleagues designed their first-in-human study to look at the outcomes from five patients who received an implant of the conduit “in an initial evaluation of [its] clinical safety and performance”. Patients were selected if they were aged 18–75, diagnosed with end-stage kidney disease (ESKD)—although one selected was pre-ESKD—and either on dialysis or intended to initiate it within 12 weeks.

Primary efficacy endpoints of the study were primary patency, assisted primary patency, and secondary patency at 26 weeks, plus successful dialysis through to six months. Ultrasound and physical examination were used for assessment. Among the secondary endpoints was immune system response to the implant, while primary safety endpoints included freedom from clinically significant aneurysm and anastomotic bleeding.

The authors state that the conduit “handled well surgically, with properties similar to that of the native human vein”. Conduit flow following the procedure was “excellent in all cases,” meanwhile, “averaging 1098±388ml/min at week four and remaining stable through 1248±355ml/min at 26 weeks”. There was no significant change in surgical site healing compared to regular conduits, with no oedema or erythema found at four weeks. Primary patency at six months was found to be 80%, with secondary patency recorded at 100%. There was no infection in any of the patients, all of whom received dialysis, nor was there statistically significant change in the diameter of the conduit on ultrasound examination. The authors also note that “no specific IgG antibody response was seen in any patients”, and add that one patient required reintervention for thrombus removal at five months.

Ebner and colleagues say the results demonstrate “the initial and early safety of TRUE AVC”. Speaking exclusively to Renal Interventions, Syedain added: “Completely biological regenerative tissue conduits are designed to mimic the structure and function of natural blood vessels, potentially improving longevity and performance of haemodialysis grafts. This study demonstrates initial safety, mechanical durability and lack of immune response with TRUE AVC, and its potential as an off-the-shelf blood vessel conduit for clinical use.”

Looking forward, Ebner et al point out that larger cohort studies are planned to further investigate the safety and efficacy of TRUE AVC.