Five Year Outcomes in Patients with End Stage Renal Disease Who Received a Bioengineered Human Acellular Vessel for Dialysis Access

Objective: Patients with end stage renal failure who require haemodialysis suffer morbidity and mortality due to vascular access. Bioengineered human acellular vessels (HAVs) may provide a haemodialysis access option with fewer complications than other grafts. In a prospective phase II trial from 2012 to 2014 (NCT01744418), HAVs were implanted into 40 haemodialysis patients at three sites in Poland. The trial protocol for this “first in man” use of the HAV contemplated only two years of follow up, and the trial results were initially reported in 2016. In light of the retained HAV function seen in many of the patients at the two year time point, follow up for patients who were still alive was extended to a total of 10 years. This interim follow up report, at the long term time point of five years, assessed patient and conduit status in those who continued routine dialysis with the HAV

Methods: HAVs are bioengineered by culturing human vascular smooth muscle cells on a biodegradable polymer matrix. In this study, patients with patent HAV implants at 24 months were followed every three months, starting at month 27 through to month 60, or at least five years post-implantation. This report contains the follow up functional and histological data on 29 of the original 40 patients who demonstrated HAV function at the 24 month time point.

Results: Eleven patients completed at month 60. One patient maintained primary patency, and 10 maintained secondary patency. Secondary patency was estimated at 58.2% (95% confidence interval 39.2e73.1) at five years, after censoring for deaths (n ¼ 8) and withdrawals (n ¼ 1). No HAV conduit infections were reported during the follow up period.

Conclusion: This phase II long term follow up shows that the human acellular vessel (HAV) may provide durable and functional haemodialysis access for patients with end stage renal disease.
2022 The Authors. Published by Elsevier Ltd on behalf of European Society for Vascular Surgery. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Article history: Received 15 May 2021, Revised 1 November 2021, Accepted 4 January 2022,

Keywords: Blood vessel prosthesis, Haemodialysis, Regenerative medicine, Tissue engineering, Vascular access

INTRODUCTION End stage renal disease (ESRD) patients who are not candidates for autogenous fistulas or whose fistulas have failed, rely on synthetic arteriovenous (AV) grafts (e.g., expanded polytetrafluoroethylene [ePTFE]) for vascular access. However, synthetic grafts have higher infection and stenosis rates than AV fistulas.1e6 Loss of primary unassisted patency in ePTFE grafts occurs in up to 75% of patients by one year,6 and long term patency rates are approximately 27% at five years.7 Graft and fistula failure can force patients to rely on central venous catheters, which are associated with higher rates of infection, all cause mortality, and cardiovascular events.

Biological alternatives may offer improved benefits over other grafts; however, to date, no biological conduits (e.g., xenografts such as Artegraft [LeMaitre Vascular, Burlington, MA, USA] and ProCol [LeMaitre]) have gained wide clinical adoption.3,10e12 The human acellular vessel (HAV), a novel bioengineered alternative for dialysis access, has been reported previously.

The clinical use of the HAV was reported in 60 ESRD subjects over one year (40 in Poland, 20 in the USA) from two phase II trials (NCT01744418 and NCT01840956).13 Since then, the patients have continued routine dialysis with the HAV. A long term follow up to 10 years postimplantation was added for the original Polish 40 patient cohort (NCT01744418). (For the 20 patient US cohort, Institutional Review Board approval for an extended follow up beyond two years was not requested.) The objective of this report was to provide data on the long term function of HAVs that were implanted into haemodialysis subjects from the Polish trial (NCT0174418), for at least five years of follow up. To the best of the authors’ knowledge, this is the longest follow up of any engineered human connective tissue used in a clinical setting. More