title: Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials.
abstract: BACKGROUND
  For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access.
  
  
  METHODS
  We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956.
  
  
  RESULTS
  Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency.
  
  
  CONCLUSIONS
  Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials.
  
  
  BACKGROUND
  Humacyte and US National Institutes of Health.
authors.affiliation: Humacyte, Durham, NC, USA; Duke University, Durham, North Carolina, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lawson
authors.affiliation: Humacyte, Durham, NC, USA; Sentara Heart Hospital, Norfolk, VA, USA.
authors.forename: Marc H
authors.initials: MH
authors.lastname: Glickman
authors.affiliation: Department of Vascular Surgery and Angiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Ilzecki
authors.affiliation: Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jakimowicz
authors.affiliation: Department of Family Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jaroszynski
authors.affiliation: Cardiovascular Surgery Associates, Houston, TX, USA.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Peden
authors.affiliation: Humacyte, Durham, NC, USA.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Pilgrim
authors.affiliation: Humacyte, Durham, NC, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Prichard
authors.affiliation: Research and Development Centre, Vascular Surgery Department, General Hospital in Wrocław, Wrocław, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Guziewicz
authors.affiliation: Department of Vascular Surgery and Angiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Przywara
authors.affiliation: Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Szmidt
authors.affiliation: Research and Development Centre, Vascular Surgery Department, General Hospital in Wrocław, Wrocław, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Turek
authors.affiliation: Research and Development Centre, Vascular Surgery Department, General Hospital in Wrocław, Wrocław, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Witkiewicz
authors.affiliation: Research and Development Centre, Vascular Surgery Department, General Hospital in Wrocław, Wrocław, Poland.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zapotoczny
authors.affiliation: Department of Vascular Surgery and Angiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zubilewicz
authors.affiliation: Department of Anesthesia & Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: laura.niklason@yale.edu.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
mesh_terms: D057005:Bioengineering; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D011138:Polytetrafluoroethylene / Q000627:therapeutic use; D011474:Prosthesis Design; D006435:Renal Dialysis / Q000295:instrumentation*; D062666:Vascular Access Devices
chemical_list: D011138:Polytetrafluoroethylene