Elsevier

The Lancet

Volume 373, Issue 9673, 25 April–1 May 2009, Pages 1440-1446
The Lancet

Articles
Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study

https://doi.org/10.1016/S0140-6736(09)60248-8Get rights and content

Summary

Background

Application of a tissue-engineered vascular graft for small-diameter vascular reconstruction has been a long awaited and much anticipated advance for vascular surgery. We report results after a minimum of 6 months of follow-up for the first ten patients implanted with a completely biological and autologous tissue-engineered vascular graft.

Methods

Ten patients with end-stage renal disease who had been receiving haemodialysis through an access graft that had a high probability of failure, and had had at least one previous access failure, were enrolled from centres in Argentina and Poland between September, 2004, and April, 2007. Completely autologous tissue-engineered vascular grafts were grown in culture supplemented with bovine serum, implanted as arteriovenous shunts, and assessed for both mechanical stability during the safety phase (0–3 months) and effectiveness after haemodialysis was started.

Findings

Three grafts failed within the safety phase, which is consistent with failure rates expected for this high-risk patient population. One patient was withdrawn from the study because of severe gastrointestinal bleeding shortly before implantation, and another died of unrelated causes during the safety period with a patent graft. The remaining five patients had grafts functioning for haemodialysis 6–20 months after implantation, and a total of 68 patient-months of patency. In these five patients, only one intervention (surgical correction) was needed to maintain secondary patency. Overall, primary patency was maintained in seven (78%) of the remaining nine patients 1 month after implantation and five (60%) of the remaining eight patients 6 months after implantation.

Interpretation

Our proportion of primary patency in this high-risk cohort approaches Dialysis Outcomes Quality Initiative objectives (76% of patients 3 months after implantation) for arteriovenous fistulas, averaged across all patient populations.

Funding

Cytograft Tissue Engineering.

Introduction

Evolution of diagnostic tests (eg, electrocardiogram and CT angiography), drugs (eg, β blockers and statins), and interventional devices (eg, catheter-based technologies) has advanced cardiovascular medicine to an extent that few people could have imagined in the 1950s or 1960s. By contrast, the specialty of open vascular surgery has remained virtually unchanged. Modern techniques for peripheral and coronary bypass differ little from the first leg vascular bypass (1948) or the first successful coronary artery bypass (1967).1 Similarly, development of cardiovascular biomaterials has been surprisingly slow over the past 50 years.2 The expanded polytetrafluoroethylene (ePTFE) material used in Scribner's first chronic-use prosthetic blood vessel (1961) is essentially identical to the graft used nowadays, despite pronounced deficiencies compared with native veins or arteries.3, 4, 5, 6

Bell and colleagues7, 8 postulated that cell-seeded living grafts could be grown in vitro, which was the most radical advancement for prosthetic graft design. 20 years later, Shin'oka and colleagues9, 10 were the first to apply the theory clinically with successful use of cell-seeded polymers to repair congenital defects in the low-pressure pulmonary outflow tracts of paediatric patients. However, neither Shin'oka's nor Bell's approach had sufficient mechanical strength to warrant application of the graft to adult arterial bypass. Moreover, other researchers who used similar polymer-based approaches were unable to show clinically relevant burst strength with human cells.11, 12

We postulated that the application of cardiovascular biomaterials for tissue engineering has fundamental flaws because the synthetic or chemically modified scaffolds would interfere with, rather than guide, the natural assembly of key structural proteins. In 1998, we reported a new process called sheet-based tissue engineering and showed that with human cells, we could produce blood vessels with supraphysiological burst strength without the need for chemical modification, fixation, synthetic scaffolds, or exogenous biomaterials.13 We have since reported expanded preclinical results and the first human use of a completely biological tissue-engineered vascular graft.14, 15 In the first clinical report,14 we documented early (0–3 months) safety results for the first six patients implanted with the graft as an arteriovenous shunt for haemodialysis access, and we now present results of 6-month effectiveness for the full cohort of ten patients.

Section snippets

Patients

Ten patients with end-stage renal disease who had been receiving haemodialysis were enrolled from Instituto Argentino de Diagnóstico y Tratamiento, Buenos Aires, Argentina, and Department of General, Vascular, and Transplant Surgery, Katowice, Poland, between September, 2004, and April, 2007. All patients were older than 21 years and had had a previous haemodialysis access failure. All patients had a functioning access that the attending nephrologist and vascular surgeon judged to have a high

Results

Cells were successfully isolated from all patients and vessels were built with a mean burst pressure of 3512 mm Hg (SD 873, range 2348–4617). Ten patients with varying demographic indicators were enrolled in the study (table). Mean duration of haemodialysis before the study was 50·8 months (SD 31·6) at implantation. One patient withdrew from the study before implantation because of ill health; nine patients received the vascular graft and were monitored after implantation (figure 1).

Patient 1

Discussion

We have shown effective haemodialysis access with a completely biological and autologous vascular graft, which had primary patency in about three-quarters of patients 1 month after implantation and three-fifths of patients 6 months after implantation. Primary patency in this proportion of patients approaches the objectives of the Dialysis Outcomes Quality Initiative17 of about 76% 3 months after implantation across all patient populations for native vein fistulas.

Our arteriovenous shunt

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