New developments in dialysis grafts

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Ellen Dillavou
Ellen Dillavou

With the rising incidence of haemodialysis worldwide, there is an ever-increasing need for creative, durable means of access. The National Kidney Foundation and Centers for Medicare in the USA established the “Fistula Frist Breakthrough Initiative” in 2003, and revised this to “Fistula First, Catheter Last” in 2007 to encourage and educate dialysis care professionals about the need to avoid catheters and use fistulas whenever possible. Although the ideal would be to have all patients with working fistulae, this cannot be attained due to surface veins being insufficient or previously used in many patients. In this case, a dialysis graft may be the best solution, suggests Ellen D Dillavou, Durham, USA.

Prosthetic dialysis grafts have been used for decades, and they are generally easy to install, used soon (two weeks) after placement and cause little morbidity to place. The difficult part of graft use is the high incidence of thrombosis—more than 80% at one year in some series1–3—and propensity for infection—up to four times more than fistulae, but still less than catheters.

New developments

Coated grafts

Expanded polytetrafloroethylene (ePTFE) has been the standard for graft material for years. Recently here have been several updates to this material in hopes of making it more resistant to thrombosis and offering more flexible use patterns.

The Propaten grafts (Gore) are composed of ePTFE with a heparin-bonded coating. This coating is covalently bonded and is reported to last through the lifetime of the graft without providing systemic levels of anticoagulation. These grafts are available for dialysis access and extra-anatomic bypass. Although a theoretically promising addition to the dialysis access front, results with Propaten have not been significantly better then with non-heparinised grafts (see table). Additionally, care has to be taken to avoid implantation into patients with heparin-induced thrombocytopenia (HIT).

Immediate-use grafts

Four grafts are in testing or are available that provide immediate (within 72 hours) cannulation after placement. These grafts are useful for standard patients to facilitate early catheter removal, but also have several niche applications that are valuable tools for the access surgeon. One of these areas is graft revision, where an immediate-use product can be cannulated immediately to eliminate the need for a dialysis catheter placement while the graft replacement heals. Another useful application is in combination with the HeRO graft (Merit Medical) in patients with one functional deep venous access that pre-procedure has a dialysis catheter placed within that. In one operation the catheter can be rewired and a HeRO placed, and an immediate-use graft can then be sewn onto a stump of the HeRO PTFE graft, or the HeRO adapter can be used to clamp the HeRO and immediate-use graft together. The patient leaves the operating room with a functional, permanent access with drainage into their single central vein.

The Rapidax II (Terumo) is a three-layered graft that is 6mm, manufactured in both straight and looped configurations. It can be cannulated 24 hours after placement. A unique feature of the graft is that it can be antibiotic loaded by soaking in rifampin for five minutes prior to implantation. This graft is not yet available in the USA.

The Vectra (Bard PV) has been available worldwide for several years. This is available in 5mm and 6mm diameters and can be cannulated 24 hours after placement. It is supported by soft rings to resist compression and has sewing areas on each end that are not reinforced to facilitate anastomosis. A small trial demonstrated 42% one-year primary patency with a 10% infection rate in a high-risk population.4

The Acuseal (Gore) is a tri-layer graft with an inner gel that closes off needle holes. The graft comes in a straight 6mm or a 4–7mm taper configuration. The instructions for use suggest these can be cannulated 24 hours after placement, but they can in fact be used sooner than this with 17g needles at 250cc/min after a sterile prep. The Acuseal is heparin-coated, like the Propaten grafts, and therefore is not able to be used in patients with a history of HIT. One-year results showed a 35% primary and 79% secondary patency with an 11% infection rate and 11% steal rate. No differences in patency or complications were seen in patients who underwent early (<72 hours) versus late cannulation.5

The Flixene graft (Atrium) is 6mm in diameter and is available in trumpeted and pre-stented forms as well as in a straight configuration. This graft has four layers including a barrier layer to prevent extravasation with early cannulation. This graft can be used 72 hours after placement. In a prospective trial 78% of grafts were able to be used at 72 hours .3 The graft had a 34% primary and 51% secondary patency at 18 months.

Tissue-engineered grafts

Tissue-engineered grafts were first produced in the mid-1980s. These are composed of cells grown on synthetic or natural scaffolding that are then de-antigenised if not autologous. De-antigenised xenografts are also available.

Bovine carotid artery (Artegraft) is a collagen matrix graft that is a non-antigenic and is a de-cellularised conduit. Although the stated size of this graft is 6mm it can be larger than this diameter. This product is stored on the shelf and merely needs to be rinsed prior to use. At 12 months primary patency was 60% and secondary patency was 60%.6 This was significantly higher than the comparison ePTFE group.

The Procol (LeMaitre) graft has a high elasin-to-collegen ratio, giving it a great deal of pulsitility. This is a de-cellularised natural conduit made from bovine mesenteric vein and it is available in a 6mm diameter. It also stores on the shelf and can be rinsed immediately prior to use. In a multicentre trial primary patency was 36% at 12 months and secondary patency was 60% at 24 months. Secondary patency was significantly greater than the ePTFE comparison group, and this was thought to be due to greater infection resistance with the Procol graft and consequently less graft abandonment.7

De-antigenised cryopreserved human vein (SynerGraft, Cryolife) demonstrated comparable patency to ePTFE in small studies, so a randomised trial was attempted. However, this trial was stopped early due to high rates of fistulagrams and very resistant stenoses in the SynerGraft group.8 Due to these results this product is no longer marketed for dialysis access use.

The Humacyte graft (Humacyte)is a bioengineered vessel on a polymer scaffold base which is populated by human smooth muscle cells. Once the graft is confluent with cells it is de-cellularised and de-antigenised to leave the extracellular matrix behind. This is then implanted and over six months becomes populated with the patient’s endothelial and smooth muscle cells. This graft is available in a 6mm diameter. Phase II trial results in 60 patients showed a 12-month 28% primary patency and 89% secondary patency. There was no infection or pseudoaneurysm.9

As more attention is directed to dialysis access, new technology and full use of existing tools will allow quality care for difficult patients. Patient education and engagement is essential as we use these tools treat patients today and build upon this knowledge to craft solutions for tomorrow.

Primary 12 months Primary assisted at 12 months Secondary assisted at 12 months Primary at 36 months Primary assisted at 36 months Secondary assisted at 36 months
Propaten 14% 41% 83% 27% 81%
Standard ePTFE 12% 30% 73% 23% 68%
P value 0.48 0.12 0.33

References

  1. D Shemesh, I Goldin, J Hijazi, et al. J Vasc Surg 2015;v62(1):115–122
  2. GGD Maytham, HK Sran, ES Chemla. J Vasc Access 2015;16(6):467–471
  3. N Chiang, KR Hulme, PC Haggart, T Vasudevan. J Vasc Access 2014;15(2):116–122
  4. AF Schild, EA Perez , E Gillaspie, et al. Vasc Endovascular Surg 2007;41(6):506–8
  5. MH Glickman, J Burgess, D Cull, P Roy-Chaudhury, H Schanzer. J Vasc Surg 2015;62(2):434-41
  6. PT Kennealey, N Elias, M Hertl, et al. J Vasc Surg 2011;(6):1640–1648
  7. HE Katzman, MH Glickman, AF Schild, et al. J Am Coll Surg 2005;201:223–230
  8. RL Madden, GS Lipkowitz, BJ Browne et al. Ann Vasc Surg 2005;19:686
  9. JH Lawson, MH Glickman, M Ilzecki, et al. The Lancet 2016;387:2026–2034

Ellen D Dillavou is at Duke University Medical Center, Durham, USA