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Challenges and novel therapies for vascular access in haemodialysis

Abstract

Advances in standards of care have extended the life expectancy of patients with kidney failure. However, options for chronic vascular access for haemodialysis — an essential part of kidney replacement therapy — have remained unchanged for decades. The high morbidity and mortality associated with current vascular access complications highlights an unmet clinical need for novel techniques in vascular access and is driving innovation in vascular access care. The development of devices, biological approaches and novel access techniques has led to new approaches to controlling fistula geometry and manipulating the underlying cellular and molecular pathways of the vascular endothelium, and influencing fistula maturation and formation through the use of external mechanical methods. Innovations in arteriovenous graft materials range from small modifications to the graft lumen to the creation of completely novel bioengineered grafts. Steps have even been taken to create new devices for the treatment of patients with central vein stenosis. However, these emerging therapies face difficult hurdles, and truly creative approaches to vascular access need resources that include well-designed clinical trials, frequent interaction with regulators, interventionalist education and sufficient funding. In addition, the heterogeneity of patients with kidney failure suggests it is unlikely that a ‘one-size-fits-all’ approach for effective vascular access will be feasible in the current environment.

Key points

  • Globally, effective treatment of kidney failure depends on reliable vascular access so that patients can receive long-term kidney replacement therapy.

  • Current vascular access options are arteriovenous fistula, graft or central venous catheter, each of which is associated with high mortality, morbidity and economic burden.

  • For fistulas, new devices, biological approaches and techniques are in development that control fistula geometry, manipulate underlying cell and molecular pathways and influence maturation.

  • New graft and catheter materials are also in development, encompassing both incremental changes in current technologies and novel bioengineered vascular materials.

  • Process of care innovations are also important in order to generate patient-centred approaches that will be applicable to all individuals with kidney failure.

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Fig. 1: Current vascular access routes for haemodialysis.
Fig. 2: Clinical manifestations of vascular access dysfunction.
Fig. 3: Regional differences in the use of different vascular access modalities.
Fig. 4: Health disparities in vascular access.
Fig. 5: Innovations in approaches to manipulating fistula geometry and haemodynamics.
Fig. 6: Innovations in graft materials.
Fig. 7: Innovation in vascular access and process of care.

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Acknowledgements

The authors acknowledge the support of K.L. Hamilton (Humacyte, Inc., Durham, NC, USA) in collating information and references for this article.

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The authors contributed equally to all aspects of the article.

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Correspondence to Jeffrey H. Lawson.

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Competing interests

J.H.L. is the CEO of Humacyte, Inc. and is a co-founder of InnAVasc. L.E.N. is the founder of Humacyte, Inc. P.R.-C. is a consultant and adviser for WL Gore, BD, Medtronic, Cormedix, Humacyte, Akebia, Vifor-Relypsa and Bayer; the founder and Chief Scientific Officer of Inovasc LLC; the founding co-chair of the Kidney Health Initiative; and currently a member of the steering committee of the KidneyX Innovation Accelerator. P.R.-C. is also a co-PI on phase II of NIH Small Business award programs with Cylerus.

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Glossary

Maturation

Maturation in the context of fistula maturation is a dynamic remodelling process whereby the vascular wall thickens and the vein dilates in size to allow regular cannulation and blood flow for haemodialysis. Thrombosis, stenosis and poor blood flow can all contribute to a lack of clinical maturation.

Juxta-anastomotic stenosis

Narrowing of the vessel at and around the anastomosis, typically due to neointimal hyperplasia. Juxta-anastomotic stenosis (that is, stenosis on the venous side within 3 cm of the anastomosis) is part of a larger collective term, ‘peri-anastomotic stenosis’, which also includes anastomotic stenosis and arterial stenosis.

Secondary patency

The time from access placement until access abandonment or thrombosis, or the time from measurement of patency including intervening manipulations (surgical or endovascular interventions) designed to re-establish functionality in a thrombosed access.

AV fistula aneurysm

A true arteriovenous (AV) fistula aneurysm is defined as an abnormal vessel dilation that may burst if not treated. The definition of a true AV access aneurysm is still under debate, but one proposed definition is an increase in vessel diameter of at least 50% with true dilation of all layers of the vessel wall.

Primary patency

The time from access placement until any intervention designed to maintain or re-establish patency, access thrombosis, or the time from measurement of patency.

Piggyback straight-line onlay technique

A fistula creation technique where the vein ‘piggybacks’ on the artery at the site of anastomosis, and the arterial blood flows into a straight cylindrical lumen. The cephalic vein in the subcutaneous plane is dissected and divided, and the cut end is over-sewn with prolene; it is moved medially over the artery, which lies in a deeper plane. A fistula is created between the posterior aspect of the vein and the anterior aspect of the artery. The outflow vein is dissected further in the subcutaneous tissue to obtain a straight line.

End-to-side techniques

Techniques in which the fistula is formed by connecting the end of the vein to the side of the artery. This is the most common technique for creation of a radiocephalic fistula by connecting the end of the cephalic vein to the side of the radial artery.

Plain old balloon angioplasty

(POBA). Also known as classic balloon angioplasty, this technique mechanically widens narrowed vessels by using a balloon to dilate the identified stenosis.

Bovine carotid artery (BCA) grafts

A BCA graft (such as the Artegraft (Artegraft, Inc.)) is a xenograft used for vascular access in haemodialysis. These biological conduits are chemically fixed bovine carotid arteries, and no longer have the ability to remodel, repopulate with host cells or heal.

Infiltration

Migration of cells from the outer layer of the blood vessel to the inner layers that mainly impacts inward remodelling and/or the development of neointimal hyperplasia.

CE Mark

A certification used in the European Union (EU) to indicate that devices conform with health, safety and environmental standards set by the European Commission for products sold in the European Economic Area (EEA). Many devices require CE marking before they are able to be sold in the EU.

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Lawson, J.H., Niklason, L.E. & Roy-Chaudhury, P. Challenges and novel therapies for vascular access in haemodialysis. Nat Rev Nephrol 16, 586–602 (2020). https://doi.org/10.1038/s41581-020-0333-2

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