Abstract 466: CX3CR1 Down Regulation Reduces Venous Neointimal Hyperplasia Formation in a Murine Hemodialysis Vascular Access Model

Introduction: Venous neointimal hyperplasia (VNH) is a major cause of hemodialysis arteriovenous fistula (AVF) vascular access failure. CX3CR1 mediates macrophage infiltration into the vasculature. Mice were used which had been genetically engineered to knock in the human CX3CR1 gene. Hypothesis: The hypothesis to be tested is that increased CX3CR1 gene expression results in VNH formation associated with AVF. Methods: We used 50 CX3CR1 knock in mice which were divided into 2 groups: 1. CX3CR1 antibody (30 mg/kg administered intraperitoneally two times per week) or vehicle (equal amount of volume used for CX3CR1 antibody administered intraperitoneally). AVFs were created by connecting the carotid artery to ipsilateral jugular vein 28 days after nephrectomy was performed to induce chronic kidney disease. Histology and Immunohistochemistry analysis at the outflow vein of AVF were performed to assess the pathological changes. Results: There was a significant decrease in neointima area in the outflow veins of AVF in CX3CR1 antibody group compared to the vehicle group at day 28 (43085 ± 12678 vs. 58963.4 ± 9273 μm 2 , P<0.05). There was a significant decrease in the ratio of neointima/media+adventitia area in the outflow veins of AVF in CX3CR1 antibody group compared to the vehicle group at day 28 (0.34 ± 0.1 vs. 0.61 ± 0.1, P<0.05). Cell density in neointima area in CX3CR1 group outflow veins was significantly lower than the vehicle group at day 14 (9600 ± 1000 vs. 13000 ± 3000 /mm 2 , P<0.01). There was a significant decrease in the average CD68-positive cell density in the CX3CR1 group outflow veins compared to the vehicle group (0.96 ± 0.34 vs.15.9 ±10, P<0.001) at day 14. Conclusion: Decreasing CX3CR1 significantly reduces macrophages infiltration and results in a significant reduction in VNH. This study provides a rationale for using CX3CR1 antibody in reducing VNH formation.

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Minimizing Hemodialysis Vascular Access Trauma with an Improved Needle Design

Journal of the American Society of Nephrology ◽

10.1681/asn.v1171325 ◽

2000 ◽

Vol 11 (7) ◽

pp. 1325-1330

Author(s):

EDWARD A. ROSS ◽

JILL W. VERLANDER ◽

LILIA C. KOO ◽

IRVIN F. HAWKINS

Keyword(s):

Carotid Artery ◽

Vascular Access ◽

Neointimal Hyperplasia ◽

Graft Material ◽

Dialysis Tubing ◽

Fresh Tissue ◽

Synthetic Materials ◽

Hemodialysis Vascular Access ◽

Longitudinal Strength ◽

Repetitive Trauma

Abstract. The maintenance and longevity of hemodialysis vascular access remains one of the most problematic topics in the care of dialysis patients. Although much attention has focused on neointimal hyperplasia, the repetitive trauma to vessel walls by dialysis needles causes significant cumulative damage that has undergone little investigation. Commercial needles have beveled tips with intentional cutting surfaces to ease insertion. It was hypothesized that a pencil-point conical-shaped needle would cause less damage by taking advantage of the elasticity of native fistulae and produce an improved hole configuration in synthetic materials with minimal ability to stretch. A needle was subsequently designed with a removable pencil-point trocar and a side arm for the dialysis tubing. Once the trocar is removed, the blunt-ended cannula can be advanced or can be subject to inadvertent motion without causing damage to the luminal surface of the access. The new design as well as standard 15-gauge hemodialysis needles were tested on Gore-Tex® graft material and two bovine carotid artery preparations. Scanning electron microscopy was used to study the hole patterns. For all materials, the commercial needle holes had typical crescent shapes, and the cuts sliced sequentially through the various layers. For grafts, the new design caused a linear defect parallel to the axis of the graft that may preserve longitudinal strength. Interestingly, that tear line was nearly perpendicular to the linear hole in the thin polytetrafluoroethylene overwrap, which would be consistent with maintenance of hoop integrity. It is believed that these nonoverlapping defects would also improve hemostasis. The bovine specimens tested the importance of tissue stretching : Fresh carotid artery had experimental holes dramatically smaller than those from standard needles. In the denatured tissue, the experimental needle provided less benefit than that observed in fresh tissue, which is likely due to limited elasticity of the preserved artery. Improvement in needle design thus provides distinct advantages for native vessels and unique less traumatic holes in current synthetic materials. Pencil-point needle designs may be particularly applicable to the development of new elastomeric graft material.

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Genetic Causation of Neointimal Hyperplasia in Hemodialysis Vascular Access Dysfunction

Seminars in Dialysis ◽

10.1111/j.1525-139x.2011.00967.x ◽

2011 ◽

Vol 25 (1) ◽

pp. 65-73 ◽

Cited By ~ 9

Author(s):

Timmy Lee ◽

Davinder Wadehra

Keyword(s):

Vascular Access ◽

Neointimal Hyperplasia ◽

Hemodialysis Vascular Access

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The role of stents in hemodialysis vascular access

The Journal of Vascular Access ◽

10.1177/11297298211015069 ◽

2021 ◽

pp. 112972982110150

Author(s):

Aisha Shaikh ◽

Alian Albalas ◽

Brinda Desiraju ◽

Amy Dwyer ◽

Nabil Haddad ◽

...

Keyword(s):

Vascular Access ◽

Neointimal Hyperplasia ◽

Transluminal Angioplasty ◽

Hemodialysis Vascular Access ◽

Clinical Scenarios ◽

Anatomic Locations ◽

End Stage ◽

Percutaneous Transluminal ◽

Stenotic Lesions

Vascular access is the Achilles’ heel of dialysis therapy among patient with end stage kidney disease. The development of neointimal hyperplasia and subsequent stenosis is common in vascular access and is associated with significant morbidity. Percutaneous transluminal angioplasty using balloon inflation was the standard therapy of these lesions. However, the balloon-based approaches were associated with poor vascular access patency rate necessitating new inventions. It is within this context that different types of stents were developed in order to improve the overall dialysis vascular access functionality. In this article, we review the available literature regarding the use of stents in treating dialysis vascular access stenotic lesions. Further, we review the major clinical trials of stent use in different anatomic locations and in different clinical scenarios.

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Endothelial Progenitor Cells, Neointimal Hyperplasia, and Hemodialysis Vascular Access Dysfunction

Circulation ◽

10.1161/circulationaha.105.548651 ◽

2005 ◽

Vol 112 (1) ◽

pp. 3-5 ◽

Cited By ~ 28

Author(s):

Prabir Roy-Chaudhury

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Vascular Access ◽

Neointimal Hyperplasia ◽

Endothelial Progenitor ◽

Hemodialysis Vascular Access

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Rationale and Trial Design of MesEnchymal Stem Cell Trial in Preventing Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula (MEST AVF Trial)

Kidney360 ◽

10.34067/kid.0005182021 ◽

2021 ◽

pp. 10.34067/KID.0005182021

Author(s):

Ameet K. Piryani ◽

Sreenivasulu Kilari ◽

Edwin Takahashi ◽

Randall R. DeMartino ◽

Jay Mandrekar ◽

...

Keyword(s):

Upper Extremity ◽

Vascular Access ◽

Trial Design ◽

Phase 1 ◽

Neointimal Hyperplasia ◽

Ongoing Trial ◽

Arteriovenous Fistulas ◽

Venous Stenosis ◽

Hemodialysis Vascular Access ◽

Fistula Maturation

Background: Hemodialysis arteriovenous fistulas (AVFs) are the preferred vascular access for patients on hemodialysis. In the Hemodialysis Fistula Maturation Study, 43.7% of the patients achieved unassisted maturation of their fistula without needing an intervention. Venous neointimal hyperplasia (VNH) and subsequent venous stenosis (VS) is responsible for lack of maturation. There are no therapies that can prevent VNH/VS formation. The goal of this paper is to present the background, rationale, and trial design of an innovative phase 1 / 2 clinical study that is investigating the safety of autologous adipose derived mesenchymal stem cells (AMSCs) delivered locally to the adventitia of newly created upper extremity radiocephalic (RCF) or brachiocephalic fistula (BCF). Methods: The rationale and pre-clinical studies used to obtain a physician sponsored investigational new drug trial (IND) are discussed. The trial design and endpoints are discussed. Results: This is ongoing trial which will complete this year. Conclusion: This is a phase 1 / 2 single center, randomized trial which will investigate safety and efficacy of autologous AMSCs in promoting maturation in new upper extremity AVFs.

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