Severe venous neointimal hyperplasia prior to dialysis access surgery

Lee, Timmy; Chauhan, Vibha; Krishnamoorthy, Mahesh; Wang, Yan; Arend, Lois J.; Mistry, Meenakshi J.; El-Khatib, Mahmoud; Banerjee, Rupak K.; Munda, Rino; Roy‐Chaudhury, Prabir

doi:10.1093/ndt/gfq733

Cited by 105 publications

(124 citation statements)

References 32 publications

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“…It is known that the uremic milieu in patients with end stage renal disease contributes to a multitude of vascular diseases including venous intimal hyperplasia even prior to hemodialysis access surgery [14][15][16] . This present model does not incorporate the uremic milieu.…”

Section: Representative Resultsmentioning

confidence: 99%

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

Wong

Vries

Wang

et al. 2016

JoVE

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The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the exact pathophysiology remains unknown. In order to unravel the pathophysiology a murine model of AVF-failure was developed in which the configuration of the anastomosis resembles the preferred situation in the clinical setting. A model was described in which an AVF is created by connecting the venous end of the branch of the external jugular vein to the side of the common carotid artery using interrupted sutures. At a histological level, we observed progressive stenotic intimal lesions in the venous outflow tract that is also seen in failed human AVFs. Although this procedure can be technically challenging due to the small dimensions of the animal, we were able to achieve a surgical success rate of 97% after sufficient training. The key advantage of a murine model is the availability of transgenic animals. In view of the different proposed mechanisms that are responsible for AVF failure, disabling genes that might play a role in vascular remodeling can help us to unravel the complex pathophysiology of AVF failure. Video LinkThe video component of this article can be found at

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Section: Representative Resultsmentioning

confidence: 99%

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

Wong

Vries

Wang

et al. 2016

JoVE

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“…Of note, these therapies will be limited to prevent postsurgical NIH and not preexisting neointimal lesions in the vein. The existence of preexisting NIH in veins of hemodialysis patients has been recently described, and its presence is not associated with A-V fistula outcomes (1,3,24). …”

Section: Discussionmentioning

confidence: 98%

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Skartsis

Martinez

Duque

et al. 2014

American Journal of Physiology-Renal Physiology

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Skartsis N, Martinez L, Duque JC, Tabbara M, Velazquez OC, Asif A, Andreopoulos F, Salman LH, Vazquez-Padron RI. c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae. Am J Physiol Renal Physiol 307: F1095-F1104, 2014. First published September 3, 2014 doi:10.1152/ajprenal.00292.2014.-Stenosis of arteriovenous (A-V) fistulae secondary to neointimal hyperplasia (NIH) compromises dialysis delivery, which worsens patients' quality of life and increases medical costs associated with the maintenance of vascular accesses. In the present study, we evaluated the role of the receptor tyrosine kinase c-Kit in A-V fistula neointima formation. Initially, c-Kit was found in the neointima and adventitia of human brachiobasilic fistulae, whereas it was barely detectable in control veins harvested at the time of access creation. Using the rat A-V fistula model to study venous vascular remodeling, we analyzed the spatial and temporal pattern of c-Kit expression in the fistula wall. Interestingly, c-Kit immunoreactivity increased with time after anastomosis, which concurred with the accumulation of cells in the venous intima. In addition, c-Kit expression in A-V fistulae was positively altered by chronic kidney failure conditions. Both blockade of c-Kit with imatinib mesylate (Gleevec) and inhibition of stem cell factor production with a specific short hairpin RNA prevented NIH in the outflow vein of experimental fistulae. In agreement with these data, impaired c-Kit activity compromised the development of NIH in A-V fistulae created in c-Kit W/Wv mutant mice. These results suggest that targeting of the c-Kit signaling pathway may be an effective approach to prevent postoperative NIH in A-V fistulae. arteriovenous fistula; hemodialysis; neointima THE ARTERIOVENOUS (A-V) fistula is the preferred type of vascular access for hemodialysis patients (29). It achieves higher patency rates, has fewer complications than synthetic grafts (12,29,31), and has a lower risk of infections than central venous catheters (17,29). Despite its advantages, A-V fistulae frequently fail to mature or become dysfunctional after successful dialysis sessions, and this occurs primarily due to the development of neointimal hyperplasia (NIH) within the A-V fistula circuit (2, 5, 39). Stenosed A-V fistulae can sometimes be salvaged through angioplasty or surgical interventions, but these attempts often result in restenosis or additional complications (32). Therefore, there is an unmet medical need for treatments that prevent NIH and improve A-V fistula function. To this end, it is necessary to better define the factors underlying the pathological remodeling of the A-V fistula wall.A-V fistula maturation is a dynamic vascular process with multiple factors contributing to the development of NIH. These include vein configuration (22) In the present study, we investigated the role of c-Kit in the pathological remodeling of A-V fistulae. We show that activation of the c-Kit signaling pathway in adventitial and neointimal cells precedes arteri...

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“…Although it is unlikely that postoperative IH alone leads to critical AVF occlusion (10), it may be a contributing factor to AVF nonmaturation in the setting of inadequate outward remodeling. More recently, IH has been also identified as a common preexisting (13,14). These studies emphasized the profound histologic differences between preexisting and postoperative IH ( Figure 1).…”

Section: Ih Pathobiology Of Preexisting Ihmentioning

confidence: 92%

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

Vázquez-Padrón

Allon

2016

CJASN

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Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.

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Severe venous neointimal hyperplasia prior to dialysis access surgery

Cited by 105 publications

References 32 publications

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

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