Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts

Osborn, Gary; Escofet, Xavier; Silva, Anthony Da

doi:10.1002/14651858.cd002786.pub2

Cited by 45 publications

(36 citation statements)

References 20 publications

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“…Because of that and the persistently high rates of A-V fistula failures, the initiative has not reduced the costs of medical interventions to salvage stenosed fistulae as it was intended (29). In addition, anticoagulant-and antiplatelet-based pharmacological treatments to promote and maintain patency of this type of vascular access have limited impact (10,37), in part because they do not target the formation of NIH, which is the underlying cause of fistula stenosis. This study shows for the first time that inhibition of c-Kit, a target for which there is an existing translatable platform for drug development, effectively prevents neointima formation in experimental A-V fistulae in rodents.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Anticoagulation may reduce graft failure in patients with this genotype [40] . Osborn et al [41] in their meta-analysis report the beneficial effect of anti-platelet treatment as an adjuvant used to increase the patency of A-V fistulae and grafts in the short term. Paulson et al [42] state that current evidence does not support the concept that all accesses should undergo routine surveillance with intervention.…”

Section: Permanent Vamentioning

confidence: 99%

Vascular access today

Pantelias

Grapsa²

2012

WJN

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The number of patients with chronic kidney disease requiring renal replacement therapy has increased worldwide. The most common replacement therapy is hemodialysis (HD). Vascular access (VA) has a key role for successful treatment. Despite the advances that have taken place in the field of the HD procedure, few things have changed with regards to VA in recent years. Arteriovenous fistula (AVF), polytetrafluoroethylene graft and the cuffed double lumen silicone catheter are the most common used for VA. In the long term, a number of complications may present and more than one VA is needed during the HD life. The most common complications for all of VA types are thrombosis, bleeding and infection, the most common cause of morbidity in these patients. It has been estimated that VA dysfunction is responsible for 20% of all hospitalizations. The annual cost of placing and looking after dialysis VA in the United States exceeds 1 billion dollars per year. A good functional access is also vital in order to deliver adequate HD therapy. It seems that the native AVF that Brescia and Cimino described in 1966 still remains the first choice for VA. The native forearm AVFs have the longest survival and require the fewest interventions. For this reason, the forearm AVF is the first choice, followed by the upper-arm AVF, the arteriovenous graft and the cuffed central venous catheter is the final choice. In conclusion, VA remains the most important issue for patients on HD and despite the technical improvements, a number of problems and complications have to be resolved.

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“…It is not possible to prevent the emergence of VAG. Antiplatelet and anticoagulant therapy do not significantly prevent the risk of graft thrombosis 10,11 . Prevention of thrombosis of AVGs with anticoagulant therapy is associated with high risk of bleeding while the effect of graft thrombogeneity is uncertain 12 .…”

Section: Introductionmentioning

confidence: 99%

Arteriovenous graft for hemodialysis, graft venous anastomosis closure - current state of knowledge. Minireview

Bachleda¹,

Utíkal²,

Köcher³

et al. 2015

BIOMED PAP

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aBackround. The use of artificial vascular grafts (arteriovenous graft, AVG) is indicated in patients in hemodialysis programs if the subcutaneous venous bed is exhausted or unsuitable for arteriovenous fistula (AVF) creation. The native fistula should be the hemodialysis access of first choice: AVF has better results in terms of function and potential complications. However, the use of AVG is necessary in some patients. In these patients, extensive clinical examination, color duplex sonography and angiography should be performed prior to indication. The technique of graft implantation requires respect for geometric relations for the graft anastomoses to minimize the formation of intimal hyperplasia mainly on the venous anastomosis. The main complications of AVG are stenosis on the venous anastomosis (VAG), causing closure of graft and graft infection. The cumulative function of AVG is 59-90% in the first year and 50-82% in the second year. Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. The purpose of this review is to summarise current knowledge of the diagnostics and treatment of graft thrombosis and discuss the issue in combination with relevant publications via Pubmed database. Conclusion. The most frequent cause of failure of AVG for hemodialysis is stenosis and closure by VAG. AVG closure can be addressed surgically, endovascularly (amenable to thrombectomy by radiological or surgical means) and by hybrid performance.

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Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts

Cited by 45 publications

References 20 publications

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Vascular access today

Arteriovenous graft for hemodialysis, graft venous anastomosis closure - current state of knowledge. Minireview

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