Plasma ADMA Predicts Restenosis of Arteriovenous Fistula

Wu, Chih‐Cheng; Wen, Szu Chi; Yang, Chung-Wei; Pu, Shih Yun; Tsai, Kuei Chin; Chen, Jaw Wen

doi:10.1681/asn.2008050476

Cited by 40 publications

(55 citation statements)

References 49 publications

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“…The reasons for this endothelial dysfunction include increased oxidative stress, the presence of NO inhibitors such as asymmetric dimethylargine (AMDA) and a reduced number and function of endothelial progenitor cells [164]. AMDA accumulates with progressive CKD, and high levels are associated with aggressive restenosis after angioplasty [165]. AMDA and glycation end products (AGE) lead to decreased NO bioavailability, impairing arterial dilation as well as impairing NO-related signaling [166].…”

Section: Mechanisms Contributing To Avf Maturation and Failurementioning

confidence: 99%

Future research directions to improve fistula maturation and reduce access failure

Patel

Hänisch

et al. 2016

Seminars in Vascular Surgery

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With the increasing prevalence of end stage renal disease there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes, in the setting of uremia, systemic inflammation, oxidative stress and preexistent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis, as well as development of neointimal hyperplasia (NIH) that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to NIH involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure, based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure requires a multidisciplinary approach involving nephrologists, vascular surgeons and interventional radiologists, allowing careful patient selection and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy.

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Section: Mechanisms Contributing To Avf Maturation and Failurementioning

confidence: 99%

Future research directions to improve fistula maturation and reduce access failure

Patel

Hänisch

et al. 2016

Seminars in Vascular Surgery

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“…51 Finally, as shown in recent studies, in hemodialysis patients undergoing angioplasty of stenotic AVFs, higher plasma levels of ADMA are strongly predictive of the risk for restenosis. 52 The femoral AVF model in the rat, as described in the present and recent studies, 11,14,53 complements other rodent models used to study AVF failure. For example, the murine AVF model recapitulates the salient features of dysfunctional and failing human AVFs, 10 and when created in genetically altered mice, allows the interrogation of the functional significance of specific genes; this murine model was recently used in the examination of the pathobiologic significance of heme oxygenase-1 12 and osteopontin in an AVF, 13 and the therapeutic efficacy of bone morphogenetic protein 7 in this murine model when created in mice with chronic kidney disease.…”

Section: Discussionmentioning

confidence: 78%

Characterization of a Model of an Arteriovenous Fistula in the Rat

Croatt

Grande

Hernandez

et al. 2010

The American Journal of Pathology

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Vascular access dysfunction contributes to the mortality of patients undergoing chronic hemodialysis. The present study analyzed the changes that evolve in a femoral arteriovenous fistula in the rat. The venous segment of this model exhibited, at 1 week, activation of pro-inflammatory transcription factors and up-regulation of pro-inflammatory , proliferative , procoagulant, and profibrotic genes; and at 4 weeks, the venous segment displayed neointimal hyperplasia, smooth muscle proliferation, and thrombus formation. These changes were accompanied by endothelial (e) nitric oxide synthase (NOS) and inducible (i) NOS up-regulation. The administration of N G -nitro-L-arginine methyl ester, an inhibitor of NOS activity, increased venous neointimal hyperplasia and pro-inflammatory gene expression (monocyte chemoattractant protein؊1 and cytokine-induced neutrophil chemoattractant-1), increased systolic blood pressure, and decreased blood flow through the fistula. In another hypertensive model, the rat subtotal nephrectomy model, venous neointimal hyperplasia in the arteriovenous fistula was also exacerbated. We conclude that this arteriovenous fistula model recapitulates the salient features observed in dysfunctional, hemodialysis arteriovenous fistulas, and that venous neointimal hyperplasia is exacerbated when this model is superimposed in two different models of systemic hypertension. Since the uremic milieu contains increased amounts of asymmetric dimethylarginine , we speculate that such accumulation of this endogenous inhibitor of NOS , by virtue of its pressor or nitric oxide-depleting effects , or a combination thereof , may contribute to the limited longevity of arteriovenous fistulas used for hemodialysis.

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“…19 Serum indoxyl sulfate levels are, thus, a long way from consideration as a biomarker that will aid in determining whether a stenosing AVG will thrombose after intervention and when to intervene. Nonetheless, like prior observations showing that plasma levels of asymmetric dimethylarginine correlate with the risk for restenosis after angioplasty of AVFs, 20 the study of Wu et al 9 identified a specific uremic toxin linked with a particular postintervention outcome and will likely stimulate the search for others. The fact that certain adverse outcomes but not others associate with indoxyl sulfate suggests that predicting postintervention access outcomes may be better served by a panel of biomarkers rather than a single candidate.…”

mentioning

confidence: 77%

Dialysis Vascular Access Intervention and the Search for Biomarkers

Nath

2016

Journal of the American Society of Nephrology

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much rarer events, such as cancer incidence and progression (or anaphylaxis as the peginesatide example woefully highlights), will remain unaddressed even in such ambitious phase 3 programs and will require additional efforts (and regulator mandates) for top quality and prospective postmarketing surveillance on potential approval. DISCLOSURES C.R.L. has nothing to disclose. In the past year, W.C.W. has served as a scientific advisor to Amgen and Astra-Zeneca and on an event adjudication committee for Medtronic. Hemodialysis vascular accesses are often referred to by any one of a triad of tropes: lifeline because of their indispensability for hemodialysis; Achilles' heel since access complications contribute substantially to the morbidity and mortality in this patient population; and Cinderella as the field of vascular access has never received its merited attention. Understanding the basis for access complications and failure and developing strategies that effectively mitigate both sets of adverse outcomes are necessary objectives in improving the wellbeing of patients maintained on chronic hemodialysis. 1 Of the available vascular accesses, the least desired is the central venous catheter, and the most favored is the arteriovenous fistula (AVF). Even for the AVF, the outcomes are dismal, with 30%-60% of the created AVFs never usable for hemodialysis 2,3 ; recent analyses indicate that the median cumulative patency for AVFs (placed as the first access) is 7.4 months, which increases to 61.9 months when primary AVF failures are excluded. 4 Moreover, a significant subset of functioning AVFs requires endovascular or surgical procedures to achieve and/or maintain such functionality; AVFs that require intervention to achieve maturation have decreased cumulative survival compared with AVFs that successfully mature on their own. 5 Arteriovenous grafts (AVGs) are generally placed when available veins are inadequate for AVFs, and, in a quite limited number of specific settings, there is a gathering sense that an Published online ahead of print. Publication date available at www.jasn.org.

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Plasma ADMA Predicts Restenosis of Arteriovenous Fistula

Cited by 40 publications

References 49 publications

Future research directions to improve fistula maturation and reduce access failure

Future research directions to improve fistula maturation and reduce access failure

Characterization of a Model of an Arteriovenous Fistula in the Rat

Dialysis Vascular Access Intervention and the Search for Biomarkers

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