Local Activation of Interleukin 6 Signaling Is Associated With Arteriovenous Fistula Stenosis in Hemodialysis Patients

Marrone, Daniela; Pertosa, Giovanni; Simone, Simona; Loverre, A.; Capobianco, Carmen; Cifarelli, M. T.; Memoli, Bruno; Schena, Francesco Paolo; Grandaliano, Giuseppe

doi:10.1053/j.ajkd.2007.02.266

Cited by 36 publications

(31 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we report that several inflammatory and oxidative markers associated with IH formation are prevalent in veins used for AVF conduits at the time of AVF creation in CKD patients. This finding complements previous reports that veins at the time of AVF failure also have elevated levels of IL-6, total TGF-β, and HNE (11-13). Based on the presence of inflammatory and oxidative mediators at the time of AVF failure (12,13), inflammation and oxidation have been suggested to predispose the AVF to future failure.…”

Section: Discussionsupporting

confidence: 90%

Inflammation, Oxidation and Venous Neointimal Hyperplasia Precede Vascular Injury from AVF Creation in CKD Patients

et al. 2011

View full text Add to dashboard Cite

Purpose Intimal hyperplasia (IH), a well-recognized cause of dialysis vascular access failure, is generally believed to be an acquired pathologic lesion. Recent data suggests that IH is present prior to AVF creation. We sought to determine whether pre-existing inflammation and oxidation co-exist with IH prior to their incorporation into an AVF conduit, as their presence may predispose the AVF to further IH following AVF creation. Methods At the time of first AV access surgery, vein segments were collected from ten Stage 4 and 5 CKD patients undergoing AVF creation 6-12 months prior to anticipated dialysis initiation. Morphometry and immunohistochemistry was performed to detect inflammatory markers IL-6, TGF-β1, and TNFa, and markers of DNA oxidative damage (8-Hydroxy-2′-deoxyguanosine [HNE]) and lipid peroxidation (4-Hydroxy-2-Nonenal [8OHdG]). Results The degree of IH severity was variable. IL-6, TGF-β1, and TNFa co-localized with a-smooth muscle actin prominently within the venous intima and media. Although more diffuse, HNE and 8OHdG were intensely expressed in parallel with the inflammatory markers. In spite of these findings, however, neither extant IH nor the intensity of inflammatory or oxidative markers were associated with primary or secondary AVF failure at 12 month follow-up. Conclusions Not only does venous IH pre-exist, but inflammation and oxidation markers are present within veins used for the AVF conduit prior to its creation in CKD patients as early as one year before dialysis is commenced. Nevertheless, short and long-term AVF outcomes were not associated with the inflammatory or oxidative burden, suggesting the complexity of AVF dysfunction in humans with CKD.

show abstract

Section: Discussionsupporting

confidence: 90%

Inflammation, Oxidation and Venous Neointimal Hyperplasia Precede Vascular Injury from AVF Creation in CKD Patients

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The IL-6 -634 G allele has been suggested as an aggravating factor in the progression of renal disease [17,19]. Although previous studies have explored the relationship between IL-6 levels and vascular access dysfunction in HD patients [20-22], the effect of IL-6 polymorphisms on vascular access dysfunction has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 -634 C/G and -174 G/C Polymorphisms in Korean Patients Undergoing Hemodialysis

Ryu

Kim

2012

Korean J Intern Med

View full text Add to dashboard Cite

Background/AimsChronic inflammatory status is a possible risk factor for vascular access dysfunction in hemodialysis (HD) patients, but susceptibility differences appear among individuals. Interleukin (IL)-6 is a well-known inflammatory cytokine with various polymorphisms. We examined whether IL-6 polymorphisms are associated with vascular access dysfunction in HD patients.MethodsA total of 80 HD patients (including 42 diabetic patients) were enrolled. Polymorphisms in the IL-6 gene promoter (-634 C/G and -174 G/C) were studied using restriction length polymorphism polymerase chain reaction analysis. Vascular access patency was compared between the patient groups with respect to IL-6 polymorphisms. An additional 89 healthy individuals were enrolled in the control group. Plasma IL-6 levels were de termined by enzyme-linked immunosorbent assay.ResultsThe GG genotype and G allele at position -634 in the IL-6 promoter were more frequently observed in HD patients than in controls. Furthermore, the distribution of the -634 polymorphism differed according to vascular access patency in non-diabetic HD patients. However, the G allele was not a significant risk factor for early access failure. No significant association appeared between the IL-6 -634 C/G polymorphism and plasma IL-6 levels. The C allele of the IL-6 -174 G/C polymorphism was not detected in our study population.ConclusionsThe IL-6 -634 G allele appears with greater frequently in patients with end-stage renal disease and may be associated with vascular access dysfunction in non-diabetic HD patients.

show abstract

“…27–29 Finally, in patients having undergone AVF creation, markers of IL-6 activation were greater in the venous limb of failed AVF versus those that successfully matured. 30 Our work directly links this to adipose tissue and shows that this phenotype exists prior to AVF creation.…”

Section: Discussionmentioning

confidence: 77%

Adipose phenotype predicts early human autogenous arteriovenous hemodialysis remodeling

Mauro

Ding

Hou

et al. 2016

Journal of Vascular Surgery

View full text Add to dashboard Cite

Objective Substantial proportions of autogenous arteriovenous hemodialysis access fistulas (AVF) fail to mature for unclear reasons. AVFs develop in a large mass of surrounding adipose tissue that is increasingly recognized as an active participant in the vascular response to injury via paracrine and endocrine mechanisms. We thus hypothesized that baseline phenotypic characteristics of the adipose juxtaposed to the developing AVF associate with subsequent inward or outward vein wall remodeling. Methods Clinical data and subcutaneous adipose tissue were collected from consented patients undergoing AVF creation (n=22). Tissue was assayed (protein levels) for IL-6, IL-8, leptin, TNF-α, MCP-1, resistin, and adiponectin. Duplex ultrasound vein dimensions were acquired pre-operatively and 4–6 weeks post-operatively at a point 1cm cephalad to the arteriovenous anastomosis (most common location of AVF stenosis). Results The vein at the assayed location outwardly remodeled 55.7% on average (pre-median 3.7 mm, post-median 4.7 mm; p=0.005). Pre-operative vein diameter failed to correlate with post-operative size at the point of assay (R=0.31, p=0.155) unless two outliers were excluded (R=0.64, p=0.002). After removal of the same outliers, the correlation coefficient between venous diameter change (pre-operative vs. post-operative) and IL-8, TNF-α, MCP-1, resistin, and adiponectin was −0.49, −0.79, −0.66, −0.64, and −0.69 respectively (p<0.05). Post-operative AVF flow volume correlated with MCP-1 (−0.53, p<0.05) and adiponectin (−0.47, p<0.05). Conclusion These data reveal a novel relationship between local adipose phenotype and the eventual venous wall response to hemodynamic perturbation in humans. The predictive value of these mediators generally equaled or exceeded that of pre-operative vein size. Beyond providing mechanistic insights into vascular wall adaptations due to flow perturbations, this discovery suggests that strategies focused on altering adipose tissue biology may improve AVF maturation.

show abstract

Local Activation of Interleukin 6 Signaling Is Associated With Arteriovenous Fistula Stenosis in Hemodialysis Patients

Cited by 36 publications

References 32 publications

Inflammation, Oxidation and Venous Neointimal Hyperplasia Precede Vascular Injury from AVF Creation in CKD Patients

Inflammation, Oxidation and Venous Neointimal Hyperplasia Precede Vascular Injury from AVF Creation in CKD Patients

Interleukin-6 -634 C/G and -174 G/C Polymorphisms in Korean Patients Undergoing Hemodialysis

Adipose phenotype predicts early human autogenous arteriovenous hemodialysis remodeling

Contact Info

Product

Resources

About