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Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation.

ABSTRACT: Introduction:Local inflammation is an important regulator of vascular remodeling. We hypothesized that adipose tissue adjacent to hemodialysis arteriovenous fistulae modulates maturation. Methods:During fistula creation, perivenous adipose was collected from 111 participants in the Hemodialysis Fistula Maturation Study. Nine adipose-associated mediators were measured. Duplex ultrasound was performed at 4 time points postoperatively from 1 day to first cannulation (10-26 weeks). Associations between logarithmically transformed biomarker levels and fistula remodeling were evaluated using mixed effects regression. Results:Elevated interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 were associated with a reduction in the fractional vein diameter during the early time frame of 1 day to 2 weeks (diameter change of 26.6% and 20.4% at the 25th and 75th percentile for IL-6, P = 0.01; 27.8% and 21.1% at the 25th and 75th percentile for MCP-1, P = 0.02), but not in later stages of remodeling. Local leptin levels showed a significant negative correlation with fractional venous flow increase between 2 and 6 weeks (percent flow change 31.4% and 11.3% at the 25th and 75th percentile for leptin, P = 0.03). Conclusion:Thus, impaired fistula vein dilation and reduced capacity for flow augmentation associate with specific local adipose phenotypic signatures in a time-dependent manner. In view of adipose tissue plasticity, these findings raise the possibility of novel adipose-based strategies to facilitate fistula maturation.

SUBMITTER: Sharma G

PROVIDER: S-EPMC6035127 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation.

Sharma Gaurav G Kuppler Christopher C He Yong Y Tao Ming M Ding Kui K Longchamp Alban A Dember Laura M LM Ozaki C Keith CK Berceli Scott A SA

Kidney international reports 20180302 4

<h4>Introduction</h4>Local inflammation is an important regulator of vascular remodeling. We hypothesized that adipose tissue adjacent to hemodialysis arteriovenous fistulae modulates maturation.<h4>Methods</h4>During fistula creation, perivenous adipose was collected from 111 participants in the Hemodialysis Fistula Maturation Study. Nine adipose-associated mediators were measured. Duplex ultrasound was performed at 4 time points postoperatively from 1 day to first cannulation (10-26 weeks). As ...[more]

PMID: 29988980

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Project description:BACKGROUND:An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis. Unfortunately, approximately one-third of fistulae fail at an early stage. Different anaesthetic techniques can influence factors associated with fistula success, such as intraoperative blood flow and venous diameter. A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone. This, however, has not yet been shown in a large trial to influence long-term fistula patency, the ultimate clinical measure of success.The aim of this study is to compare whether a regional anaesthetic block, compared to local anaesthetic infiltration, can improve long-term fistula patency. METHODS:This study is an observer-blinded, randomised controlled trial. Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet, and consent will be obtained in keeping with the Declaration of Helsinki. Patients will be randomised to receive either: (i) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine, or (ii) local anaesthetic infiltration with lignocaine and levobupivicaine.A total of 126 patients will be recruited. The primary outcome is fistula primary patency at three months. Secondary outcomes include primary patency at 1 and 12 months, secondary patency and fistula flow at 1, 3 and 12 months, flow on first haemodialysis, procedural pain, patient satisfaction, change in cephalic vein diameter pre- and post-anaesthetic, change in radial or brachial artery flow pre- and post-anaesthetic, alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound, and fistula infection requiring antibiotics. CONCLUSIONS:No large randomised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae. If the performance of brachial plexus block increases fistulae patency, this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase, and the number of "redo" or revision procedures should be reduced. TRIAL REGISTRATION:This study has been approved by the West of Scotland Research Ethics Committee 5 (reference no. 12/WS/0199) and is registered with the ClinicalTrials.gov database (reference no. NCT01706354).

Project description:End-stage kidney disease, the most advanced stage of chronic kidney disease (CKD), requires renal replacement therapy or kidney transplant to sustain life. To accomplish durable dialysis access, the creation of an arteriovenous fistula (AVF) has emerged as a preferred approach. Unfortunately, a significant proportion of patients that receive an AVF experience some form of hand dysfunction; however, the mechanisms underlying these side effects are not understood. In this study, we used nuclear magnetic resonance spectroscopy to investigate the muscle metabolome following iliac AVF placement in mice with CKD. To induce CKD, C57BL6J mice were fed an adenine-supplemented diet for 3 wk and then randomized to receive AVF or sham surgery. Two weeks following surgery, the quadriceps muscles were rapidly dissected and snap frozen for metabolite extraction and subsequent nuclear magnetic resonance analysis. Principal component analysis demonstrated clear separation between groups, confirming a unique metabolome in mice that received an AVF. AVF creation resulted in reduced levels of creatine, ATP, and AMP as well as increased levels of IMP and several tricarboxylic acid cycle metabolites suggesting profound energetic stress. Pearson correlation and multiple linear regression analyses identified several metabolites that were strongly linked to measures of limb function (grip strength, gait speed, and mitochondrial respiration). In summary, AVF creation generates a unique metabolome profile in the distal skeletal muscle indicative of an energetic crisis and myosteatosis.NEW & NOTEWORTHY Creation of an arteriovenous fistula (AVF) is the preferred approach for dialysis access, but some patients experience hand dysfunction after AVF creation. In this study, we provide a detailed metabolomic analysis of the limb muscle in a murine model of AVF. AVF creation resulted in metabolite changes associated with an energetic crisis and myosteatosis that associated with limb function.

Project description:Hand dysfunction is a common observation after arteriovenous fistula (AVF) creation for hemodialysis access and has a variable clinical phenotype; however, the underlying mechanism responsible is unclear. Grip strength changes are a common metric used to assess AVF-associated hand disability but has previously been found to poorly correlate with the hemodynamic perturbations post-AVF placement implicating other tissue-level factors as drivers of hand outcomes. In this study, we sought to test if expression of a mitochondrial targeted catalase (mCAT) in skeletal muscle could reduce AVF-related limb dysfunction in mice with chronic kidney disease (CKD). Male and female C57BL/6J mice were fed an adenine-supplemented diet to induce CKD prior to placement of an AVF in the iliac vascular bundle. Adeno-associated virus was used to drive expression of either a green fluorescent protein (control) or mCAT using the muscle-specific human skeletal actin (HSA) gene promoter prior to AVF creation. As expected, the muscle-specific AAV-HSA-mCAT treatment did not impact blood urea nitrogen levels (P = 0.72), body weight (P = 0.84), or central hemodynamics including infrarenal aorta and inferior vena cava diameters (P > 0.18) or velocities (P > 0.38). Hindlimb perfusion recovery and muscle capillary densities were also unaffected by AAV-HSA-mCAT treatment. In contrast to muscle mass and myofiber size which were not different between groups, both absolute and specific muscle contractile forces measured via a nerve-mediated in-situ preparation were significantly greater in AAV-HSA-mCAT treated mice (P = 0.0012 and P = 0.0002). Morphological analysis of the post-synaptic neuromuscular junction uncovered greater acetylcholine receptor cluster areas (P = 0.0094) and lower fragmentation (P = 0.0010) in AAV-HSA-mCAT treated mice. Muscle mitochondrial oxidative phosphorylation was not different between groups, but AAV-HSA-mCAT treated mice had lower succinate-fueled mitochondrial hydrogen peroxide emission compared to AAV-HSA-GFP mice (P < 0.001). In summary, muscle-specific scavenging of mitochondrial hydrogen peroxide significantly improves neuromotor function in mice with CKD following AVF creation.

Project description:To assess the anatomic development of native arteriovenous fistula (AVF) during the first 6 weeks after creation by using ultrasonographic (US) measurements in a multicenter hemodialysis fistula maturation study.Each institutional review board approved the prospective study protocol, and written informed consent was obtained. Six hundred and two participants (180 women and 422 men, 459 with upper-arm AVF and 143 with forearm AVF) from seven clinical centers underwent preoperative artery and vein US mapping. AVF draining vein diameter and blood flow rate were assessed postoperatively after 1 day, 2 weeks, and 6 weeks. Relationships among US measurements were summarized after using multiple imputation for missing measurements.In 55% of forearm AVFs (68 of 124) and 83% of upper-arm AVFs (341 of 411) in surviving patients without thrombosis or AVF intervention prior to 6 weeks, at least 50% of their 6-week blood flow rate measurement was achieved at 1 day. Among surviving patients without thrombosis or AVF intervention prior to week 2, 70% with upper-arm AVFs (302 of 433) and 77% with forearm AVFs (99 of 128) maintained at least 85% of their week 2 flow rate at week 6. Mean AVF diameters of at least 0.40 cm were seen in 85% (389 of 459), 91% (419 of 459), and 87% (401 of 459) of upper-arm AVFs and in 40% (58 of 143), 73% (104 of 143), and 77% (110 of 143) of forearm AVFs at 1 day, 2 weeks, and 6 weeks, respectively. One-day and 2-week AVF flow rates and diameters were used to predict 6-week levels, with 2-week prediction of 6-week measures more accurate than those of 1 day (flow rates, R(2) = 0.47 and 0.61, respectively; diameters, R(2) = 0.49 and 0.82, respectively).AVF blood flow rate at 1 day is usually more than 50% of the 6-week blood flow rate. Two-week measurements are more predictive of 6-week diameter and blood flow than those of 1 day. US measurements at 2 weeks may be of value in the early identification of fistulas that are unlikely to develop optimally.

Project description:An endovascular arteriovenous fistula is a recent technological advancement in hemodialysis vascular access. This systematic review and meta-analysis aimed to investigate the efficacy and safety of endovascular arteriovenous fistula (eAVF) creation compared with surgical arteriovenous fistula (sAVF) creation among patients with chronic kidney disease. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Clinical Trials.gov, and the WHO International Clinical Trials Registry Platform until May 2021 to perform meta-analyses using random-effects models. Pre-specified primary outcomes were fistula maturation, procedure-related complications, and patient satisfaction. Secondary outcomes were procedural technical success, procedure time, all adverse events, and medical expenditure. The risk of bias in non-randomized studies of the interventions assessment tool, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach were used to assess the quality of individual studies and the body of evidence, respectively. In seven studies including 860 patients, endovascular arteriovenous fistula creation had little to no effect on fistula maturation (odds ratio, 0.58; 95% confidence intervals, 0.05 to 6.91). Meta-analysis could not be performed for procedure-related complications and patient satisfaction due to insufficient data. For secondary outcomes, endovascular arteriovenous fistula resulted in a slight to no difference in procedural technical success (odds ratio, 0.69: 95% confidence intervals, 0.04 to 11.98) and all adverse events (odds ratio, 6.31; 95% confidence intervals, 0.64 to 62.22). Endovascular fistula creation incurred less medical expenditure than sAVF (mean difference, USD 12760; 95% confidence intervals, -19710 to -5820). Meta-analysis for procedure time was not performed because one of the studies had a critical risk of bias. All of these outcomes were of low certainty of evidence or very low certainty of evidence. There was limited evidence for supporting endovascular arteriovenous fistula creation over conventional surgical arteriovenous fistula creation for patients with chronic kidney disease. Multicenter randomized controlled trials are needed to confirm the efficacy and safety of eAVFs in selected populations.

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Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation.

Publications

Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation.

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