Maintenance of Hemodialysis Vascular Access and Prevention of Access Dysfunction: A Review.

BACKGROUND: Current Renal Association guidelines recommend the creation of an arteriovenous fistula as the first choice for hemodialysis access, with artificial grafts kept in reserve. However, maintaining working access comes with significant difficulties, as well as an estimated annual cost to the National Health Service of greater than £84 million. Multiple methods of improving the successful creation of hemodialysis access, improving access maintenance and preventing access dysfunction therefore exist. The aim was to review these methods, including surgical, radiological, and pharmacological techniques. METHODS: The literature was reviewed up to March 2016 for reports of surgical, radiological, and pharmacology approaches to improve maturation, maintain function, and prevent dysfunction of arteriovenous fistulas and artificial access grafts. RESULTS: Access function has been related to fistula and graft configuration and anastomotic technique. Novel surgical approaches include the use of early-cannulation grafts and biological grafts. Preoperative radiological vessel mapping and access surveillance have both been studied, and once stenosis or thrombosis has occurred, endovascular management techniques for thrombolysis and thrombectomy, along with angioplasty and stenting, are common. Pharmacological trials include the use of antiplatelets, ACE inhibitors, statins, along with perivascular therapies, and other more novel drug targets. CONCLUSIONS: The evidence for the strategies that can be used to maintain access function is highly variable, with many small, observational, and retrospective studies. In the future, the more widespread use of early cannulation grafts, hybrid surgical and endovascular procedures, and the further pursuit of both biological grafts and biological perivascular therapies may yield improvements in vascular access function.

Intravascular brachytherapy for peripheral vascular disease.

BACKGROUND: Interventional treatment of arteries that are narrowed and obstructed by atherosclerosis involves either bypassing the blockage using a graft; widening the artery from the inside with a balloon, a procedure known as percutaneous transluminal angioplasty (PTA); or providing a strut to hold the vessel open, known as a stent. All of these treatments are, however, limited by the high numbers that fail within a year. Intravascular brachytherapy is the application of radiation directly to the site of vessel narrowing. It is known to inhibit the processes that lead to restenosis (narrowing) of vessels and grafts after treatment. This is an update of a review first published in 2002. OBJECTIVES: To assess the efficacy of, and complications associated with, intravascular brachytherapy (IVBT) for maintaining patency after angioplasty or stent insertion in native vessels or bypass grafts of the iliac or infrainguinal arteries. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched their Specialised Register (last searched August 2013) and CENTRAL (2013, Issue 7). SELECTION CRITERIA: Randomised controlled trials of the use of brachytherapy as an adjunct to the endovascular treatment of people with peripheral arterial disease (PAD) or stenosed bypass grafts of the iliac or infrainguinal arteries versus the procedure without brachytherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and two other review authors independently extracted the data. Adverse event information was collected from the trials. MAIN RESULTS: Eight trials with a combined total of 1090 participants were included in this review. All included studies used the femoropopliteal artery. We did not identify any studies that used the iliac arteries. All studies compared PTA with or without stenting plus IVBT versus PTA with or without stenting alone. No trials were found comparing IVBT to technologies such as drug eluting stents or balloons, or cryoplasty. Follow-up ranged from six months to five years. The quality of the included trials was moderate with our concerns relating to the difficulty of blinding due to the nature of the procedures and the small sample sizes for some studies. Primary outcomes (patency or restenosis and need for re-intervention) were reported in the majority of the trials, but reporting at various time points and the use of multiple definitions of the outcomes by the included studies meant that not all data were available for pooling. The secondary outcomes were not reported in many of the included studies.For brachytherapy, cumulative patency was higher at 24 months (odds ratio (OR) 2.36, 95% confidence interval (CI) 1.36 to 4.10, n = 222, P = 0.002). A statistically significant difference was found for restenosis at six months (OR 0.27, 95% CI 0.11 to 0.66, n = 562, P = 0.004), 12 months (OR 0.44, 95% CI 0.28 to 0.68, n = 375, P = 0.0002) and 24 months (OR 0.41, 95% CI 0.21 to 0.78, n = 164, P = 0.007) in favour of IVBT. No difference was found after five years as measured in one study. The need for re-interventions was reported in six studies. Target lesion revascularisation was significantly reduced in trial participants treated with IVBT compared with angioplasty alone (OR 0.51, 95% CI 0.27 to 0.97, P = 0.04) at six months after the interventions. No statistically significant difference was found between the procedures on the need for re-intervention at 12 and 24 months after the procedures.A statistically significant lower number of occlusions was found in the control group at more than three months (OR 11.46, 95% CI 1.44 to 90.96, n = 363, P = 0.02) but no differences were found at less than one month nor at 12 months after the procedures making the clinical significance uncertain. Ankle brachial index was statistically significantly better for IVBT at the 12 month follow-up (mean difference 0.08, 95% CI 0.02 to 0.14, n = 100, P = 0.02) but no statistically significant differences were found at 24 hours and at six months.Quality of life, complications, limb loss, cardiovascular deaths, death from all causes, pain free walking distance and maximum walking distance on a treadmill were similar for the two arms of the trials with no statistically significant difference found between the treatment groups. AUTHORS' CONCLUSIONS: The evidence for using peripheral artery brachytherapy as an adjunct to percutaneous transluminal angioplasty to maintain patency and for the prevention of restenosis in people with peripheral vascular disease is limited, mainly due to the inconsistency of assessment and reporting of clinically relevant outcomes. More data are needed on clinically relevant outcomes such as health related quality of life (HRQOL) or limb salvage and longer-term outcomes, together with comparisons with other techniques such as drug eluting balloons and stents. Adequately powered randomised controlled trials, health economics and cost-effectiveness data are required before the procedure could be recommended for widespread use.

Homocysteine lowering interventions for peripheral arterial disease and bypass grafts.

BACKGROUND: Elevated plasma levels of the amino acid homocysteine (hyperhomocysteinaemia) are associated with narrowing or blocking of the arteries (atherosclerosis). Treatment to lower homocysteine levels has been shown to be both effective and cheap in healthy volunteers. However, the impact of reducing homocysteine levels on the progression of atherosclerosis and patency of the vessels after treatment for atherosclerosis is still unknown and forms the basis for this review. This is the second update of a review first published in 2002. OBJECTIVES: To assess the effects of plasma homocysteine lowering therapy on the clinical progression of disease in people with peripheral arterial disease (PAD) and hyperhomocysteinaemia including, as a subset, those who have undergone surgical or radiological intervention. SEARCH METHODS: For this update, the Cochrane Peripheral Vascular Disease Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Trial databases were searched by the TSC (January 2013) for details of ongoing and unpublished studies. We also searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised trials in which participants with PAD and hyperhomocysteinaemia were allocated to either homocysteine lowering therapy or no treatment, including participants before and after surgical or radiological interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. Information on adverse events was collected from the trials. MAIN RESULTS: Two randomised trials with a total of 161 participants were included in this review. The studies did not report on mortality and rate of limb loss. One randomised trial with a total of 133 participants showed that there was a significant improvement in ankle brachial index (ABI) in participants who received folic acid compared with placebo (mean difference (MD) 0.07, 95% confidence interval (CI) 0.04 to 0.11, P < 0.001) and in participants who received 5-methyltetrahydrofolate (5-MTHF) versus placebo (MD 0.05, 95% CI 0.01 to 0.10, P = 0.009). A second trial with a total of 18 participants showed that there was no difference (P non-significant) in ABI in participants who received a multivitamin B supplement (mean ± SEM: 0.7 ± 01) compared with placebo (mean ± SEM: 0.8 ± 0.1). No major events were reported. AUTHORS' CONCLUSIONS: Currently, no recommendation can be made regarding the value of treatment of hyperhomocysteinaemia in peripheral arterial disease. Further, well constructed trials are urgently required.

Elevated plasma homocysteine is associated with increased brain atrophy rates in older subjects with mild hypertension.

We determined using serial MR imaging whether raised plasma homocysteine levels are associated with increased brain atrophy, white matter lesion (WML) progression or incidence of silent brain infarcts (SBIs) in older hypertensive subjects. Brain atrophy rates (0.58 ± 0.48% per year, mean ± SD) were significantly correlated with homocysteine (ß = 0.46, p = 0.001 homocysteine; ß = 0.44, p = 0.007 homocysteine/folate/B12 models) but not with folate or B12 levels. Progression of WML (0.08 ± 0.16%) was not associated with homocysteine level (B = 0.01, p = 0.29). New SBIs were uncommon. In older hypertensive individuals, plasma homocysteine levels are associated with increased rates of whole-brain atrophy but not WML progression.

Plasma homocysteine and cognitive decline in older hypertensive subjects.

BACKGROUND: Elevated plasma homocysteine concentrations have been associated with both cognitive impairment and dementia. However, it is unclear whether some cognitive domains are more affected than others, or if this relationship is independent of B12 and folate levels, which can also affect cognition. We examined the relationship between plasma homocysteine and cognitive decline in an older hypertensive population. METHODS: 182 older people (mean age 80 years) with hypertension and without dementia, were studied at one center participating in the Study on COgnition and Prognosis in the Elderly (SCOPE). Annual cognitive assessments were performed using a computerized assessment battery and executive function tests, over a 3-5 year period (mean 44 months). Individual rates of decline on five cognitive domains were calculated for each patient. End of study plasma homocysteine, folate and B12 concentrations were measured. The relationship between homocysteine levels and cognitive decline was studied using multivariate regression models, and by comparing high versus low homocysteine quartile groups. RESULTS: Higher homocysteine showed an independent association with greater cognitive decline in three domains: speed of cognition (ß = -27.33, p = 0.001), episodic memory (ß = -1.25, p = 0.02) and executive function (ß = -0.05, p = 0.04). The association with executive function was no longer significant after inclusion of folate in the regression model (ß = -0.032, p = 0.22). Change in working memory and attention were not associated with plasma homocysteine, folate or B12. High homocysteine was associated with greater decline with a Cohen's d effect size of approximately 0.7 compared to low homocysteine. CONCLUSIONS: In a population of older hypertensive patients, higher plasma homocysteine was associated with cognitive decline.

Trends in varicose vein therapy in England: radical changes in the last decade.

INTRODUCTION: We aimed to analyse national trends in varicose vein treatment in the UK National Health Service (NHS). SUBJECTS AND METHODS: The National Hospital Episode Statistics website (www.Hesonline.nhs.uk) was interrogated for patients treated (1998-2008) in the NHS for varicose veins. RESULTS: There has been a 34% decline in patients presenting for an intervention for varicose veins. For surgical procedures alone, the waiting times have fallen by 59%. In 2007-2008, 30,663 (72%) fewer bed days were used in comparison to 1998; accompanied by a 49% decline in the number of patients undergoing surgery. After a 47% decrease between 1998 and 2001, the number of patients requesting sclerotherapy treatment has increased by a substantial 311% over the subsequent 7 years. Transluminal procedures were used almost twice as often in 2007-2008 as in 2006-2007. CONCLUSIONS: There has been a steady decline in the number of patients treated for varicose veins. Fewer patients are undergoing surgery but are being managed more efficiently, with an increase in day cases and a reduction in total bed days. The demand for minimally invasive procedures has increased substantially. These trends will be of great importance for the future planning of vascular surgical services.

Immunotherapy for the prevention of myointimal hyperplasia after experimental balloon injury of the rat carotid artery.

We assessed the effect of novel immunotherapeutic heat-killed bacterial (Actinomycetales) preparations on the development of myointimal hyperplasia (MIH) in a rat carotid balloon trauma model and the effect on the immune response by measuring the expression of interferon gamma (IFN-gamma; (Th1) and interleukin 4 (IL-4; Th2). There was a significant reduction (P < .001) in intima/media ratios (mean +/- SEM) in the rats treated by immunomodulation (0.52 +/- 0.03 Gordonia bronchialis, 0.60 +/- 0.03 Rhodococcus coprophilus, 0.43 +/- 0.03 Tsukamurella inchonensis, 0.37 +/- 0.03 Mycobacterium vaccae), in comparison with untreated controls (0.91 +/- 0.05). Postballoon trauma G bronchialis increased messenger RNA (mRNA) IFN-gamma (P < .02) and reduced mRNA IL-4 (P < .05). R coprophilus, T inchonensis, and M vaccae significantly increased production of mRNA IFN-gamma (P < .001). R coprophilus and M vaccae also decreased production of mRNA IL-4 (P < .05, P < .01). Treatment with heat-killed Actinomycetales inhibits MIH through a combination of enhanced Th1 and attenuated Th2 response. Immunomodulation may provide a novel therapeutic option to prevent restenosis.

The use of an in vivo model to study the effects of hyperhomocysteinaemia on vascular function.

BACKGROUND/AIMS: To use an in vivo rat model of hyperhomocysteinaemia (HHCy) to study its impact on vascular function. METHODS: Twenty rats were fed either a control or HHCy-inducing diet for 10 wk. The response of aortic rings to contraction with phenylephrine, and relaxation to acetylcholine (endothelium-dependant relaxation) or sodium nitroprusside (endothelium-independent relaxation) was analyzed. The results were compared using an analysis of variance (ANOVA). RESULTS: There was a significant elevation of HCy in the treated group (20.5 versus 1.6 micromol/L, P = 0.004). There was no significant difference between the two groups in blood pressure measurements (ANOVA, P = 0.152). In a dose-dependant manner, phenylephrine elicited significantly greater contraction in aorta taken from HHCy rats than that taken from controls (ANOVA, P < 0.001), acetylcholine elicited significantly less percentage relaxation in aorta taken from HHCy rats than from controls (ANOVA, P = 0.003) and though sodium nitroprusside stimulated less percentage relaxation in aorta taken from HHCy rats than controls, this did not reach significance (ANOVA, P = 0.051). CONCLUSIONS: In diet induced hyperhomocysteinaemic rats, there is enhanced vascular contraction in response to phenylephrine and impaired endothelium-dependant relaxation in response to acetylcholine.

Extended storage of whole blood with 3-deazaadenosine for homocysteine assay.

BACKGROUND: To assess the effectiveness of using 3-deazaadenosine (3DAA) to maintain plasma homocysteine concentrations (tHCy) in whole blood samples. METHODS: Blood was obtained from five volunteers and samples were maintained at room temperature, in cold packs or in a fridge (0-4 degrees C) with and without 3DAA. At time points ranging from 6 to 168 h, samples were processed and analysed for tHCy using the Abbott IMx system. RESULTS: There was a mean increase in tHCy of 29.4% at 6 h increasing to 242.6% after 168 h in whole blood kept at room temperature. There was no significant change in tHCy for 48 h when stored in cold packs, and for 72 h when stored in the fridge. The addition of 3DAA had a significant preservative effect (P<0.001), maintaining tHCy to 48 h in whole blood at room temperature, 120 h in the fridge and 96 h in cool packs. There was no statistical difference in results obtained from samples containing preservative and controls when using the Abbott IMx system. CONCLUSION: 3DAA is an effective preservative of tHCy in whole blood, particularly in samples maintained at 0-4 degrees C.