Arteriovenous Access Thrombosis Research Articles

#532 Association between blood flow measured within 30 days from AV access creation and the risk of thrombosis

Abstract Background and Aims The use of arteriovenous (AV) access for hemodialysis (HD) is hampered by the risk of dysfunction and thrombosis. Various factors affect the risk of AV access thrombosis, such as age, female sex, hematocrit, vessels’ diameter and anatomy, and patients’ comorbidities (e.g. diabetes mellitus, thrombophilia, chronic inflammatory disease). Previous studies have reported contradictory results on the prognostic value of intraoperative blood flow (Qa) measurements. Finally, only few studies have investigated the association between postoperative Qa measurements and thrombosis risk. Therefore, current guidelines report that there is not enough evidence to suggest routine assessment of AV access Qa for surveillance. This study aimed to analyze the association between Qa, measured at the first post-operative visit (within 30 days from creation), and thrombosis risk, in distal and proximal autologous AV fistulae (dAVF and pAVF), and AV grafts (AVG). Method This retrospective cohort study included all AV accesses created in San Paolo Hospital (Milan, IT) between January 1st 2013 and December 31st 2022, with a post-operative Qa measurement available within 30 days from the date of creation. AV accesses were classified as dAVF, pAVF and AVG. Qa was measured by ultrasound as the product of the cross-sectional area and the time-averaged mean velocity, in the feeding artery. The thrombosis-free survival of dAVF, pAVF and AVG was plotted using the Kaplan Meier method. The association between Qa and the risk of thrombosis was studied by Cox proportional hazard models, adjusted for patient's age and sex. Non-linearity was assessed using natural splines. Results A total of 218 AV accesses (92 dAVF, 76 pAVF, and 50 AVG) were created in 191 patients. At baseline, patients had a median age of 69 years, 70% were male, 42% were already on HD treatment, and overall, they had a high prevalence of hypertension, diabetes mellitus and cardiovascular comorbidities. At first post-operative visit, median Qa was 922 [698, 1278] ml/min, 1260 [917, 1825] ml/min, and 1665 [1195, 2508] ml/min, respectively for dAVF, pAVF, and AVG (p <0.001). During a median follow up time of 1.35 [0.55, 2.62] years, 66 AV access thrombosis occurred. The thrombosis-free survival rates for dAVF, pAVF and AVG were 84%, 97%, and 51% at 1 year, and 63%, 66%, and 19% at 5 years (Fig. 1). For dAVF we found a significant L-shaped association between Qa measured at the first post-operative visit and thrombosis risk, with the lowest risk found at Qa of 1289 ml/min and an exponential risk increase for dAVF with Qa <800 ml/min (Fig. 2). Particularly, for dAVF with Qa < 1289 ml/min, we found a 39% increased risk of thrombosis for every 100 ml/min decrease in Qa (aHR 1.39, 95% CI 1.10-1.75, p 0.006). In pAVF, Qa showed a trend of inverse linear association with the risk of thrombosis, although not reaching statistical significance (aHR 1.06, 95% CI 0.96-1.17, p 0.24, for every 100 ml/min decrease in Qa). In AVG, Qa was not associated with the risk of thrombosis (aHR 1.01, 95% CI 0.97-1.06, p 0.57, for every 100 ml/min decrease in Qa). Conclusion In our cohort we found that Qa, measured at the first post-operative visit, is associated with the risk of thrombosis in dAVF, but not in pAVF and AVG. In particular, in dAVF the association is non-linear with the lowest risk in our cohort found at Qa equal to 1289 ml/min, with an exponentially increasing risk for Qa <800 ml/min. Our findings suggest that post-operative flow assessment may be a useful tool to identify dAVF at higher risk of thrombosis and allow a closer monitoring or possible preventive interventions.

Efficacy and safety of low dose, weight-based subcutaneous enoxaparin protocol in recurrent arteriovenous access thrombosis.

This study aims to evaluate the safety and efficacy of a short-term, low dose, weight-based subcutaneous enoxaparin protocol (SEP) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis. Prospective follow-up of 25 patients who presented to a tertiary institution with recurrent AV access thrombosis and treated with anticoagulation according to SEP following successful thrombectomy. Patency and safety outcomes of SEP were studied. The participants were 66.4 ± 10.2 years old and predominantly male (60%) and of Chinese ethnicity (72%). The AV accesses had a median age of 1.4 (0.6, 5.6) years with 60% being non-autogenous arteriovenous access while 40% were autogenous arteriovenous access. Thrombolytic agents (urokinase (72%) or alteplase (28%)) were used in all procedures while adjunct thrombectomy device was used in only four procedures. The mean dose of enoxaparin was 36.0 ± 8.2 mg or 0.64 ± 0.1 mg/kg/day for a mean duration 30.0 days (Interquartile range: 27.5, 31.0). One patient developed minor bleeding episode. Kaplan-Meier analysis demonstrated that the mean thrombosis-free survival pre- versus post-SEP adoption was 27.3 (95% CI 17.9-36.7) versus 183.5 (95% CI 100.1-266.9) days (p < 0.001). After adjusting for the type of thrombolytic agent, use of adjunct thrombectomy device, cutting balloon, drug-coated balloon, and stent graft, SEP remained a significant factor associated with longer thrombosis-free patency (HR 0.166: 95% CI 0.070-0.392, p < 0.001). SEP appears to be a feasible and safe thromboprophylaxis method to improve thrombosis-free patency for AV access with recurrent thrombosis.

Thrombectomy approach for access maintenance in the end stage renal disease population: a narrative review.

This article reviews current practices and outcomes in endovascular thrombectomy techniques for the treatment of thrombosed arteriovenous grafts (AVGs) and fistulas (AVFs). Arteriovenous (AV) access allows patients with end-stage renal disease (ESRD) to receive hemodialysis. Thrombosis of AV access can lead to delay in hemodialysis or abandonment of access requiring dialysis catheter placement. Endovascular approach has become the preferred treatment option for thrombosed access over surgery. Interventions include removal of thrombus from the AV circuit and treatment of the underlying anatomical abnormality, such as an anastomotic stenosis. Thrombolysis, or the act of dissolving thrombus, is performed by using infusion catheters or pulse injector devices for the administration of fibrinolytic agents. Thrombectomy, or the mechanical removal of thrombus, is performed by using embolectomy balloon catheters, rotating baskets or wires, rheolytic and aspiration mechanisms. Adjunctive methods such as cutting balloon angioplasty, drug-coated balloon (DCB) angioplasty, and stent placement are also used to treat stenoses in the AV circuit. Complications of these procedures include vessel rupture, arterial embolism, pulmonary embolism (PE), and paradoxical embolism to the brain. This narrative review article was written based on literature search from electronic databases, including PubMed and Google Scholar. The understanding of thrombectomy techniques and their potential complications is essential in the management of patients with thrombosed AV access.

Supplementation with Folic Acid and Cardiovascular Outcomes in End-Stage Kidney Disease: A Multi-Institution Cohort Study.

Background: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD. Methods: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score. Results: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects. Conclusion: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.

Surgical versus endovascular intervention for vascular access thrombosis: a nationwide observational cohort study.

ABSTRACTBackgroundThere is no consensus whether an arteriovenous (AV) access thrombosis is best treated by surgical or endovascular intervention. We compared the influence of surgical versus endovascular intervention for AV access thrombosis on access survival using real-life data from a national access registry.MethodsWe included patients from the Swedish Renal Access Registry (SRR-Access) with a working AV access undergoing surgical or endovascular intervention for their first thrombosis between 2008 and 2020. The primary outcome was the risk of access abandonment (secondary patency at 30, 60, 90 and 365 days). Secondary outcomes were time to next intervention and 30-day mortality. Access characteristics were obtained from the SRR-Access and patient characteristics were collected from the Swedish Renal Registry. Outcomes were assessed with multivariable logistic regression and Cox proportional hazards regression models adjusted for demographics, clinical and access-related variables.ResultsA total of 904 patients with AV access thrombosis (54% arteriovenous fistula, 35% upper arm access) were included, with a mean age of 62 years, 60% were women, 75% had hypertension and 33% had diabetes. Secondary patency was superior after endovascular intervention versus surgical (85% versus 77% at 30 days and 76% versus 69% at 90 days). The adjusted odds of access abandonment within 90 days and 1 year were higher in the surgical thrombectomy group {odds ratio (OR) 1.44 [95% confidence interval (CI) 1.05–1.97] and OR 1.25 (0.94–1.66), respectively}. Results were consistent in the long-term analysis. There was no significant difference in time to next intervention or mortality, and results were consistent within subgroups.ConclusionsEndovascular intervention was associated with a small short- and long-term benefit as compared with open surgery in haemodialysis patients with AV access thrombosis.

Influence of intradialytic systolic blood pressure changes on arteriovenous access thrombosis in maintenance hemodialysis patients.

Arteriovenous access (AV) thrombosis is an important and preventable problem amongst chronic hemodialysis (HD) patients. Systolic blood pressure (SBP) fluctuation relates to higher cardiovascular mortality amongst these patients. We proposed there is a close relation between SBP changes and arteriovenous (AV) access thrombosis. We also determined other risk factors and biochemical parameters related to AV access failure. 50 HD patients with thrombosis and 50 HD patients without thrombosis were included in the study. Odds ratios and 95% confidence intervals were estimated with multivariate-adjusted logistic regression models to determine the association between potential thrombosis-related risk factors and thrombosis risk. Elder adults, women, and patients with AV grafts, lower intradialytic SBP and higher SBP variations during HD sessions had higher incidence of AV access thrombosis. AV access infection and decreased blood flow (BF) velocity were associated with an increased incidence of thrombotic events, whereas the use of anti-thrombotic agents was associated with a decreased incidence of thrombotic events. Further, anaemia, hypoalbuminemia, hyperlipidemia, and impaired mineral metabolism parameters were also found to be associated with AV access thrombosis. Close monitoring and management of intradialytic hypotension and SBP fluctuation in every HD session are important. Some important and novel modifiable risk factors related to AV access thrombosis were identified in this study (eg, AV access infection, decreased BF and abnormal biochemical parameters, etc). Earlier surveillance and modification of these risk factors is crucial to prevent AV access failure in HD patients.

The association of genotype polymorphisms with vascular access patency in hemodialysis patients.

Some hemodialysis patients suffer from repeat dysfunction of dialysis vascular access and need procedures of angioplasty, thrombectomy, and even temporary catheter use. Why these patients are vulnerable to vascular access dysfunction and how to improve its patency are imperative to be discovered. Traditional risk factors for vascular access function had been widely investigated but could not fully explain this question. Several genotype polymorphisms were demonstrated to increase the incidence of cardiovascular disease and might also be linked to higher risk of vascular access dysfunction. As the major causes of arteriovenous access thrombosis are hypercoagulable status and arteriovenous access stenosis, the investigated genes mainly focus on the mediators of the coagulation cascade, inflammatory process, and endothelial dysfunction. The reported polymorphisms of genes significantly associated with arteriovenous access dysfunction included genes encoding methylene tetrahydrofolate reductase, coagulation factors, heme oxygenase-1, matrix metalloproteinase, transforming growth factor-β1, tumor necrosis factor-α, vascular endothelial growth factor-A, renin-angiotensin-aldosterone system, and protein methyl transferase. However, further prospective study is indispensable to elucidate the association between the genotype polymorphisms and the outcome of vascular access. More and more therapeutic options that focus on genotype polymorphisms may generate a great benefit to the patency of vascular access of uremic patients.

Distal Revascularization and Interval Ligation “DRIL” Procedure in Steal Syndrome Management in Hemodialysed Patients

Background: Steal syndrome complicates access in an increasing number of chronic renal failure (CRF) patients. Surgical procedures as (banding or fistula ligation) to manage this issue have proved to be entirely unsatisfactory because of loss of the recently created access through ligation or attempted salvage by increasing resistance within the fistula. Objective: To determine the results of DRIL technique in treating steal syndrome in CRF patients. Methods: A retrospective study (2015 to 2017) was conducted on 49 patients complaining of steal syndrome (out of 1200 CRF patients) with ages ranged from 35 to 71 years (mean=57 years) after obtaining written informed consent. Twenty nine patients were females (59.1%) and 20 (40.9%) were males. These subjects have undergone DRIL procedure in Vascular Surgery Departments, Qena and Assiut University Hospitals. Pre-procedural angiography was performed in most cases. Patient characters, risk factors, types of fistulae and indications for surgery were listed. The clinical outcomes of the procedure, Arteriovenous Access (AVA) and bypass graft patency were determined as well. Results: The AVA, which led to steal syndrome, was proximally located in the arm (brachiocephalic in 14, brachiobasilic in 14, and prosthetic brachio-axillary in the remaining 21 patients). Steal symptoms comprised hand ache, neurologic deficiency and gangrenous ulcerations. The procedure was technically effective in all subjects. Prompt and total pain release was accomplished in 43 (87.7%) of the 49 patients. One patient (2%) with gangrene later underwent transmetacarpal amputation. No patient required hand amputation. During follow-up (range 0.5 ± 17 months) hemodialysis was carried out continuously using the AVA in 40 subjects. AVA thrombosis had happened in 8 (16.3%) subjects only post DRIL. Significant difference was found between diabetes and occurrence of steal syndrome (p value<0.05) and between type of fistula (prosthetic AVF) and steal syndrome as well (p value<0.05). Six subjects died from other causes not related to the performed procedure. Conclusion: In certain subjects DRIL technique is a secure and efficient method to manage steal syndrome. AVA durability is not influenced by this procedure. Pre-operative angiography pre and post AVA manual compression is essential for adequate patients’ selection in which benefit will be gained mostly by the performed procedure.

Sex hormones in women with kidney disease.

Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question.

A meta-analysis of randomized clinical trials assessing hemodialysis access thrombosis based on access flow monitoring: where do we stand?

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommends the routine use of hemodialysis arteriovenous (AV) access surveillance to detect hemodynamically significant stenoses and appropriately correct them to reduce the incidence of thrombosis and to improve accesses patency rates. Access blood flow monitoring is considered as one of the preferred surveillance method for both AV fistulas (AVF) and AV grafts (AVG); however, published studies have reported conflicting results of its utility that led healthcare professionals to doubt the benefits of this surveillance method. We performed a meta-analysis of the published randomized controlled trials (RCTs) of AV access surveillance using access blood flow monitoring. Our hypothesis was that access blood flow monitoring lowers the risk of AV access thrombosis and that the outcome differs between AVF and AVG. The estimated overall pooled risk ratio (RR) of thrombosis was 0.87 (95% confidence interval [CI], 0.67-1.13) favoring access blood flow monitoring. The pooled RR of thrombosis were 0.64 (95% CI, 0.41-1.01) and 1.06 (95% CI, 0.77-1.46) in the subgroups of only AVF and only AVG, respectively. Our results added to the uncertainty of access blood flow monitoring as a surveillance method of hemodialysis accesses.

Arteriovenous Access Monitoring with Ultrasound Dilution in a Pediatric Hemodialysis Unit

Background: Permanent arteriovenous (AV) access is the preferred access for dialysis delivery in children and adolescents requiring chronic hemodialysis (HD). Ultrasound dilution (UD) monitoring of AV access flow is widely used in adult HD units for the early detection of stenosis but experience in pediatrics is limited. Methods: We monitored all maintenance HD patients with AV access using a noninvasive screening algorithm based on UD access flow. We assessed the effectiveness of this algorithm by comparing it to fistulagrams and its impact on AV access-related morbidity. Results: AV access thrombosis rates fell from 13.5 per 100 patient-months on HD during the baseline period to 3.5 per 100 patient-months on HD during the screening period (p < 0.04). The mean blood flow rate by UD measurement was lower in AV accesses that went on to thrombose compared to those without thrombosis (1,203 ml/min/1.73 m² vs. 1,683 ml/min/1.73 m², p < 0.001). When compared to fistulagrams, the screening algorithm was 94% sensitive and 77% specific in detecting hemodynamically significant stenosis, with positive and negative predictive values of 83 and 91% respectively. Conclusions: A noninvasive UD screening algorithm of AV access flow is very sensitive in detecting hemodynamically significant stenosis and can decrease AV access thrombosis rates.

The Natural History of Arteriovenous Access and Risk Factors Associated With Access Thrombosis After Successful Kidney Transplantation

IntroductionThe purpose of this study was to determine the natural history of arteriovenous (AV) access after successful kidney transplantation (KT) and to identify the risk factors of spontaneous access closure in kidney transplant recipients. MethodsWe performed a retrospective review of 115 patients who underwent KT with functioning access from June 2010 to July 2012. AV access patency was checked and recorded daily during the hospital stay and at every visit to the outpatient clinic. Patients were divided into 2 groups according to the patency of access, and risk factors of access thrombosis were assessed. Access patency was followed up until patency was lost or the study was closed. ResultsAt the end of follow-up, 18 (15.7%) AV accesses had spontaneously closed. Mean time to closure was 119 ± 163 days, and 12 of 18 were closed within 90 days after KT. AV access spontaneously closed in 8.5% of male patients, compared with 27.3% of female patients (P = .007), 12.2% of cases with native access compared with 35.3% of cases with artificial access (P = .016), and 11.3% of cases with wrist access compared with 25.7% of cases with elbow access (P = .049). Spontaneously closed AV accesses tended to have a lower mean access flow compared with functioning accesses (P = .019). On multivariate analysis, female sex and AV access flow volume affected spontaneous AV access closure (odds ratio 4.749, 95% confidence interval 1.919–35.383, P = .008; odds ratio 0.998, 95% confidence interval 0.996–0.999, P = .010, respectively). ConclusionsOur results suggest that AV access thrombosis occurs more frequently during the early postoperative period, particularly in female patients or patients with low flow access, whereas it is a rare event in male patients or patients with high access flow, especially in the late postoperative period.

Massively Calcified Intravascular Cast after Removal of a Tunneled Central Vein Catheter for Hemodialysis

Vascular calcifications usually affect the arteries, while central vein calcifications are rare. A 45-year-old hemodialysis patient underwent a chest CT scan before central vein catheterization required for arteriovenous access thrombosis, in July 2011. He was on hemodialysis since 1995 and from 2005 on warfarin treatment because of repeated thrombosis and dysfunction of arteriovenous fistula and central vein catheters (CVC). A previous tunneled CVC placed in the left external jugular vein was removed in December 2010. Eight months later a chest CT scan showed a 79-mm irregular, linear, tubular radiopaque density in the superior vena cava and left brachiocephalic vein. The possibility of a retained catheter fragment was considered, but the final diagnosis was: calcified "cast" adherent to the vessel wall. This is the first report of an intravenous calcified "cast" (originating from peri-catheter calcification) retained after removal of a tunneled dialysis CVC. This finding is significant because it mimics a retained catheter fragment possibly leading to misdiagnosis and exposing patients to additional risk for unnecessary retrieving interventions. Catheter removal or over the wire substitution in the presence of a calcified cast could also be considered a risky procedure. Retained calcified cast should be included among the long-term complications of hemodialysis CVCs. At the time of publication, the patient is alive without any complication related to the pathology reported.

Association of Low Serum Fetuin A Levels With Poor Arteriovenous Access Patency in Patients Undergoing Maintenance Hemodialysis

Fetuin A, a predictor of mortality in dialysis patients, is associated with vascular calcification and atherosclerosis in hemodialysis (HD) patients. Whether it predicts arteriovenous (AV) access patency is unknown. This study aimed to investigate the association between fetuin A and AV access patency in HD patients. Prospective observational study. 238 prevalent HD patients (127 women and 111 men; mean age, 60 ± 12 years) were followed up for AV access patency for 32 months. Tertiles of baseline circulating fetuin A levels, corresponding to 0.15-0.25, 0.26-0.32, and 0.33-0.51 g/L. The major outcome was loss of unassisted AV access patency, defined as AV access thrombosis or need for intervention. Fetuin A and other markers of inflammation. 100 patients had loss of AV access patency (42%) on follow-up. Patients in the lowest fetuin A tertile had the worst AV access patency (log-rank test, χ(2) = 8.68; P = 0.01). Using Cox proportional hazards regression with patients in the lowest fetuin A tertile as reference, patients in the intermediate tertile had an HR of 0.49 (95% CI, 0.29-0.82), whereas those in the highest fetuin A tertile had an HR of 0.43 (95% CI, 0.25-0.75) for loss of AV access patency. Similarly, considering patients using AV fistulas or grafts separately, patients in the highest fetuin A tertile had less risk of losing AV access patency than patients in the other tertiles (HR, 0.40 [95% CI, 0.19-0.84] for patients with AV fistulas and HR, 0.25 [95% CI, 0.10-0.65] for patients with AV grafts). Focus on the patency of prevalent rather than new AV access in maintenance hemodialysis patients. Fetuin A deficiency is associated with a higher risk of loss of AV access patency in either native AV fistulas or AV grafts in HD patients.

Análisis crítico de un artículo: ¿Sirve reducir los niveles de homocisteinemia en los pacientes con insuficiencia renal avanzada?

Context: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. Objective: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Design, Setting and Participant: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance 15 micromol/L). Intervention: Participants received a daily capsule containing 40 mg off olic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. Main outcome measures: The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of allow part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Results: Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < 001) in the vitamin group and 0.4 micromol/L (1.7%; P=.14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs. 436placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 Mis in the vitamin group vs. 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs. 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs. 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = . 38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. Conclusion: Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. Trial registration: clinical trials.gov Identifier: NCT00032435.

Surveillance of arteriovenous hemodialysis access: A systematic review and meta-analysis

Hemodialysis centers regularly survey arteriovenous (AV) accesses for signs of dysfunction. In this review, we synthesize the available evidence to determine to what extent proactive vascular access monitoring affects the incidence of AV access thrombosis and abandonment compared with clinical monitoring. We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and SCOPUS) and sought references from experts, bibliographies of included trials, and articles that cited included studies. Two reviewers independently assessed trial quality and extracted data. We used random effects meta-analysis to estimate the pooled relative risk (RR) and 95% confidence interval (CI) across studies and conducted subgroup analyses to explain heterogeneity. The I(2) statistic was used to assess heterogeneity of treatment effect among trials. Nine studies (1363 patients) compared a strategy of surveillance vs clinical monitoring. A vascular intervention to maintain or restore patency was provided to both groups if needed. Surveillance followed by intervention led to a nonsignificant reduction of the risk of access thrombosis (RR, 0.82; 95% CI, 0.58-1.16; I(2) = 37%) and access abandonment (RR, 0.80; 95% CI, 0.51-1.25; I(2) = 60%). Three studies (207 patients) compared the effect of vascular interventions vs observation in patients with abnormal surveillance result. Vascular interventions after an abnormal AV access surveillance led to a significant reduction of the risk of access thrombosis (RR, 0.53; 95% CI, 0.36-0.76) and a nonsignificant reduction of the risk of access abandonment (RR, 0.76; 95% CI, 0.43-1.37). Very low quality evidence yielding imprecise results suggests a potentially beneficial effect of AV access surveillance followed by interventions to restore patency. This inference, however, is weak and will require randomized trials of AV access surveillance vs clinical monitoring for rejection or confirmation.

Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease

High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L). Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. clinicaltrials.gov Identifier: NCT00032435.

Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis

Recombinant human erythropoietin is commonly used for treatment of anaemia. Our aim was to determine whether targeting different haemoglobin concentrations with such treatment is associated with altered all-cause mortality and cardiovascular events in patients with anaemia caused by chronic kidney disease. We did a meta-analysis of randomised controlled clinical trials that were identified in medical databases and trial registration websites. Trials were eligible for inclusion if they assessed the effects of targeting different haemoglobin concentrations in patients with anaemia caused by chronic disease who were randomly assigned to treatment with recombinant human erythropoietin, recruited at least 100 patients, and had a minimum follow-up of 12 weeks. We analysed nine randomised controlled trials that enrolled 5143 patients. There was a significantly higher risk of all-cause mortality (risk ratio 1.17, 95% CI 1.01-1.35; p=0.031) and arteriovenous access thrombosis (1.34, 1.16-1.54; p=0.0001) in the higher haemoglobin target group than in the lower haemoglobin target group in the fixed effects model without heterogeneity between studies. There was a significantly higher risk of poorly controlled blood pressure (1.27, 1.08-1.50; p=0.004) in the higher haemoglobin target group than in the lower target haemoglobin group with the fixed effects model; however, this was not significant in the random effects model (1.31, 0.97-1.78; p=0.075). The incidence of myocardial infarction was much the same in the two groups. To target higher haemoglobin concentrations when treating patients with anaemia caused by chronic kidney disease with recombinant human erythropoietin puts such patients at increased risk of death. Current guidelines do not include an upper limit for the target haemoglobin concentration; such an upper limit should be considered in future recommendations.

Management of thrombosed dialysis access: thrombectomy versus thrombolysis

More than 250,000 patients per year with end stage renal disease are maintained on long-term hemodialysis. Because of this large population, hemodialysis access procedures now account for a large percentage of operative interventions in the United States. Prosthetic arteriovenous access thrombosis is a frequent complication that occurs at a rate of 0.5 to 0.8 episodes per year and is a major source of hospital admissions, increasing hospital costs, patient morbidity, and physician frustration. Thrombosed grafts often require rescue procedures to extend the life of the graft and make the most use of the limited available access sites. Such salvage procedures of thrombosed prosthetic dialysis shunts may be performed with either conventional surgical or endovascular techniques. Many techniques for declotting have been used, including open surgical thrombectomy, percutaneous pharmacologic or mechanical thrombectomy, and pharmacomechanical techniques. Despite the various treatment options, no individual declotting modality has proven itself superior. Long-term patencies after a single revascularization procedure are meager, with a median of less than 90 days. This article will review prosthetic hemodialysis access graft declotting mechanisms and supporting literature.

Intravenous Streptokinase for Thrombolysis of Occluded Arteriovenous Access

Thrombosis of arteriovenous access is a major cause of morbidity in the patient population undergoing hemodialysis. This investigation utilized the technique of infusing streptokinase directly into the afferent limb of an occluded graft or fistula to restore patency. A total of seven patients was studied, one patient on two separate occasions nine months apart. Total clot lysis was observed in five of eight infusions. Partial clot lysis was seen in two of eight infusions, although one of these patients required thrombectomy to ensure persistent functioning of the fistula. One of the eight episodes was unsuccessful. A postinfusion fistulogram was performed on seven of eight occasions and demonstrated partial clot lysis in two patients or a stenotic lesion requiring surgical revision in two other cases. In conclusion, streptokinase infusion into the thrombosed vascular access appears to be a safe and efficacious technique for this patient population.