Reprinted article "Factors associated with early failure of arteriovenous fistulae for haemodialysis access".

The radiocephalic arteriovenous fistula remains the method of choice for haemodialysis access. In order to assess their suitability for fistula formation, the radial arteries and cephalic veins were examined preoperatively by ultrasound colour flow scanner in conjunction with a pulse-generated run-off system. Intraoperative blood flow was measured after construction of the fistulae. Post-operative follow-up was performed at various intervals to monitor the development of the fistulae. Radial artery and cephalic vein diameter less than 1.6 mm was associated with early fistula failure. The intraoperative fistula blood flow did not correlate with the outcome of the operation probably due to vessel spasm from manipulation. However, blood flow velocities measured non-invasively 1 day after the operation were significantly lower in fistulae that failed early compared with those that were adequate for haemodialysis. Most of the increase in fistula diameter and blood flow occur within the first 2 weeks of surgery.

Axillary artery aneurysm following closure of haemodialysis fistula. A case report.

Aneurysm formation after ligation of traumatic arteriovenous fistulae is a well-documented event, but this complication has been scarcely reported in vascular access for haemodialysis. We describe a case report of delayed aneurysm formation following closure of a haemodialysis fistula. A 57 year-old man was found to have a left axillary artery aneurysm 10 years after closure of a brachio-cephalic arterio-venous fistula. Though he was initially asymptomatic, 6 years later, he developed a progressive sense of coldness in the left hand and an increase in size of the aneurysm. The patient underwent an uncomplicated reversed saphenous vein bypass to replace the aneurysm. The possible aetiological factors and management options are discussed and pertinent literature reviewed.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts remains unquantified in vivo, but is likely to influence flow patterns and haemodynamics, thereby impacting upon graft patency. This study measured the ratio of distal to proximal outflow in 30 patients undergoing infrainguinal bypass for lower limb ischaemia, using a flow probe and a transit-time ultrasonic flow meter. The mean outflow distribution was approximately 75% distal to 25% proximal, with above knee anastomoses having a greater proportion of distal flow (84%) compared to below knee grafts (73%). These in vivo flow characteristics differ significantly from those used in theoretical models studying flow phenomena (50:50 and/or 100:0), and should be incorporated into future research.

Steal phenomenon in radiocephalic arteriovenous fistula. In vitro haemodynamic and electrical resistance simulation studies.

OBJECTIVE: steal phenomenon following an arteriovenous fistula (AVF) creation is characterised by retrograde flow in the artery segment distal to the anastomosis and occurs in the majority of patients with radiocephalic AVF although this rarely leads to distal ischaemia. To investigate the local haemodynamics after the creation of an AVF, a simple electrical resistance model which assumes time-independent flow was used. The applicability of this model to pulsatile flow conditions was verified using an in vitro flow circuit. The effects of stenoses in various artery segments were also investigated. DESIGN OF THE STUDY: the electrical analogue model consists of a pressure source, constant resistances that represent the resistance to flow of various arterial segments and the fistula. The stenosis was modelled by a resistor and a non-linear term is simulated by a current-controlled voltage source. In vitro experiments were performed in pulsatile and steady flow and the results were compared with electrical simulations. The effects of fistula flow and the presence and severity of a stenosis on flow distribution, particularly the direction of flow in the distal radial artery and flow into the hand were assessed. RESULTS: steady and pulsatile time-averaged flows measured in vitro compared well with the results of electrical circuit simulations for cases without a stenosis. When a stenosis was present comparisons were made only in steady flow and these show good agreement for stenoses of 75% area reduction. The direction of flow in the distal radial artery was antegrade (towards the hand) at low fistula flow and became retrograde as fistula flow increased. The presence of a severe stenosis in the brachial artery was found to have the strongest influence on flow to the hand. CONCLUSIONS: an electrical resistance model of a radiocephalic AVF has been validated with an in vitro pulsatile flow circuit. One of the benefits of this model is that it can be easily analysed using standard circuit simulation software. The model also provide insights into the possible haemodynamics consequences of creating an AVF with or without the presence of a stenosis in the arterial segments.

Muscle oxygenation and ATP turnover when blood flow is impaired by vascular disease.

31P magnetic resonance spectroscopy (31P MRS) and near-infrared spectroscopy (NIRS) are combined to study interactions between oxidative ATP synthesis rate, perturbation of the creatine kinase equilibrium, and cellular oxygenation state in calf muscle of normal subjects and patients with muscle perfusion impaired by peripheral vascular disease.

Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: a combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo.

PURPOSE: We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD). METHODS: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined. RESULTS: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject. CONCLUSION: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.

Association of tumour necrosis factor alpha and interleukin 6 levels with cytomegalovirus DNA detection and disease after renal transplantation.

Cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are thought to be important in the pathogenesis of post-transplant cytomegalovirus (CMV) disease. CMV infection increases the production of TNF-alpha and IL-6. Conversely, TNF-alpha switches on the replication of CMV. To study the association of these two cytokines with CMV activity and disease, TNF-alpha and IL-6 levels were assayed in plasma samples taken serially from three groups of renal transplant recipients. Group A (n = 12) had CMV disease and syndrome; Group B (n = 11) had detectable CMV DNA in plasma or peripheral blood leucocytes without disease, i.e., presumed asymptomatic CMV infection, and Group C (n = 11) had no detectable CMV DNA nor disease. The median peak TNF-alpha levels in patients with CMV disease (Group A) were significantly higher than that in Group B or Group C (P < 0.02) whereas the median peak IL-6 levels in group C patients were significantly lower than that in group A (P < 0.04) or group B (P < 0.03). A TNF-alpha level of above 100 pg/ml was significantly associated with CMV disease and high plasma CMV load (> 10,000 copies/ml). IL-6 levels above 15 pg/ml were significantly associated with CMV DNA detection, but not with CMV disease or elevated CMV load. High levels of TNF-alpha or IL-6 were not associated with CMV donor/recipient serostatus, HHV-6 or HHV-7 DNA detection, immunosuppressive regimen or rejection episodes. The role of TNF-alpha in the pathogenesis of CMV disease deserves further investigation.

Graft distortion after endovascular repair of abdominal aortic aneurysm: association with sac morphology and mid-term complications.

PURPOSE: To investigate the incidence, significance, and mechanism of stent-graft distortion after endovascular repair (EVR) of abdominal aortic aneurysm. METHODS: EVR of abdominal aortic aneurysm was performed in 51 cases (49 modular, bifurcated; 2 tube). Thirty-two patients were followed for 6 or more months and had equivalent baseline and follow-up images which could be used to determine changes in graft configuration. Sac dimensions were measured using computed tomographic (CT) images and graft-related complications were recorded. RESULTS: Amongst 32 patients evaluated on follow-up, there was graft distortion in 24. Distorted grafts were significantly (p = 0.002) associated with sac diameter reduction (mean 5 mm) and sac length reduction (mean 8.1 mm). All graft-related complications occurred in the limbs of eight distorted grafts, with a mean reduction of sac length in this group of 7.8 mm on reformatted CT images. CONCLUSION: There was a highly significant association between graft distortion and limb complications, and reduced sac dimensions.

Association of human herpesvirus 7 with cytomegalovirus disease in renal transplant recipients.

BACKGROUND: Recent studies have linked human herpesviruses 6 (HHV-6) and 7 (HHV-7) with posttransplant cytomegalovirus (CMV) disease. METHODS: Thirty-seven renal transplant recipients were monitored weekly for CMV, HHV-6, and HHV-7 DNA and serological responses for 12 weeks after transplantation. Plasma CMV load and the occurrence of CMV disease was related to HHV-6 and -7 detection. RESULTS: CMV disease was identified in 12 patients. In a logistic regression analysis, factors significantly associated with CMV disease were the detection of HHV-7 DNA in peripheral blood leucocytes and donorrecipient CMV serostatus. Patients with detectable HHV-7 DNA had significantly higher peak plasma CMV loads (P=0.01). CONCLUSIONS: An association was found between HHV-7, but not HHV-6, DNA detection and CMV disease, suggesting a possible role of HHV-7 in its pathogenesis.

Freedom from endoleak after endovascular aneurysm repair does not equal treatment success.

OBJECTIVE: To determine whether freedom from endoleak after endovascular repair of abdominal aortic aneurysm (EVAR) is a reliable guide to freedom from persistent or recurrent pressurisation of the aneurysm sac (endotension) and therefore freedom from risk of rupture. PATIENTS AND METHODS: The records of 55 patients followed for more than 3 months after EVAR were reviewed to correlate the presence or absence of endoleak on contrast-enhanced CT and/or angiography with changes in maximum aneurysm diameter (DMAX). RESULTS: in 22 (40%) patients there was no significant change in DMAX during follow-up. In 21 of these no endoleak was observed on CT or angiography. One patient developed a secondary side-branch endoleak which remains under observation. In 18 (33%) patients, DMAX decreased during follow-up. Thirteen of these remained free of endoleak. Four patients developed secondary endoleaks which were treated by secondary intervention. One patient with persistent primary endoleak suffered fatal aneurysm rupture three days before planned intervention. DMAX increased in 15 (27%) patients. In only five of these could an endoleak be identified on CT and/or angiography. One primary side-branch endoleak persists following failed embolisation. Four secondary endoleaks have been corrected by secondary intervention. Four of the remaining 10 patients died suddenly from unknown cause. All had DMAX greater than 65 mm at last follow-up. One patient underwent late conversion, which suggested continued pressurisation through thrombus at the site of a "sealed" primary proximal endoleak. Two patients are scheduled to undergo embolisation of patent side-branches revealed only by Levovist enhanced Duplex scanning and three patients remain under observation. CONCLUSION: Freedom from endoleak on conventional imaging incorrectly suggested freedom from endotension in 10 (18%) of our patients. Follow-up after endovascular repair must include regular measurement of DMAX and/or aneurysm sac volume to identify those patients who remain at risk of rupture.

Comparison of two commercial methods for measurement of cytomegalovirus load in blood samples after renal transplantation.

A cohort of 77 renal transplant recipients was prospectively studied for comparison of two commercially available cytomegalovirus (CMV) load assays, i.e., the COBAS AMPLICOR CMV Monitor test (Amplicor), using plasma samples, and the Murex Hybrid Capture System (HCS), using whole blood. The manufacturer of the HCS assay changed the version of the test from 1.0 (HCS-1) to 2.0 (HCS-2) after the first 37 patients had been tested. Despite the differences in principle and type of specimen used, the Amplicor and HCS assays gave comparable results. The regression line correlating the HCS-1 assay to the Amplicor assay was similar to that correlating the HCS-2 assay to the Amplicor assay. The HCS results could be converted to Amplicor-equivalent units by using linear-regression equations [log(10) HCS-1 result = 0.49 (log(10) Amplicor result) + 2.58, and log(10) HCS-2 result = 0.61 (log(10) Amplicor result) + 2.18]. The HCS-2 assay appeared to have the lowest detection limit, followed by the Amplicor assay and then the HCS-1 assay. When a sliding scale of cutoff values in Amplicor-equivalent units (>1,000, >2,500, >6,000, >16,000, >40,000, and >100,000 copies/ml) was applied to diagnose CMV disease, similar patterns of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were observed with the Amplicor and HCS assays. A cutoff value of >40,000 copies/ml has a low sensitivity (Amplicor, 29.4%; HCS, 41.2%) but is specific (Amplicor, 96.7%; HCS, 93.3%) and can be used for the differential diagnosis of CMV disease (PPV, 71.4% [Amplicor] or 63. 6% [HCS]; NPV, 82.9% [Amplicor] or 84.8% [HCS]). A lower cutoff value of >1,000 copies/ml improves the sensitivity (Amplicor, 76.5%; HCS, 82.4%) and has a high NPV (Amplicor, 91.8%; HCS, 94.2%) but, due to the low PPV (Amplicor, 46.2%; HCS, 56%), is useful only for exclusion of CMV disease.

Prediction and diagnosis of cytomegalovirus disease in renal transplant recipients using qualitative and quantitative polymerase chain reaction.

BACKGROUND: Preemptive antiviral therapy against cytomegalovirus (CMV) disease after transplantation requires information from suitable laboratory markers. We examined the use of qualitative and quantitative polymerase chain reaction (PCR) to monitor renal transplant recipients. METHODS: A cohort of 77 renal transplant recipients was monitored using an in-house and a commercial (Amplicor; Roche Diagnostic, Basel, Switzerland) PCR on leukocytes and plasma. Quantitative plasma viral load was determined using a commercial PCR kit (CMV Monitor; Roche Diagnostic). Patients were analyzed according to their pretransplantation CMV serological status (R- or R+). RESULTS: Seventeen patients developed CMV disease after transplantation. Qualitative leukocyte PCRs had the best overall sensitivity (54-69%) and specificity (75-87%) in identifying R- recipients with CMV disease before onset. The specificities of qualitative PCRs for R+ recipients were poor and, if used, could result in unnecessary preemptive treatment in up to 50% of patients. Symptomatic and asymptomatic R+, but not R-, recipients could be distinguished using a plasma viral load of 25,000 copies/ml. An increase in viral load of >0.7 log (fivefold) per week also distinguished between symptomatic and asymptomatic R+ recipients with high sensitivity (100%) and specificity (95%). CONCLUSIONS: Qualitative leukocyte PCRs were the best assays to predict CMV disease for R- recipients who received R+ kidneys. None of the qualitative assays could be used to guide preemptive therapy of R+ recipients, but plasma viral load and its incremental rate could be used as diagnostic tools in R+ recipients.

Pregnancy does not adversely affect renal transplant function.

Women with functioning transplanted kidneys often become fertile again. Indeed, renal function, endocrine status and libido rapidly improve after renal transplantation, and 1:50 women of childbearing age become pregnant. However, there is concern regarding the haemodynamic changes of pregnancy, which could lead to a decline in graft function (temporary or permanent). We examined obstetric data and renal parameters in 29 patients and 33 pregnancies. Mean serum creatinine and creatinine clearance remained stable throughout pregnancy and 1 year postpartum. However, there was a significant increase in proteinuria from a mean of 0.45 g/24 h around the time of conception to 1.11 g/24 h at delivery (p<0.05). The proteinuria resolved to baseline levels at 3 months postpartum. We highlight certain parameters to be considered before conception to allow a good obstetric outcome and prolong stable renal function: serum creatinine <150 micromol/l, proteinuria <1 g/day, absence of histological evidence of chronic allograft rejection, controlled blood pressure (140/90) and stability of maintenance immunosuppression.

Use of contrast-enhanced ultrasound in follow-up after endovascular aortic aneurysm repair.

PURPOSE: To investigate the use of contrast-enhanced ultrasound in the detection of endoleak after endovascular repair of abdominal aortic aneurysm. MATERIALS AND METHODS: Eighteen patients underwent follow-up on 20 occasions after endovascular aortic aneurysm repair by arterial-phase contrast-enhanced spiral computed tomography (CT). All patients had unenhanced color Doppler ultrasound and Levovist-enhanced ultrasound on the same day. The ultrasound examinations were reported in a manner that was blind to the CT results. CT was regarded as the gold standard for the purposes of the study. RESULTS: There were three endoleaks shown by CT. Unenhanced ultrasound detected only one endoleak (sensitivity, 33%). Levovist-enhanced ultrasound detected all three endoleaks (sensitivity, 100%). Levovist-enhanced ultrasound indicated an additional six endoleaks that were not confirmed by CT (specificity, 67%; positive predictive value, 33%). In one of these six cases, the aneurysm increased in size, which indicates a likelihood of endoleak. Two of the remaining false-positive results occurred in patients known to have a distal implantation leak at completion angiography. CONCLUSION: In this small group of patients, contrast-enhanced ultrasound appears to be a reliable screening test for endoleak. The false-positive results with enhanced ultrasound may be due to the failure of CT to detect slow flow collateral pathways. Although the number of patients in this study is small, enhanced ultrasound may be more reliable than CT in detecting endoleak.

Flow patterns in the radiocephalic arteriovenous fistula: an in vitro study.

A significant number of late failures of arteriovenous fistulae for haemodialysis access are related to the progression of intimal hyperplasia. Although the aetiology of this process is still unknown, the geometry of the fistula and the local haemodynamics are thought to be contributory factors. An in-vitro study was carried out to investigate the local haemodynamics in a model of a Cimino-Brescia arteriovenous (AV) fistula with a 30 degrees anastomotic angle and vein-to-artery diameter ratio of 1.6. Flow patterns were obtained by planar illumination of micro-particles suspended in the fluid. Steady and pulsatile flow studies were performed over a range of flow conditions corresponding to those recorded in patients. Quantitative measurements of wall shear stress and turbulence were made using laser Doppler anemometry. The flow structures in pulsatile flow were similar to those seen in steady flow with no significant qualitative changes over the cardiac cycle. This was probably the result of the low pulsatility index of the flow waveform in AV fistulae. Turbulence was the dominant feature in the vein, with relative turbulence intensity > 0.5 within 10 mm of the suture line decreasing to a relatively constant value of about 0.10-0.15 between 40 and 70 mm from the suture line. Peak and mean Reynolds shear stress of 15 and 20 N/m2, respectively, were recorded at the suture line. On the floor of the artery, peak values of temporal mean and oscillating wall shear stress of 9.22 and 29.8 N/m2, respectively. In the vein, both mean and oscillating wall shear stress decreased with distance from the anastomosis.

Vascular surgical society of great britain and ireland: endovascular aneurysm repair: the need for randomized controlled trials

BACKGROUND: An audit of endovascular aneurysm repair (EVAR) was undertaken in order to assess the efficacy of this new approach in the treatment of abdominal aortic aneurysm. METHODS: An international register of EVAR was started in 1996, with emphasis on close follow-up. RESULTS: Data have now been accumulated for 895 cases. The 30-day mortality rate is low at 3 per cent; patients who died generally had major co-morbidity. At discharge 14 per cent were identified as having an endoleak (persistent blood flow outside the lumen of the endoluminal graft but within the aneurysm sac) and another 18 per cent developed new endoleaks during the first year of follow-up. Continued expansion of the aneurysm was observed in 22 per cent. This occurred in 53 per cent of patients with an identified endoleak compared with 11 per cent of those in whom no endoleak was demonstrated (P < 0.01). Aneurysm rupture after EVAR occurred in six patients, three of whom died. CONCLUSION: That EVAR is technically feasible is beyond doubt. Close follow-up has identified problems specific to the minimally invasive approach. The significance of endoleaks in particular remains unclear, but the strong association with continued aneurysm expansion is of concern. The primary purpose of EVAR, however, is to prolong life and in this study the cumulative 2-year survival rate (including operative deaths) was 85 per cent. In patients without any complications the benefits of the minimally invasive approach are readily apparent. Thus, while there is no place for unrealistic optimism, there certainly appears to be a role for EVAR. To prevent inappropriate widespread application of this new approach, or indeed unwarranted condemnation, randomized controlled trials comparing EVAR with conventional management are essential.

Longitudinal aneurysm shrinkage following endovascular aortic aneurysm repair: a source of intermediate and late complications.

PURPOSE: To report the incidence of delayed complications following endovascular abdominal aortic aneurysm (AAA) repair and the relationship of these sequelae to morphological changes in the sac and endograft. METHODS: Twenty-six AAA patients treated with Vanguard endografts had completed > or = 1-year follow-up. Postoperative angiograms and spiral computed tomographic (CT) scans with 3-dimensional reconstruction were compared to the 1-year images to determine morphological changes in the aneurysm sac and the endograft. These changes were then related to complications occurring between 1 and 12 months postoperatively in the study group. RESULTS: Comparison of angiograms uncovered endograft buckling in 18 (69%) patients and acutely angled or kinked endografts in 10 (38%). Measurements from the CT scans found that undistorted endografts had a mean change in sac length of +6.6 mm. Mean sac length change in buckled endografts was -3.1 mm, while kinked endografts displayed a mean change of -6.2 mm (p < 0.002, Student's t-test). Five (19%) patients, all with distorted endografts, demonstrated late (1 to 12 months) complications (4 endoleaks and 1 graft limb thrombosis) owing to component separation, distal stent migration, and acute angulation. No movement in the proximal stent was observed. Elongation of the endograft (flow line measurement) was observed in one tube graft only. CONCLUSIONS: In this study, longitudinal shrinkage of the sac following endovascular aortic aneurysm repair led to buckling or kinking of the endograft within 1 year in 69% of patients. This appears to be an important source of delayed complications.