Jan H. M. Tordoir

Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques

OBJECTIVE To study the amount and phenotype of DNA-synthesizing and apoptotic cells during atherogenesis. METHODS Atherosclerotic lesions (n = 76), obtained at autopsy (N = 6) or during vascular surgery (N = 8), were classified [type I-VI; American Heart Association (AHA) classification], immunolabeled with MIB 1 or the TUNEL technique and double stained with cell-type-specific antibodies. Subsequently, the labeled fractions were quantified. RESULTS In type II-VI lesions, intimal DNA synthesis was increased compared to that of the non-diseased (ND) arterial wall. DNA synthesis peaked in early type II lesions (2.7 +/- 0.5 vs. 0.02 +/- 0.02% in ND; p < 0.05), and declined to 0.7 +/- 0.2% in type V lesions (p < 0.05). Interestingly, a second peak of DNA synthesis of 1.7 +/- 0.1%, was observed in type VI (ruptured plaque) lesions. Double staining revealed that DNA synthesis was mostly confined to the macrophage-derived foam cell (51.9%). In type II lesions, 100.0% of all DNA-synthesizing cells were present in the intimal foam cell-rich area, while in advanced type III, IV and V lesions, DNA synthesis had shifted to the shoulder region (74.8, 78.5 and 68.1%, respectively). In type VI lesions, DNA synthesis was present in the area underlying the plaque rupture (52.7%). Apoptosis was only elevated in advanced type IV, V and VI lesions (0.8 +/- 0.1, 0.8 +/- 0.1 and 1.1 +/- 0.1%, respectively, vs. 0.0 +/- 0.0% in ND) and was predominant in the lipid core (90.5% in type IV lesions; 54.2% in type V lesions) or equally divided between the lipid core and the region underlying the plaque rupture (31.8 and 34.6% in type VI lesions). In type III-VI lesions, 50.0, 38.9, 42.6 and 42.8% of the TUNEL-positive cells were macrophages. CONCLUSIONS In stable atherosclerotic lesions, DNA synthesis is an early event, while apoptosis is a late event. Ruptured plaques show a second peak of cell turnover. Lastly, cell turnover is mostly confined to the macrophage-derived foam cell.

Buttonhole needling of haemodialysis arteriovenous fistulae results in less complications and interventions compared to the rope-ladder technique

BACKGROUND The rope-ladder puncture technique, with cannulation along the whole length of the vessel traject, has been very common in haemodialysis patients with autogenous arterio-venous fistula (AVF). Todays dialysis population with AVF may exhibit difficult cannulation, because of a short vein length or a complicated cannulation route. An alternative needling possibility is the buttonhole (BH) technique, which inserts needles at exactly the same location during every dialysis session. The present study was conducted to investigate the effect of both cannulation techniques on the incidence of vascular access (VA) complications. METHODS A total of 75 prevalent haemodialysis patients with autogenous AVF using the BH technique were compared with 70 patients using the rope-ladder technique. The following parameters were registered: haematoma occurrence, redness, swelling, aneurysm formation, the use of sharp or dull needles, miscannulations, and interventions. Needling pain and fear of puncture were assessed using a verbal rating scale (VRS). The duration of the follow-up was 9 months. RESULTS Patients in the BH group had more unsuccessful cannulations, compared with the rope-ladder method (P < 0.0001), but the frequency of haematoma (P < 0.0001) and aneurysm formation (P < 0.0001) was less. In addition, intervention such as angioplasty (P < 0.0001) was higher in patients using the rope-ladder technique. A negative outcome of the BH technique was the higher incidence of access infections compared to the rope-ladder method. CONCLUSION This study showed that the BH method is a valuable technique with few complications like haematoma, aneurysm formation and the need for interventions. However, the infections induced by the BH method should not be underestimated. This underlines the importance of an aseptic and correct technique of the buttonhole procedure.

Duplex ultrasound scanning in the assessment of arteriovenous fistulas created for hemodialysis access: Comparison with digital subtraction angiography

The results of duplex ultrasound scanning for the diagnosis of stenoses in Brescia-Cimino arteriovenous fistulas and graft arteriovenous fistulas created for hemodialysis access are reported. Quantitative Doppler spectrum analysis of 64 arteriovenous fistulas was correlated with the outcome of digital subtraction angiography. The best Doppler parameter for the detection of a stenosis was the peak systolic frequency. In graft arteriovenous fistulas the use of this parameter resulted in a diagnostic accuracy of 86%, a sensitivity of 92%, and a specificity of 84% in the detection of stenoses. In Brescia-Cimino arteriovenous fistulas the diagnosis of anastomotic stenoses was possible with a diagnostic accuracy of 81%, a sensitivity of 79%, and a specificity of 84%. Measurement of peak systolic frequency ratios or end-diastolic frequencies had no additional diagnostic value for the detection of stenoses. The diagnosis of efferent vein stenoses was very accurate with duplex investigation (accuracy 96%, sensitivity 95%, and a specificity of 97%. We conclude that duplex scanning is a promising noninvasive method for the diagnosis of stenoses in arteriovenous fistulas created for hemodialysis access.

Hemodynamics and complications encountered with arteriovenous fistulas and grafts as vascular access for hemodialysis : A review

This review article describes the current state of affairs concerning in vivo, in vitro and in numero studies on the hemodynamics in vascular access for hemodialysis. The use and complications of autogenous and non-autogenous fistulas and catheters and access port devices are explained in the first part. The major hemodynamic complications are stenosis, initiated by intimal hyperplasia development, and thrombosis. The different in literature proposed conceivable causes of intimal hyperplasia development like surgical interventions, compliance mismatch, wall shear stress (WSS) and shear rate, vessel wall thrill and blood pressure are discussed on the basis of in vivo, in vitro and in numero studies.

Surgical or endovascular repair of thrombosed dialysis vascular access: Is there any evidence?

INTRODUCTION Endovascular and surgical strategies have been used to manage patients with thrombosed vascular access for hemodialysis. We analyzed the evidence to see whether endovascular or surgical treatment has the best outcome in terms of primary success rate and long-term patency. METHODS We performed a systematic literature search of endovascular and surgical repair of thrombosed hemodialysis vascular access. The analysis included meta-analysis, randomized, and population-based studies of thrombosed arteriovenous fistulae and grafts. RESULTS One meta-analysis and eight randomized studies on the treatment of arteriovenous graft thrombosis were identified. Studies conducted before 2002 demonstrated a significantly better primary success rate and primary and secondary patencies of surgical thrombectomy vs endovascular intervention. After 2002, similar results of both techniques have been reported. Only population-based studies on the treatment of thrombosed autogenous arteriovenous fistulae have been published, showing similar outcome of surgical and endovascular intervention in terms of primary success. The long-term primary and secondary patencies are slightly better for surgical treatment, but this concerns only forearm fistulae. CONCLUSIONS The outcome of endovascular and surgical intervention for thrombosed vascular access is comparable, in particular for thrombosed prosthetic grafts. Surgical treatment of autogenous arteriovenous fistulae is likely to have benefit compared with endovascular means. Definitive randomized trials are needed to provide the level 1 evidence to resolve this latter issue.

Diagnosis, prevention and treatment of haemodialysis catheter-related bloodstream infections (CRBSI) : a position statement of European Renal Best Practice (ERBP)

Nephrology Section, Department of Internal Medicine, University Hospital, Gent, Belgium, Nephrology, Dialysis and Intensive Care Unit, Lapeyronie University Hospital, Montpellier, France, Department of Renal Medicine, Royal Derby Hospital, Derby, UK, Nephrology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium, Nephrology Department, Consorcio Hospital General Universitario, Valencia, Spain and Vascular Surgery, Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands

Acute ischemic injury to the renal microvasculature in human kidney transplantation

Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury.

A new hemostatic puncture closure device for the immediate sealing of arterial puncture sites

After angiography, 6 to 24 hours of bedrest is indicated to assure that adequate hemostasis of the femoral artery has been achieved. Recently, a new hemostatic puncture closure device (HPCD) has been developed, which consists of a resorbable polymer anchor, a resorbable suture, a small collagen plug and an 8Fr delivery device. The device is delivered into the femoral artery through the introducer sheath, the anchor is secured against the intraluminal artery wall, and the collagen plug is deployed on the arterial wall. The prototype of the HPCD was used in 20 patients administered heparin. After insertion of the HPCD, hemostasis was achieved in 1.2 +/- 2.1 minutes; in 2 patients a light pressure dressing was applied for 4 hours to stop oozing. No late bleeding occurred. In 1 patient the positioning suture broke, requiring the application of a pressure bandage. Patients were uneventfully mobilized after 6.7 +/- 3.5 hours. In all patients serial duplex scanning of the femoral artery was performed before and after 1, 7, 30 and 90 days after HPCD placement. In 5 patients a small subcutaneous hematoma close to the site of introduction could be detected by ultrasound 1 day after catheterization. All but 1 patient had normalization of the flow patterns in the femoral artery. It is concluded that: (1) the HPCD is an effective device to achieve immediate hemostasis after arterial catheterization despite antithrombotic therapy, (2) early mobilization was uneventful, (3) duplex ultrasound studies demonstrated only transient changes in the punctured femoral artery, and (4) further investigations are needed to establish the efficacy and safety of the device.

Enhanced Cellular Proliferation in Intact Stenotic Lesions Derived From Human Arteriovenous Fistulas and Peripheral Bypass Grafts Does It Correlate With Flow Parameters

BACKGROUND Vascular interventions are often complicated by the development of intimal thickening, leading to stenosis. Cellular proliferation is a key event in stenosis formation in animals, but the role of cell proliferation in intimal thickening in humans is still unclear. Furthermore, the relation between proliferation in human stenotic lesions and flow parameters has not been established. METHODS AND RESULTS We studied the proliferation patterns of 35 anatomically intact human stenotic lesions derived from either peripheral bypasses (normal flow) or hemodialysis AV fistulas (high flow) with the use of Ki-67, a cell proliferation marker. Local flow parameters were assessed with ultrasound. Proliferation patterns were similar in AV fistula and bypass stenoses. In the intima, proliferation was highest in the area just below the endothelium (AV fistulas, 3.6%; bypasses, 3.5%; P = NS). In adjacent nonstenotic vessel segments that were used as controls, proliferation rate in the intima was 0.3%. Double-labeling studies revealed that subendothelial-intimal proliferation consisted mainly (90%) of vascular smooth muscle cells, whereas proliferation in the other layers of the vessel wall also consisted of endothelial cells and macrophages. Blood flow velocity was negatively correlated with subendothelial-intimal proliferation (r = -.61, P < .05). The endothelial cell coverage of the lumen was positively correlated with proliferation (r = .85, P < .01). CONCLUSIONS These data suggest enhanced cellular proliferation in human stenotic tissue derived from AV fistulas and peripheral bypass grafts. Furthermore, high proliferation rates seem to be associated with endothelial cell coverage of the lumen and low local flow velocities.

Catheter-related blood stream infections (CRBSI): a European view

Nephrology Section, Department of Internal Medicine, University Hospital, Gent, Belgium, Nephrology, Dialysis and Intensive Care Unit, Lapeyronie University Hospital, Montpellier, France, Department of Renal Medicine, Royal Derby Hospital, Derby, UK, Nephrology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium, Nephrology Department, Consorcio Hospital General Universitario, Valencia, Spain and Vascular Surgery, Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands