Vascular access 2007.

Over the past decades, vascular access management has undergone profound changes resulting in marked improvements in patient care. AV fistulae remain the access of choice and continue to represent the majority of accesses in most countries. Access monitoring is more widely available and new percutaneous therapies have revolutionized the therapeutic approach to access failure. Outpatient access centers providing both percutaneous and surgical therapies have decreased the need for vascular access related hospitalization. These advances have been supported by the development and promulgation of standardized evidence-based guidelines. These guidelines supported by national and international outcome data have helped rationalize vascular access care. Despite these advances many challenges remain. Catheter use has increased on a worldwide basis, with resultant increases in catheter related infections and complications including sepsis, endocarditis and paravertebral abscess. The availability and use of standardized chronic kidney disease care including early access placement in preparation for dialysis initiation remains underutilized in most settings. Payment system and structural barriers often provide disincentives for the efficient outpatient application of available technologies and there are a few available large prospective trials to help guide therapies. As we look to the future, it is anticipated that a wide range of new technologies will continue to improve vascular access management. Enhancing our delivery systems, combined with he thoughtful application of these technologies including new biologics, materials, interventional techniques and cellular technologies offer the promise of continued improvements in patients vascular access care over the coming decade.

Disease management improves ESRD outcomes.

Renal disease management organizations have reported achieving significant decreases in mortality and hospitalization in conjunction with cost savings, improved patient satisfaction and quality of life. Disease management organizations strive to fill existing gaps in care delivery through the standardized use of risk assessment, predictive modeling, evidence based guidelines and process and outcomes measurement. Patient self-management education and the provision of individual nurse care managers are also key program components. As we more fully measure clinical outcomes and total health-care costs including payments from all insurance and government entities, pharmacy costs and out-of-pocket expenditures, the full implications of disease management can be better defined. The results of this analysis will have a profound influence on United States healthcare policy. At present, current data suggests that the promise of disease management, improved care at reduced cost, can and is being realized in ESRD.

Dedicated outpatient vascular access center decreases hospitalization and missed outpatient dialysis treatments.

Dedicated outpatient vascular access centers (VAC) specializing in percutaneous interventions (angiography, thrombectomy, angioplasty and catheter placement) provide outpatient therapy that can obviate the need for hospitalization. This paper reports the impact of one VAC staffed by interventional nephrologists on vascular access-related hospitalization and missed outpatient dialysis treatments. We performed a retrospective analysis of vascular access-related hospitalized days and missed vascular access-related outpatient dialysis treatments from 1995 to 2002 in 21 Phoenix Arizona Facilities (5928 cumulative patients) and 1275 cumulative Fresenius Medical Care North America (FMCNA) facilities (289,454 cumulative patients) to evaluate the impact of the introduction of a VAC in Phoenix. Vascular access-related hospitalized days/patient year and missed dialysis treatments/patient year declined from 1997 to 2002 across all access types. The decline was greater in Phoenix and coincided with the creation of a VAC in 1998. By 2002, there were 0.57 fewer hospitalized days/patient year and 0.29 fewer missed treatments/patient year than in the national sample (P<0.01). In 2002, the relative risk for vascular access hospitalized days was 0.38 (95% confidence interval (CI) 0.27-0.5) (P<0.01) and for vascular access-related missed outpatient dialysis treatments was 0.34 (95% CI 0.24-0.49) (P<0.01) in Phoenix vs FMCNA after adjustment for age, gender, diabetic status duration of dialysis and access type. VAC development was associated with a significant decrease in vascular access-related hospitalization and missed outpatient dialysis treatments. Further studies are necessary to demonstrate this effect in other communities.

Antibodies to prothrombin, factor V, and beta2-glycoprotein I and vascular access thrombosis.

We studied 88 hemodialysis patients for the presence of antibodies to human factor II (hFII), bovine factor V (bFV), and human beta2-glycoprotein 1 (beta2GPI). Forty-one patients had elevated anti-hFII antibodies, 17 had elevated anti-bFV antibodies, and 9 had elevated anti-beta2GPI antibodies. Fifty-two patients had elevated antibodies to one or more protein. Patients with PTFE grafts had elevated antibodies most frequently (21 [75%] vs. 20 fistulas [45%; p = 0.016 compared with PTFE] and 11 tunneled catheters [68.8%]). Twelve of 13 patients (92.3%) with PTFE grafts and thrombosis had elevated antibody levels, compared with 9 of 15 without thrombosis (60%; p = 0.049). The number of thromboses and mean thrombosis rates were significantly higher in PTFE patients with antibodies (1.24 vs. 0.14 thromboses, p < 0.01; 42.67 vs. 6.44 thromboses/100 patient years, p < 0.05). When analyzed individually, thrombotic complications occurred more frequently in patients with PTFE grafts and elevated anti-bFV antibodies (p = 0.016), but did not correlate with anti-hFII or anti-beta2GPI antibodies. Thrombotic complications did not correlate with elevated antibody levels in patients with AV fistulas or cuffed catheters. In conclusion, hemodialysis patients with PTFE grafts frequently have elevated antibodies to FII, FV, and beta2GPI, and the presence of elevated antibody levels to one or more of these proteins is associated with an increased thrombotic risk. Further studies are necessary to determine whether limiting exposure to bovine thrombin preparations will decrease the incidence of these antibodies and PTFE graft thrombosis.

Increasing AV fistulas: revisiting a time-tested solution.

Despite having the lowest complication rate of all hemodialysis accesses, the prevalence of autologous arteriovenous (AV) fistulas has declined to 28% in the United States. The reasons for this decline include high early AV fistula failure rates, long maturation times, the frequent need for emergent dialysis, unavailable or poor pre-ESRD programs and planning, patient resistance to the realities of impending ESRD, and financial disincentives to AV fistula placement. Despite these barriers, programs throughout the country have demonstrated the ability to increase AV fistula prevalence to more than 50%. The strategies employed have included increased reliance on upper arm brachiocephalic and transposed basilic vein fistulas, the use of preoperative imaging to identify the best sites for fistula creation, and aggressive attempts at salvage of nonmaturing fistulas. Other groups have systematically and successfully replaced failed grafts with upper arm brachiocephalic or bracheobasilic fistulas. These experiences clearly show that exceeding the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) goal of more than 50% fistula placement is achievable in the United States. Declining numbers of AV fistulas are the result of a combination of factors, including changes in our patient population and learned practice patterns coupled with a failure of our delivery system to provide education, timely referral, and incentives for fistula placement. Increasing AV fistula prevalence in the United States is achievable and will improve patient outcomes and decrease the costs of ESRD.

Antibodies to topical bovine thrombin correlate with access thrombosis.

Bovine thrombin is often used topically to promote hemostasis during vascular surgery, including dialysis-access placement. Patients frequently develop antibodies to bovine thrombin preparations, and some may develop antiphospholipid antibodies. We evaluated 88 hemodialysis patients for the presence of antibodies to topical bovine thrombin to determine if elevated antibody levels correlated with vascular access thrombosis. Twenty-seven patients (30.7%) had elevated antibody levels to topical bovine thrombin. More patients with elevated antibody levels had prior vascular access thrombosis than patients with normal antibody levels (13 of 27 versus 5 of 61 patients; P < 0.001). This difference was almost entirely the result of greater levels of thrombosis in patients with polytetrafluoroethylene (PTFE) grafts and elevated antibody levels. In these patients, 11 of 13 patients (84.6%) with elevated antibody levels had a previous thrombosis compared with 2 of 15 patients (13. 3%) with normal antibody levels (P < 0.001). Patients with elevated antibody levels and PTFE grafts also had more prior thromboses (1.92 +/- 1.60 versus 0.133 +/- 0.35 thromboses; P < 0.01) and a greater thrombosis rate (66.89 +/- 63.71 versus 4.65 +/- 12.05 thromboses/100 patient-years; P < 0.01) than patients with normal antibody levels. There were no differences in the frequency of myocardial infarction, coronary artery bypass, access age, presence of diabetes mellitus, platelet counts, anticardiolipin antibody, albumin, lactate dehydrogenase, or C-reactive protein levels. In conclusion, patients with PTFE grafts and elevated antibody levels to topical bovine thrombin had significantly more vascular access thrombosis.

Intervention based on monthly monitoring decreases hemodialysis access thrombosis.

We randomized 103 patients (68 arteriovenous [AV] fistulas, 35 polytetrafluoroethylene [PTFE] grafts; mean follow-up 197 days) to monthly measurement of access flow (QAT), monthly measurement of static venous pressure (VPS), or no monthly monitoring (control patients) to determine whether access thrombosis would decrease. Patients with access flow <750 cc/min or with static venous pressure > or =0.5 were referred for angiography and angioplasty of stenotic lesions > or =50%. Six of sixty-two (9.7%) of monthly monitored patients (MM) developed access thrombosis vs. 9 of 41 (22%) of control patients (p<0.05). Fewer MM patients developed thrombosis in AV fistulas (2.4% [2 of 42] vs. 15.4% [4 of 26] control patients; p<0.05). Monthly monitored patients had fewer thrombotic episodes than control patients (19 vs. 125 per 100 patient-years; p<0.01). Thrombosis rates were lowest in patients receiving monthly access flow measurement (5.9 [QAT] vs. 30.3 per 100 patient-years [VPS]; p<0.05). In conclusion, intervention based on monthly access flow measurement or static venous pressure decreased hemodialysis access thrombosis. Measurement of access flow tended to result in lower thrombosis rates than after static venous pressure. We believe that monthly access flow measurement will ensure the lowest incidence of thrombosis and decrease the cost of access maintenance.

Assessment of hemodialysis access performance by color-flow Doppler ultrasound.

Hemodialysis access failure is a major cause of morbidity for patients with end stage renal disease with costs in excess of $743 million annually. Color-flow doppler ultrasound is the only mobile noninvasive technique that provides direct visual imaging of the access and measurement of access flow. Doppler ultrasound can identify patients at increased risk of future thrombosis and allow preventive intervention. Prospective trials show that ultrasound-based access management programs can decrease thrombosis rates, prolong access longevity, and decrease the cost of hemodialysis access management. It should be included as part of a coordinated program of hemodialysis management.

A novel approach to the detection of classical swine fever virus by RT-PCR with a fluorogenic probe (TaqMan).

Detection of classical swine fever virus (CSFV) and its discrimination from other pestiviruses can be achieved by virus isolation (VI) in cell cultures, antigen detection, or molecular analysis. To simplify the latter, a 5'-nuclease assay (TaqMan) was developed for the rapid and specific detection of CSFV with the minimum of downstream PCR processing. A pair of 5'-non-coding region, panpestivirus-specific PCR primers were assessed in a one-step reverse transcription-PCR with each of 36 diverse pestiviruses. The PCR products were subsequently reamplified, in conjunction with a CSFV-specific fluorogenic probe, in a nested-PCR with a second set of panpestivirus PCR primers. During nested PCR, when the target of interest was present, the CSFV probe annealed to the amplicon between the forward and reverse primers and was subsequently cleaved via the 5'-3' nucleolytic activity of the DNA polymerase resulting in the release of the fluorescent reporter dye. Each PCR tube was then placed directly into a luminescence spectrometer to monitor for any increase in fluorescence due to cleavage of the probe. This assay detected representatives of all genetic sub-groups of CSFV, but gave negative results for other pestiviruses. A preliminary assessment showed that the method could be used to detect CSFV RNA extracted from infected pig blood with a sensitivity greater than that of VI.

Identifying a new reality: zero vascular access recirculation using ultrasound dilution.

Access recirculation measurements by blood urea nitrogen (BUN) sampling methods have come under recent criticism regarding their reliability especially at low levels of recirculation. New methods have shown that the majority of patients have much less recirculation than previously suspected. However, some of these methods are prone to the same factors that limit BUN measurement accuracy. A new method, ultrasound dilution, was studied that avoids these problems and supports a new clinical reality--zero access recirculation. Information on the relationship of recirculation to access flow was also obtained which supports the assumption that patients with adequate vascular access flows have no recirculation.

Prolongation of hemodialysis access survival with elective revision.

153 hemodialysis accesses (56 fistulas and 97 PTFE grafts) were followed from placement to see if elective intervention prolonged access survival. The mean follow-up was 772 days (minimum 14 days, maximum 2755 days). Patients who expired, were transplanted or transferred were excluded. The groups of fistulas and grafts were subdivided into those whose first intervention was an episode of clotting versus those whose first intervention was an elective revision (either surgical repair or angioplasty of an area of stenosis within the access or run-off). These groups were compared to see whether electively revising an access prior to clotting would change the ultimate longevity of the access when compared to repairing the access after clotting. PTFE grafts with an initial elective intervention had an improved survival compared to grafts that clotted first (1023 days vs 689 days, p = 0.01). The electively revised grafts had fewer subsequent clotting episodes (1.1 clots per patient year vs 3.6, p = 0.02) and fewer interventions (1.8 interventions per patient year vs 3.7, p = 0.06). In fistulas, an initial elective revision increased access longevity when compared to repair after the fistula clotted (999 days vs 358 days, p = 0.005). Clotting episodes were decreased in those electively revised (0.5 clots per patient year vs 4.8, p = 0.014). Total interventions per patient year were also lower in those electively revised (1.2 vs 5.3, p = 0.028). In conclusion, elective correction of abnormalities in PTFE grafts and in AV fistulas prolongs access life when compared to repair after an initial episode of clotting. Elective revision also decreased the subsequent number of clotting episodes per patient year and the total number of interventions (revisions and declottings) per patient year in both grafts and fistulas.

Production, characterization and reactivity of monoclonal antibodies to porcine reproductive and respiratory syndrome virus.

This report describes the preparation of six monoclonal antibodies (MAbs) raised against a British isolate of porcine reproductive and respiratory syndrome virus (PRRSV), their characterization in terms of protein specificity and their reactivity with different PRRS viruses from Europe and the USA. Radioimmunoprecipitation and Western blotting studies of MAb reactivity with proteins from cell lysates of infected cells and purified virus revealed that four of the six MAbs (WBE1 and WBE4-6) precipitated a 15 kDa viral protein. Further studies using in vitro translated products of the Lelystad virus genome showed that this protein was the product of ORF7, the putative nucleocapsid protein. The specificity of another MAb, WBE2, was found to be for a 45 kDa protein, determined to be the product of ORF3 and demonstrated to be present in purified virion preparations. The protein specificity of the sixth MAb, WBE3 could not be determined. Thirty-three PRRSV isolates from Europe and the USA were grown in alveolar macrophages and examined by immunoperoxidase staining, using the panel of six MAbs. All European isolates were recognized by the four MAbs specific for the putative nucleocapsid, but the viruses showed different patterns of reactivity with WBE2 and WBE3. Furthermore, these two MAbs stained only a small proportion of the cells infected with certain isolates, suggesting that a single isolate may be antigenically heterogeneous. No MAbs bound to US isolates, indicating a consistent antigenic difference between the putative nucleocapsid of US and European isolates. Detergent extraction of cell lysate antigen abrogated the binding of WBE1-3, suggesting that the epitopes are conformation dependent.

Identification of herd-specific bovine viral diarrhoea virus isolates from infected cattle and sheep.

Thirteen pestiviruses isolated from ruminants on four different farms in Sweden were compared antigenically and genetically. On two farms, viruses were isolated from both cattle and sheep, a third farm contained only sheep and a fourth only cattle. Seven viruses were isolated from six different cattle and six viruses were isolated from five different sheep. Epitope conservation between the viruses was studied with a panel of 32 monoclonal antibodies, revealing that all of the isolates were BVDV-like. However, certain epitopes present in isolates from cattle were lost following virus transmission to sheep. In vitro amplification of the 5'-untranslated region of the 13 isolates by the polymerase chain reaction (PCR) and subsequent analyses of amplified products with restriction enzymes also indicated that all 13 isolates belong to the BVDV group of pestiviruses. A fragment of the E2 (gp53) gene of each virus was amplified by PCR and a comparison of the amplified sequence of 188 nucleotides separated the isolates into four groups each of which could be identified with a particular farm of origin. The 13 isolates were thus herd-specific rather than species-specific demonstrating that BVDV is readily transmitted between cattle and sheep.

A proposed division of the pestivirus genus using monoclonal antibodies, supported by cross-neutralisation assays and genetic sequencing.

Sixty-six pestiviruses from ruminant and porcine hosts were analysed with a panel of 76 monoclonal antibodies raised against 9 different viruses. Reactivity was used to construct epitope similarity maps for all of the viruses. Four principal virus subgroups were demonstrated. One subgroup equated to classical swine fever virus (CSFV) and included most porcine pestiviruses but none from ruminants. A second subgroup contained mainly viruses of bovine origin, including reference bovine viral diarrhoea viruses (BVDV) such as NADL; however viruses from pigs and sheep were also represented. A third subgroup represented by reference strains of border disease virus (BDV) comprised mainly ovine isolates, but also viruses from pigs. The fourth and most recently defined subgroup contained no reference strains of CSFV, BVDV or BDV, but included atypical viruses from cattle, sheep and pigs. The subgrouping scheme was supported by genetic comparisons between representative viruses from the 4 subgroups and by virus neutralisation with polyclonal sera.

Classical swine fever: genetic detection and analysis of differences between virus isolates.

Two pairs of oligonucleotide primers were designed that specifically amplified regions of the classical swine fever virus genome. These products, corresponding to a 671 bp portion of the genes encoding the E1 and E2 (gp33 and gp55) proteins and a 1090 bp portion of the putative polymerase gene, were amplified from eight virus isolates which had been responsible for a series of classical swine fever outbreaks in Italy involving both domestic pigs and wild boar. For each virus the fragments were partially sequenced to give 475 bp of the E1/E2 glycoprotein and 212 bp of the putative polymerase gene sequences. The data from each set of fragments were compared with one another and with reference strains. This allowed us confidently to assign most of the viruses to one of three subgroups. An analysis of the same viruses with a panel of monoclonal antibodies was much less informative. The subgrouping of the isolates suggested that, in this region of Italy, there had been at least two separate introductions of classical swine fever over a 7 year period and that virus had been transmitted between domestic pigs and wild boar. A consensus nucleotide sequence derived from the glycoprotein fragments of all the viruses examined revealed conservation at the wobble position of some codons.

Pharmacomechanical thrombolysis with urokinase for treatment of thrombosed hemodialysis access grafts. A comparison with surgical thrombectomy.

Seventy-one consecutively occluded polytetrafluoroethylene (PTFE) grafts treated with pharmacomechanical thrombolysis were compared with 75 surgical controls. The patients undergoing thrombomechanical lysis had a comparable rate of successful declotting (91% vs. 90.7%) and no significant difference in patency at 24 and 48 hr, 1 week, and 1 and 6 months. Patients undergoing thrombolysis required less overnight hospitalization (17 vs. 82%) (P < 0.001) and their hospital stays averaged 1.03 days versus 3.43 days in the surgical thrombectomy group (P < 0.0001). Complication rates were similar in both groups. Hospital charges and physician fees were significantly lower in the thrombolysis group, with total charges averaging $6,802 versus $12,740 (P = 0.0018). These cost differences were maintained even when patients with extended stays were excluded. In conclusion, pharmacomechanical thrombolysis provides efficacy and complications comparable to surgical thrombectomy, with the benefits of a decreased rate of hospitalization, decreased total number of days of hospitalization, and significant cost savings. The authors determined that pharmacomechanical thrombolysis is the preferable first intervention for acutely occluded PTFE grafts.

Border disease virus: delineation by monoclonal antibodies.

Many ovine pestiviruses from Britain and a number of atypical porcine isolates are largely unrecognised by monoclonal antibodies (mAbs) specific for reference strains of classical swine fever virus and bovine viral diarrhoea virus (BVDV). Additional mAbs have therefore been produced using some of these "unreactive" pestiviruses. Two of the viruses used were atypical porcine isolates (strains 87/6 and Vosges), whilst another had been isolated from a sheep (59386). Thirty-three mAbs were selected, none of which recognised two reference strains of BVDV, but three of which recognised the Alfort strain of classical swine fever. On the basis of radioimmunoprecipitation they were considered to be directed at one of three different pestivirus proteins (gp 53, gp 48 or p 125). Three virus subgroups were evident when the mAbs were used to type 16 ovine and two atypical porcine pestiviruses. One subgroup contained the Vosges and 59386 viruses and four ovine field isolates. The second subgroup comprised the 87/6 virus, the Moredun and Aveyron reference strains of border disease virus and four further ovine field isolates. Three of four ovine viruses making up the third subgroup had been previously categorised as BVDV-like and were largely unrecognised by the new mAbs. The findings were in agreement with previous attempts to segregate some of the same viruses using partial genomic comparisons or cross-neutralization tests.