Unassisted Patency Research Articles

Prospective controlled pilot study of arteriovenous fistula placement using the novel Optiflow device

Arteriovenous fistula (AVF) maturation failure remains a significant problem with reported early failure rates around 50%. Suboptimal hemodynamics, variable surgical skills, and technique dependency are widely believed to contribute to AVF nonmaturation. The Optiflow (Bioconnect Systems, Ambler, Pa) is a novel anastomotic device placed in situ that has potential for improving hemodynamics and standardizing AVF placement. We report results from a prospective nonrandomized controlled pilot study designed to investigate the safety and performance of the Optiflow. Forty-one participants underwent AVF formation using either a 3-mm or 4-mm Optiflow and 39 matched control participants underwent AVF formation using the standard technique at two sites. Patients were observed for 90 days after AVF placement. The primary end point was unassisted maturation, which was defined as an outflow vein with a diameter ≥5 mm and blood flow ≥500 mL/min measured by Doppler ultrasound. The secondary performance end point was unassisted patency, and the primary safety end point was freedom from device-related serious adverse events. Unassisted maturation rates at 14, 42, and 90 days were 76%, 72%, and 68%, respectively, for the Optiflow group and 67%, 68%, and 76%, respectively, in the control group (P = .38, .69, and .47 at 14, 42, and 90 days). There was a trend to earlier maturation (assessed at 14 days) in the 4-mm Optiflow group compared with the control group (P = .059). There were no device-related serious adverse events. Maturation results for both the Optiflow and control groups were highly favorable compared with historical assisted maturation rates of approximately 50%. The Optiflow appears to be safe and effective in the placement of AVFs, with high maturation rates.

Role of far infra-red therapy in dialysis arterio-venous fistula maturation and survival: systematic review and meta-analysis.

IntroductionA well-functioning arteriovenous fistula (AVF) is the best modality for vascular access in patients with end-stage renal disease (ESRD) requiring haemodialysis (HD). However, AVFs’ main disadvantage is the high rate of maturation failure, with approximately one third (20%–50%) not maturing into useful access. This review examine the use of Far-Infra Red therapy in an attempt to enhance both primary (unassisted) and secondary (assisted) patency rates for AVF in dialysis and pre-dialysis patients.MethodWe performed an online search for observational studies and randomised controlled trials (RCTs) that evaluated FIR in patients with AVF. Eligible studies compared FIR with control treatment and reported at least one outcome measure relating to access survival. Primary patency and secondary patency rates were the main outcomes of interest.ResultsFour RCTs (666 patients) were included. Unassisted patency assessed in 610 patients, and was significantly better among those who received FIR (228/311) compared to (185/299) controls (pooled risk ratio of 1.23 [1.12–1.35], p = 0.00001). In addition, the two studies which reported secondary patency rates showed significant difference in favour of FIR therapy- 160/168 patients - compared to 140/163 controls (pooled risk ratio of 1.11 [1.04–1.19], p = 0.003).ConclusionFIR therapy may positively influence the complex process of AVF maturation improving both primary and secondary patency rates. However blinded RCTs performed by investigators with no commercial ties to FIR therapy technologies are needed.

Assessing the Approach to a Thrombosed AV Graft

The patency of the vascular access (VA) is a fight for the attending nephrologist. A retrospective observational study was conducted to compare the success rate of surgical versus endovascular technique percutaneous transluminal angioplasty (PTA) for graft thrombosis treatment. Of 3008 patients, 22.1% patients were dialyzed through grafts. Forty-five percent of all prevalent patients referred due to VA malfunction had a graft. For 18 months, 336 thrombosed grafts were submitted to surgery in 228 cases and to PTA in 126. PTA for thrombolysis included the Pharmaco-Mechanical Technique and the Arrow-Trerotola Device. Procedures were performed as outpatient, with an average delay of 1 day. Immediate success was 100% for surgery and 87.3% for PTA. The unassisted patency for thrombosed grafts for surgery/PTA was 265.12 ± 15.30/230.59 ± 19.83 days respectively, favoring surgery. The primary patency for thrombosed grafts treated by surgery/PTA at 30, 90, and 180 days was, respectively, 74.1%/81%, 63.2%/67.5%, and 53.9%/55.6% all in favor of PTA. AV grafts have a much higher rate of thrombosis than fistulas. Graft thrombosis can be dealt either by surgery or PTA, with identical success.

Arteriovenous Fistula Survival and Needling Technique: Long-term Results From a Randomized Buttonhole Trial

We previously have shown that buttonhole needling is associated with a reduction in hematoma and postulated that buttonhole needling may increase long-term survival of an arteriovenous fistula (AVF). The purpose of this study was to evaluate AVF survival and complications in buttonhole versus standard needling. Long-term follow up of a randomized controlled trial in which participants were randomly assigned to standard or buttonhole needling and followed up until the AVF was abandoned or the study end date. 140 long-term hemodialysis patients in Calgary, Alberta. Buttonhole needling with median time of exposure to the intervention of 13.2 (IQR, 7.8-19.4) months. Patients were prospectively followed up for study outcomes. Median follow-up times were 17.2 (IQR, 11.9-37.8) and 19.2 (IQR, 12.5-41.0) months for standard and buttonhole needling, respectively (P=0.2). The primary outcome was median access survival in months. Other outcomes included assisted and unassisted patency rates, rates of surgical and radiologic interventions, and time to abandonment (months) of buttonhole. Baseline characteristics were similar. The primary outcome, median access survival, was similar inboth groups: 16.0 (IQR, 10.6-29.3) and 18.4 (IQR, 10.9-32.7) months for standard and buttonhole needling, respectively (P=0.2). There were 7 (10.1%) and 6 (8.6%) thromboses with standard and buttonhole needling, respectively (P=0.6). Median fistulogram rates were similar between techniques (P=0.2 with intention-to-treat analysis). Most patients (46 of 70) abandoned buttonhole needling by a median of 11.3 (IQR, 4.8-18.2) months. Median time to first infection for buttonhole needling was 11.1 (IQR, 4.9-30.0) months. There were no infections in standard needling of AVFs. Findings are limited to patients needled by multiple hemodialysis nurses and not applicable to self-needlers. AVFs with buttonhole needling did not have improved survival. The lack of survival benefit and higher risk of infection should be noted when promoting buttonhole needling.

Arteriovenous Fistula Creation Using the Optiflow™ Vascular Anastomotic Connector: The Open (Optiflow PatEncy and MaturatioN) Study

Arteriovenous fistulas (AVFs) are the preferred form of vascular access for hemodialysis. However, non-maturation and patency are major clinical problems. The Optiflow™ device is an implantable anastomotic connector used to standardize the creation of an AVF. Studies have suggested that the geometry of the anastomosis and experience of the surgeon impact patency and maturation rates. The Optiflow serves as a surgical template whereby the geometry and flow path of the anastomosis are predetermined. This prospective study was intended to evaluate maturation, patency and safety of the Optiflow. Forty-one upper arm AVFs were created in 41 end-stage renal disease patients using the Optiflow device at two investigational sites. Patients were followed for 90 days with serial Doppler ultrasounds performed at approximately 14, 42 and 90 days to determine AVF maturation. The primary performance endpoint was unassisted maturation, defined as an outflow vein that was equal to or greater than 5 mm in diameter, and with flow equal to or greater than 500 mL/min without the need for any intervention intended to promote or maintain maturation. The primary safety endpoint was the rate of device-related serious adverse events. Unassisted maturation rates were 76%, 72% and 68% and unassisted patency rates were 93%, 88% and 78%, at 14, 42 and 90 days, respectively. There were no device-related serious adverse events. The results suggest that the Optiflow is safe for its intended use and could play an important role in enhancing AVF maturation while standardizing the anastomotic technique.

Translesional Pressure Ratio Predicts Technical Outcome and Patency in Angioplasty on Outflow Stenosis of Hemodialysis Graft

Translesional pressure ratio (TLPR) indicating fractional flow reserve has been applied to physiological assessment of moderate coronary stenosis. The role of TLPR in hemodialysis (HD) patients with arteriovenous graft (AVG) outflow stenosis undergoing percutaneous transluminal angioplasty (PTA) is unclear. The purpose of the study was to assess the validation of TLPR in such patients undergoing PTA. Patients with pure AVG outflow stenosis confirmed by angiography were prospectively enrolled. A TLPR defined as a ratio of the mean pressure downstream to the lesion(s) to the vein-sided intragraft pressure was measured using a catheter pullback method. Relationship among TLPR, angiographic result and clinical outcome within 6 months was detected. Of 65 PTAs, the post-PTA TLPR significantly increased (from 0.28±0.10 to 0.50±0.11; p<0.0001). A significantly greater pre-PTA TLPR was observed in the simple lesions at baseline compared with the complex lesions (0.32±0.09 vs. 0.20±0.06; p<0.0001). Post-PTA TLPR ≥0.5 was powerfully related to angiographic success (p<0.0001). The group with angiographic success plus post-PTA TLPR ≥0.5 had a longer PTA-free patency (208.7±188.7 vs. 109.8±67.7 days; p=0.013) compared with that with angiographic nonsuccess plus post-PTA TLPR <0.5. Our data show that TLPR correlates well with lesion properties and angiographic results, and helps predict following unassisted patency. The study suggests TLPR as a hemodynamic indicator during PTA.

Reconstruction of the Greater Saphenous Vein to Create a Viable Arterio-Venous Fistula Conduit

controlled trial of dipyridimole plus aspirin for newly placed AVG. Methods: Participants in the Dialysis Access Consortium trial with upper extremity prosthetic grafts of the brachial artery were studied. Multivariable analyses adjusting for treatment group, center, gender, race, BMI, diabetes, current dialysis, and prior access or catheter were performed to compare outcomes of forearm (fAVG) and upper arm (uAVG) grafts including loss of primary unassisted patency (LPUP) and cumulative primary graft failure (CGF). Subgroup analyses of graft configuration and outflow vein used were conducted. Results: Of the 522 participants with an upper extremity brachial artery graft, 269 had fAVG and 253 had uAVG. Participants with fAVG were less often male (33% vs 43%; P 1⁄4 .03), black (62% vs 77%; P < .001), dialysisdependent at time of surgery (20% vs 36%; P < .001), and had a higher mean BMI (32 vs 29; P < .001) compared to those with uAVG. There was no difference in LPUP (69% vs 78%; P 1⁄4 .22) or CGF (32% vs 36%; P 1⁄4 .53) between fAVG and uAVG at 1 year follow-up. Multivariable adjustment did not change the statistical significance of the association between AVG location and either LPUP (HR, 1.26; 95% CI, 0.98, 1.62; P 1⁄4 .07) or CGF (HR, 1.09; 95% CI, 0.80, 1.49; P 1⁄4 .58). LPUP did not differ significantly between fAVG and uAVG among subgroups based on AVGconfiguration (P1⁄4 .23) or outflow vein used (P1⁄4 .53). Conclusions: Patency of fAVG and uAVG was similar despite the larger caliber veins often encountered in the upper arm. Therefore, to preserve a maximal number of access sites, the forearm location should be considered first before resorting to an upper arm graft.

Primary balloon-expandable covered stents vs. primary bare-stents for mesenteric ischemia: patency and clinical outcomes

Purpose To evaluate the anatomical and functional outcomes of primary balloon-expandable covered stents compared to primary balloon-expandable bare-stents for the endovascular management of chronic mesenteric ischemia. Materials and Methods A retrospective audit of patients undergoing primary endovascular management of mesenteric ischemia was performed (01/2006-12/2011). The cohort was divided into bare-metal stent group (BMG) and covered stent (0.035-inch platform, V-12, Atrium) group (CVG). Inferior mesenteric artery (IMA) arteries (none in CVG) and angioplasty alone (small sample size) were excluded. Patency per artery was determined by imaging follow-up and clinical success (patency by clinical response). Results 111 primary endovascular procedures were found (18 IMA excluded). Technical success of SMA and CAx arteries was 99% (n=110/111). An additional 7 arteries (2 SMA, 5 CAx) in 6 patients were excluded (angioplasty alone). The remainder was: 15 (12 SMA, 3 CAx) arteries in 14 patients (CVG) and 88 (64 SMA, 24 CAx) arteries in 75 patients (BMG). Clinical success per patient for BMG vs. CVG was 87% (n=65/75) vs. 79% (n=11/14) (P=0.3933), respectively. Primary unassisted patency at 6, 9, 12 and 24 months for CVG vs. BMG were: 100%+/-0, 100%+/-0, 100%+/-0, and 100%+/-0 vs. 93%+/-4, 81%+/-6, 74%+/-8, and 45%+/-11, respectively (P Conclusion In patients with mesenteric ischemia, balloon-expandable covered stents have improved patency compared to balloon-expandable bare stents in the celiac axis and superior mesenteric artery.

Length polymorphisms of heme oxygenase-1 determine the effect of far-infrared therapy on the function of arteriovenous fistula in hemodialysis patients: a novel physicogenomic study

The objective of this study was to evaluate the interaction between the length polymorphism of the guanosine thymidine repeat [(GT)n] in the heme oxygenase-1 (HO-1) gene and far-infrared (FIR) therapy on access flow (Qa) and arteriovenous fistula (AVF) patency in hemodialysis (HD) patients. A total of 280 HD patients were randomized into a control group (n = 141) and the FIR group (n = 139) who received 40 min of FIR therapy three times weekly for a year during the study period from May 2005 to December 2007. Access flow was measured during HD. The [(GT)n] was determined with the definition of long (L) allele as [(GT)n] ≥ 30 and short (S) allele as [(GT)n] < 30. The Qa decreased from S/S to S/L and further to the L/L group but increased by FIR therapy with the highest Qa increase in the S/S group. The incidence of AVF malfunction decreased both from the L/L, S/L to S/S group (32.4 versus 17.2 versus 10.9%, P = 0.007) and from the control group to FIR group (27.5 versus 12.6%, P = 0.004). Significant associations were found between AVF malfunction and the following factors (hazard ratio, P-value): a past history of AVF malfunction (2.45, P = 0.044), FIR therapy (0.369, P = 0.03) and L/L genotypes of HO-1 (2.531 versus S/S + S/L genotypes). The 1-year unassisted patency decreased from 91.9 and 77.6% in S/S and S/L subgroups with and without FIR therapy to 75.8 and 60% for L/L subgroup with and without FIR therapy, respectively (P < 0.001). FIR therapy improves Qa and patency of AVF in HD patients, with the best protective effect in those with S/S genotype of HO-1.

Distal Radial Artery Pressures Predict Angiographic Result and Short‐Term Patency Outcome in Hemodialysis Patients With Juxta‐Anastomotic Inflow Stenosis of Radiocephalic Fistula Undergoing Transradial Angioplasty

Distal radial artery pressure (RAP) was observed to be reduced after transradial percutaneous transluminal angioplasty (PTA) on the juxta-anastomotic venous stenosis of radiocephalic arteriovenous fistula (RCAVF). Distal RAPs are easily obtained from a pressure transducer connected with an introducer retrograde inserted into distal radial artery. The clinical role of distal RAP in the setting of transradial PTA remains unknown. This prospective and observational study aimed to explore the relationship between distal RAPs and clinical outcomes. This study recruited hemodialysis patients with RCAVF juxta-anastomotic venous stenosis undergoing transradial PTA. RAP-related variables and procedural data before PTA (pre-PTA) and after PTA (post-PTA) were analyzed. The study endpoint was dysfunction-driven re-PTA during the 1-year follow-up. Overall, 73 PTAs significantly reduced the mean of systolic RAPs from 159.6 ± 41.4 to 108.4 ± 41.5 mm Hg; P < 0.0001. Post-PTA systolic RAP was associated with angiographic outcome (P = 0.004) and unassisted patency at 3 months (P = 0.036), but not at 6, 9, or 12 months (P > 0.05). The group with angiographically successful PTAs had a significantly lower mean of post-PTA systolic RAPs compared with that with unsuccessful PTAs (98.4 ± 35.4 vs. 128.7 ± 46.1 mm Hg; P = 0.003). The post-PTA systolic RAP may be seen as a predictor for 3-month unassisted patency (AUC = 0.669; P = 0.048). In conclusion, this study provides the RAP profile to help guide transradial PTA on RCAVF juxta-anastomotic venous stenosis and predict 3-month unassisted patency in a hemodynamic manner.

Fish Oil and Hemodialysis Graft Patency

MORE THAN 600 000 PATIENTS IN THE UNITED States have end-stage kidney disease, with the majority—nearly 400 000 patients— requiring long-term maintenance hemodialysis. Ready access to the bloodstream is essential for hemodialysis and may be provided by a surgically created arteriovenous fistula, arteriovenous graft, or central venous catheter. An arteriovenous fistula is preferred because of its lower risk of thrombosis and lower overall cost. However, delayed maturation and failure rates of 20% to 60% for new fistulas result in greater reliance on catheters, the least desirable type of hemodialysis access. Compared with a new fistula, an arteriovenous graft is easier to cannulate and can be used within a few weeks of surgical creation. Yet grafts are associated with a higher rate of thrombosis, with attendant increased morbidity and cost. Grafts were once the most common type of hemodialysis access in the United States. However, through the efforts of the Fistula First Initiative, the End-Stage Renal Disease Networks, and the medical community, the prevalence of grafts in the United States has recently declined to less than 25%. Given the challenges of fistula maturation, grafts remain an appealing option, if the problem of thrombosis can be solved. The underlying cause of thrombosis in grafts and fistulas is neointimal hyperplasia leading to stenosis, typically at the vein-graft or vein-artery anastomosis. Fish oil has measurable anti-inflammatory, antiproliferative, and antithrombotic effects as well as a salutary effect on endothelial function that could slow the development of neointimal hyperplasia and graft thrombosis. Fish oil has been shown to reduce distal occlusion in coronary vein grafts and is associated with lower overall cardiovascular disease mortality. In a small, randomized, placebo-controlled trial of 24 patients, supplementation with 4 g of fish oil daily (1 g/capsule, 4 capsules/d) decreased hemodialysis graft thrombosis from 75.6% to 14.9% at 1 year. In this issue of JAMA, Lok and colleagues report the results of a randomized placebo-controlled trial evaluating the effect of fish oil supplementation on patency of newly created hemodialysis grafts. Patients were randomized 7 days after graft surgery to receive either four 1-g capsules daily of fish oil (containing 400 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid per capsule) or matching placebo capsules taken for 12 months. The primary outcome was the proportion of patients with loss of primary unassisted graft patency, defined as the first graft thrombosis or a surgical or radiological intervention on the graft. Because of slow recruitment, the study was terminated early before reaching its target goal of 232 patients. A total of 201 patients were randomized; 5 dropped out before receiving treatment, 2 in the fish oil group and 3 in the placebo group. A total 196 patients were ultimately treated, 99 with fish oil and 97 with placebo. The analysis was based on patients who completed the study rather than those randomized. At 12 months, loss of primary unassisted graft patency occurred in 48% of patients who received fish oil and 62% who received placebo, for a relative risk reduction of 22%, a difference that did not reach statistical significance. However, predefined secondary outcomes that measured the rate of occurrence of events, including the number of primary events per 1000 access-days (incidence rate ratio) and the loss of primary unassisted patency by the Kaplan-Meier method (hazard ratio), revealed reductions of 42% and 32%, respectively, both of which were statistically significant. Although other predefined secondary graft outcomes including the rate of thrombosis and rate of radiological or surgical interventions were also significantly reduced, cumulative graft patency was not prolonged. As is consistent with other trials of fish oil, Lok et al reported a statistically significant reduction in systolic and diastolic blood pressure and a reduction in the cardiovascular event rate among patients who received fish oil. However, the latter finding should be interpreted with caution, given the small sample size and overall small number of events. Nonetheless, given the high mortality from cardiovascular disease in the hemodialysis population, this latter observation should stimulate an appropriately powered trial evaluating the effect of fish oil for prolonging patient survival. In the study by Lok et al, there was no between-group difference in triglyceride levels, which has usually been a re-

Use of Aspirin Associates with Longer Primary Patency of Hemodialysis Grafts

Extended-release dipyridamole plus low-dose aspirin (ERDP/ASA) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts, but the individual contributions of each component are unknown. Here, we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a randomized trial that compared ERDP/ASA and placebo in newly created grafts. We used Cox proportional hazards regression, adjusting for prespecified baseline comorbidities and covariates. Of all participants, 43% reported use of aspirin at baseline; of these, 82% remained on nonstudy aspirin (i.e., excluding ERDP/ASA) at 1 year. After 1 year of follow-up, the incidence of primary unassisted patency among participants using aspirin at baseline was 30% (95% CI: 24 to 35%) and among those not using aspirin was 23% (95% CI: 18 to 27%). Use of aspirin at baseline associated with a dose-dependent prolongation of primary unassisted graft patency that approached statistical significance (adjusted HR, 0.83; 95% CI: 0.68 to 1.01; P=0.06). Use of aspirin at baseline did not associate with prolongation of cumulative graft patency or participant survival. In conclusion, use of aspirin associates with a trend toward longer primary unassisted patency of newly placed hemodialysis grafts similar to that observed for ERDP/ASA.

Stent-grafts for Transjugular Intrahepatic Portosystemic Shunt Creation: Specialized TIPS Stent-graft versus Generic Stent-graft/Bare Stent Combination

To compare functional and anatomic outcomes of transjugular intrahepatic portosystemic shunts (TIPSs) created with the specialized Viatorr stent versus a Wallstent/Fluency stent combination. Retrospective review of patients who underwent TIPS creation with stent-grafts was conducted over a 54-month period ending in June 2008. Patients were divided into three groups: Viatorr only, Fluency only, and combined Viatorr/Fluency, the latter of which was included in the overall evaluation but excluded from the comparative analysis between the Viatorr and Fluency groups. Patient demographics, Child-Pugh scores, and portosystemic gradient (PSG) reduction were compared. Patencies were calculated using the Kaplan-Meier method and compared. A total of 126 TIPSs created with stent-grafts were found: 28 with Fluency stents, 93 with Viatorr devices, and five combined. No significance in demographic factors or PSGs was found among groups (P > .05). Major encephalopathy rates were 3.6% and 4.3% in the Fluency and Viatorr groups, respectively (P = 1.000). Hemodynamic success rates were 93% and 98% in the Fluency and Viatorr groups, respectively (P = .099). The primary unassisted patency rates at 6, 9, and 12 months were 87%, 81%, and 81%, respectively, in the Fluency group and 95%, 93%, and 89%, respectively, in the Viatorr group (P = .03). Portal and hepatic end stenoses were the causes of TIPS narrowing in the Fluency and Viatorr groups, respectively. The Wallstent/Fluency stent combination is associated with a 1-year patency rate greater than 80%, with no significant difference versus the Viatorr stent regarding technical and hemodynamic success and encephalopathy rate. However, the Viatorr stent is associated with improved patency (89%) versus this bare stent/stent-graft combination.

The middle-arm fistula as a valuable surgical approach in patients with end-stage renal disease

American and European guidelines recommend the distal radial-cephalic fistula (dRCF) as the first and best hemodialysis access in patients with end-stage renal disease (ESRD). However, this kind of arteriovenous fistula (AVF) shows a limited primary unassisted patency and frequently needs surgical revisions or angiographic procedures, or both. When dRCF is not feasible, guidelines suggest a proximal brachiocephalic AVF. The middle-arm fistula (MAF), or autogenous forearm radial-median direct access, has been suggested as a possible alternative approach. This study evaluated MAF primary unassisted patency, the most frequent causes of MAF failure, and the possible related factors. Data on patients with a MAF placed from January 1991 until June 2008 were retrospectively collected. The probability of MAF failure overall and by the main subgroups was estimated according to Kaplan-Meier with Greenwood standard error (SE). Comparison of failure among different subgroups was performed using the log rank test in univariate analyses. The Cox regression model was used to investigate factors that independently affected the overall hazard of failure and cause-specific hazard of thrombosis. At the end of follow-up, 14.0% of MAF failed (11.6% thrombosis, 1.7% stenosis, 0.7% failed maturation), and 44.2% of MAF were still working. Cumulative probability of MAF unassisted primary patency after 4 years from the creation was 79%. Univariate analyses highlighted that women (P = .019), underweight patients (P = .010), and MAF implantation after starting hemodialysis (P < .001) had a higher risk of MAF failure for any cause than men, normal and overweight patients, and MAF implanted before starting hemodialysis. Results of the Cox multivariate analysis for overall MAF failure confirmed that only MAF implantation before starting hemodialysis is a protective factor against any failure (P = .003), whereas female gender (P = .016) was associated with an increase of the thrombosis hazard ratio to 2.04 (95% confidence interval, 1.14-3.63). Our data demonstrate that MAF has a good unassisted primary patency and suggest that this kind of AVF could be a valuable alternative surgical approach when dRCF is not feasible in ESRD patients.

Functional Polymorphisms in Matrix Metalloproteinases-1, -3, -9 are Associated with Arteriovenous Fistula Patency in Hemodialysis Patients

Matrix metalloproteinases (MMPs) are risk factors for cardiovascular diseases. This study evaluated the association of genotype polymorphisms of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in hemodialysis (HD) patients with arteriovenous fistula (AVF) failure. Genotype polymorphism of MMP-1, MMP-2, MMP-3, and MMP-9 and TIMP-1 and TIMP-2 and clinical and laboratory parameters were compared between Chinese HD patients with (n = 170) and without (n = 426) AVF failure. Significant associations were found between AVF failure and the following factors (hazard ratio): longer HD duration (1.007 per month), lower pump flow (0.991 per ml/min), higher dynamic venous pressure (1.016 per mmHg), location of AVF on right side (1.630 versus left side) and upper arm (2.385 versus forearm), history of cardiovascular disease (1.656 versus absence of history), 1G/1G genotype of MMP-1 -1607 1G >2G SNP (2.315 versus 1G/2G + 2G/2G genotypes), 6A/6A genotype of MMP-3 -1612 5A >6A SNP (1.712 versus 5A/6A + 5A/5A), and C/C genotype of MMP-9 -1562 C>T SNP (1.650 versus C/T+T/T). The positive predictive rates for AVF failure were 63.0% and 6.7% for patients with the highest-risk (1G1G/6A6A/CC) and lowest-risk (2G2G or 2G1G/5A5A or 6A6A/TT or TC) composite MMP-1/MMP-3/MMP-9 genotype, respectively. The unassisted patency of AVF at 5 years decreased significantly from 93.3% to 38.4% for the composite MMP-1/MMP-3/MMP-9 genotypes (lowest versus highest risk, P < 0.001). Specific genotypes of MMP-1, MMP-3 and MMP-9 with lower transcriptional activity are associated with higher frequencies of AVF failure, which may result from more accumulation of extracellular matrix, leading to AVF stenosis.

Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients for Management of Refractory Ascites: Clinical Outcome

To determine the effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) creation in liver transplant recipients with recurrent portal hypertension presenting with refractory ascites. A retrospective review of transplant recipients undergoing TIPS creation was performed over a 6-year period. Recipients were noted for age, sex, TIPS indication, Model for End-stage Liver Disease (MELD) score, cause of initial liver disease, and time between first transplantation and TIPS creation. Clinical success was defined as graft survival of longer than 1 month with improvement in ascites. New-onset or worsening encephalopathy was noted. Graft survival and patency were calculated according to the Kaplan-Meier method. MELD score and portosystemic gradient (PSG) before and after TIPS creation were evaluated for prediction of graft loss less than 3 months after TIPS creation. Nineteen liver transplant recipients underwent TIPS creation for ascites. Mean time from transplantation was 3.5 years (range, 3.7-112.2 months). Mean MELD score before TIPS creation was 17 (range, 7-24). The technical, hemodynamic, and clinical success rates were 100%, 95%, and 16%, respectively. Encephalopathy developed in five patients (26%). Thirty- and 90-day mortality rates were 16% (n = 3) and 21% (n = 4), respectively. Primary unassisted patency and graft survival rates at 1, 3, and 6 months were 100%, 90%, and 90% and 79%, 58%, and 47%, respectively. MELD score parameters were significant indicators (P < .05) for graft survival beyond 3 months, but PSG parameters were not. TIPS for the management of ascites in liver transplant recipients is not as clinically effective as it is in patients with native livers (16% vs 50%-80% in the literature). MELD score is a predictor of graft survival; PSG parameters are not.

Effect of Dipyridamole Plus Aspirin on Hemodialysis Graft Patency

Conclusion: Use of the combination of dipyridamole plus aspirin reduces risk of stenosis and improves duration of primary unassisted patency of newly created arteriovenous grafts. Summary: Arteriovenous grafts remain a common source for dialysis access. Although it is generally possible to restore patency to arteriovenous grafts after thrombosis, such procedures are costly. The annual cost of procedures related to vascular access is estimated to exceed $1 billion in the United States (US Renal Data System. 2007 Annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2007). It is postulated that because dipyridamole acts by inhibiting the proliferation of vascular smooth muscle cells and that its use in treatment of patients with newly created hemodialysis access may improve patency of the dialysis access graft. The authors therefore performed a randomized, double-blind, placebo-controlled trial to determine whether extended-release dipyridamole plus aspirin inhibited stenosis of vascular access and prolonged primary unassisted patency of newly created dialysis access grafts. Patients were randomized to receive dipyridamole at a dose of 200 mg and aspirin at a dose of 25 mg twice daily, or placebo, after placement of a new arteriovenous dialysis access graft. The primary outcome was loss of primary unassisted patency of the access graft. Secondary outcomes included cumulative graft failure and death. Thirteen centers in the United States participated in the study, and 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients). The study extended for 4.5 years, with an additional 6 months of follow-up. Blood flow rates at access sites were measured each month after the patient started on hemodialysis. Measurements were done using ultrasound-indicated dilution techniques. Baseline characteristics of the two study groups were similar, as were graft blood flow rates at the time of baseline measurement. Of the grafts placed, 94% were expanded polytetrafluoroethylene, and 5% were made from some other synthetic materials. Twenty-nine percent of the grafts were forearm grafts and 44% were in the upper arm, with 6% in the leg. The rate of adherence to the study medication regimen was 83% in both groups. At 1 year, primary unassisted patency was 23% (95% confidence interval [CI], 18%-28%) in the placebo group and 28% (95% CI, 23%-35%) in the dipyridamole-aspirin group. Adjusting for prespecified factors, the hazard ratio (HR) for loss of primary unassisted graft patency in the dipyridamole plus aspirin group compared with the placebo group was 0.82 (95% CI, 0.68-0.98; P = .03). This provided a relative reduction in the rate of loss of primary unassisted graft patency of 18%. The HR for loss of primary unassisted graft patency in the dipyridamole-aspirin group compared with the placebo group was 0.76 (95% CI, 0.60-0.96; P = .02) among patients not receiving aspirin at baseline and 0.92 (95% CI, 0.68-1.24; P = .57) among those receiving aspirin at baseline. There was an overall 28% reduction in rate of stenosis of >50% from treatment with dipyridamole plus aspirin (HR, 0.72; 95% CI, 0.57-0.90; P = .005). Mean duration of primary patency was 5.8 months (95% CI, 4.3-7.1) in the extended-release dipyridamole-aspirin group and 4.3 months (95% CI, 3.6-5.4) in the placebo group. Comment: The data indicate that the combination of extended release dipyridamole plus aspirin in patients who had not previously received aspirin therapy had a statistically significant effect on extending primary patency of hemodialysis access grafts. The effect was modest and not clinically important. The aspirin and dipyridamole combination delayed by 6 weeks the median time to loss of primary patency in patients with newly created arteriovenous grafts. Put another way, the drug combination provides a reduction in the number of patients with primary graft failure by one patient for every 20 patients treated for 1 year. Because treatment with dipyridamole plus aspirin can cost between $5000 and $2200 per year, it is unclear if this therapy is cost-effective. The importance of this study is that it indicates that pharmacologic therapy targeting intimal hyperplasia potentially can improve the patency of dialysis access grafts. However, a better, more robust, effect will be needed to change practice.

Effect of Dipyridamole plus Aspirin on Hemodialysis Graft Patency

Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity. We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates. At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups. Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)

Arteriovenous Fistula Patency Associated with Angiotensin-Converting Enzyme I/D Polymorphism and ACE Inhibition or AT1 Receptor Blockade

Background: Compromise of arteriovenous fistula (AVF) patency is caused by venous intimal hyperplasia. Many studies indicated that the renin-angiotensin-aldosterone system plays an important role in the development of intimal hyperplasia. Here we determined whether angiotensin-converting enzyme (ACE) I/D polymorphism is an independent prognostic factor for AVF patency in hemodialysis (HD) patients. Methods: One hundred and fifty-five HD patients with native AVF were enrolled and genotyped, retrospectively. The primary end point was unassisted patency of the AVF, which was defined as the time from the first fistula surgery to the AVF failure. Results: The unassisted AVF patency at 58 months was 47.0% in the DD genotype group and 71.8/82.9% in ID/II groups (p < 0.01). ACE inhibitors (ACEI) or angiotensin II receptor blockers (ARB) intake had significant impact on AVF patency in the ACE DD group (p = 0.03). Using a Cox-adjusted model, we observed a significant correlation between the increase in the incidence of AVF failure and diabetic nephropathy, higher mean serum phosphorus level, and the ACE DD genotype. Conclusion: The ACE I/D polymorphism was associated with the development of AVF failure, and a preventive role of ACEI or ARB intake on AVF patency in ACE DD patients was observed.

Salvage of Nonmaturing Native Fistulas by Using Angioplasty

To retrospectively review outcomes following angioplasty of nonmaturing autogenous hemodialysis fistulas. Institutional review board exemption was received for this HIPAA-compliant retrospective study; informed consent was waived. During 48 months, 101 patients underwent fistulography for percutaneous salvage of nonmaturing native fistulas. Clinical and technical success, need for secondary interventions, and complications were recorded according to consensus definitions. Patency following angioplasty was estimated with the Kaplan-Meier technique. Patient age, sex, ethnicity, fistula age, fistula type, number of stenoses, maximal angioplastic balloon diameter used, and presence of palpable thrill following angioplasty were examined as predictors of primary patency of the fistula following intervention by using Cox proportional hazards model. Mean patient age was 58 years; 35% were women. Median time from fistula creation to fistulography was 2.5 months. Hemodynamically significant (>50%) stenoses were identified in 88% (89 of 101) of patients; angioplasty was attempted in 96% (85 of 89). Technical success was achieved in 92% (78 of 85) of fistulas following angioplasty; clinical success of normal hemodialysis with total access blood flow of more than 500 mL/min occurred following 88% (75 of 85) of angioplastic interventions. No major and two minor complications occurred. Mean primary unassisted patency at 3, 6, and 12 months was 60%+/-6% (95% confidence interval), 45%+/-6%, and 34%+/-6%, respectively. Additional angioplasty (n=12), stent placement (n=1), or thrombectomy (n=1) during subsequent interventions resulted in mean secondary patency at 3, 6, and 12 months of 82%+/-4%, 79%+/-5%, and 75%+/-6%, respectively. Patients without thrill following angioplasty were more than twice as likely to lose patency as patients with thrill (P=.035). No relationship was seen between primary patency and other predictors examined. Early fistulography enables identification of underlying areas of stenosis in nonmaturing fistulas, which can be safely and effectively treated with angioplasty. With continued surveillance and repeat interventions, functional patency can be sustained in the majority of fistulas.