A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis.

OBJECTIVE: Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. METHODS: PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. RESULTS: The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use. CONCLUSIONS: Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.

PATENCY-2 trial of vonapanitase to promote radiocephalic fistula use for hemodialysis and secondary patency.

OBJECTIVE: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. METHODS: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. RESULTS: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, (p = 0.33). The Kaplan-Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73-82) for vonapanitase and 76% (95% CI, 70-82) for placebo (p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo (p = 0.054). The Kaplan-Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44-55) for vonapanitase and 43% (95% CI, 35-50) for placebo (p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. CONCLUSIONS: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 (https://clinicaltrials.gov/ct2/show/NCT02414841).

Outcomes of arteriovenous fistulae created by a U.S. interventional nephrologist.

Arteriovenous fistulae (AVF) outcomes in the United States continue to fall short of expectations and continue to compare disfavorably to European AVF outcomes. This study presents the early experience of nephrologist created AVF outcomes in the U.S. hemodialysis population. A retrospective analysis of a prospectively collected vascular access database was performed. All patients who were referred for vascular access placement over a 1-year period were eligible for inclusion. One hundred five (n = 105) patients were initially included in the database. An AVF was placed in 100% of patients referred for vascular access. Two complications were identified (one steal syndrome and one infection) for a rate of 1.9%. The patient demographics included 38.7% female, age 63.6 + or - 14.8, 50.0% diabetic, 66.0% hypertensive, with 65.1% of patients in stage 5 chronic kidney disease at the time of AVF placement. Average target artery diameter was 4.09 + or - 1.16 mm while average target vein diameter was 3.66 + or - 1.20. Twenty-one AVF were placed in the forearm (19.8%) with the remainder being placed in the upper arm vessels. Eighteen patients (18.56%) failed to mature at 6 weeks. Sixty-four patients (65.98%) required revision or intervention of their AVF between 12 weeks postoperatively and the endpoint of the study. Eighty patients (84.21%) had patent AVF at an average follow-up of 286.2 + or - 98.14 days. No identifiable risk factors among those listed above were associated with a significant impact on AVF outcomes. AVF outcomes that compare favorably to those of Europe can be achieved by U.S. interventional nephrologists. Furthermore, the dictum that distal is better needs to be re-examined if the United States hopes to achieve the goal of 66% AVF prevalence.

Arteriovenous Fistula Creation by Nephrologist Access Surgeons Worldwide.

Several years ago, we published an article in this journal entitled "Autologous Arteriovenous Fistula Creation by Nephrologists." The goal of that effort was to review outcomes published by nephrologist access surgeons from around the world. An attempt was also made to define the elements that were necessary for successful autologous fistula creation in hopes that they might be used by others in an effort to increase the number of and durability of autologous fistulas in the dialysis population. Our goal, here, is to update the previous information based on recently published literature to better understand the role that nephrologist access surgeons play in the care of our dialysis patients worldwide.

Autologous arteriovenous fistula creation by nephrologists.

In 1966, physicians from the Bronx Veterans Administration Hospital, New York City described the surgical creation of a distal radial artery to cephalic vein AV fistula. This novel configuration, for the first time, allowed effective and reproducible cannulation for hemodialysis access and has remained the gold standard for hemodialysis access since. More than 40 years later, vascular access remains the Achilles' heel of hemodialysis therapy. In this article, we will review the outcomes and techniques of the pre-eminent nephrologist-surgeons from around the world in an attempt to define those elements that are necessary for successful autologous fistula creation. The hope is that these elements may be employed by others in an effort to increase the numbers and durability of autologous fistulae in incident and prevalent hemodialysis patients, particularly in the United States.

Role of surgical intervention for cephalic arch stenosis in the "fistula first" era.

Cephalic arch stenosis (CAS) is a frequent cause of vascular access dysfunction in patients with brachiocephalic fistulae. While percutaneous balloon angioplasty has been used to treat CAS, the results of this approach have been poor due to multiple factors including resistant nature of the stenosis, development of early restenosis, as well as poor patency and high vein rupture rates. In this analysis, we report the results of an alternative approach to manage this problem. Thirteen patients with frequently recurring CAS were referred for surgical intervention. Angiographic images recorded during the prior percutaneous procedures were made available to the surgeons. The surgical procedure entailed transecting the healthy portion of the cephalic vein distal to the stenotic segment in the arch, transposing and anastomosing it to the upper basilic/axillary vein. Following surgical revision, development of access dysfunction was treated with percutaneous balloon angioplasty. Patency rates for angioplasty before and after the surgical revision were evaluated. Primary patency rates for angioplasty before the surgical revision were 23%, 8% and 0% at 3, 6, and 12 months, respectively. Following surgical revision, all patients needed angioplasty procedure. However, primary patency increased to 92%, 69%, and 39% at 3, 6, and 12 months, respectively (p = 0.0001). Secondary patency before the surgical revision at 3, 6, and 12 months was 100%, 39%, and 8%, respectively, compared with 92% at 3, 6, and 12 months postsurgical revision (p = 0.0003). The results of this study demonstrate that surgical transposition of the cephalic vein in frequently recurring CAS is a viable option and yields better patency rates for future angioplasty procedures.

Efficiency and outcomes of emergent vascular access procedures performed at a dedicated outpatient vascular access center.

The outpatient vascular access center (VAC) may have an important impact in improving the outcomes of emergent procedures on nonfunctioning hemodialysis access. An emergent procedure is defined as the absence of a functioning access for hemodialysis, including thrombosed graft or fistula, nonfunctioning dialysis catheters, and the need for access to initiate emergent hemodialysis. The aim of this study was to prospectively evaluate the efficiency and outcomes of all consecutive emergent hemodialysis access procedures during a 3-month period at a single high volume VAC. Data collection for each procedure included anatomic outcome, clinical outcome, the amount of time from referral to procedure and to successful dialysis, 2-week-follow-up to screen for postprocedure complications and fluoroscopy time. A total of 157 emergent procedures were performed in 136 patients with the majority of interventions on nonfunctioning grafts and tunneled catheters. The overall clinical success (defined as successful postprocedure completion of at least one dialysis treatment at the prescribed blood flow) was achieved in 149 out of 157 (95%) cases. 90% of subjects completed their procedure within 24 hours of the initial referral to the VAC. The study also demonstrated a rapid turn around time, with successful dialysis being performed within 24 hours of referral in 61% and within 48 hours in 90% of referrals. This is the first study to demonstrate both the efficiency and successful outcomes of an outpatient vascular access center in treating emergent vascular access problems.

Pharmacomechanical thrombolysis of natural vein fistulas: reduced dose of TPA and long-term follow-up.

Twenty-five episodes of pharmacomechanical thrombolysis of 20 clotted arteriovenous fistulas (AVFs) are reported. The technique presented utilizes the local instillation of tissue plasminogen activator (TPA) in small doses together with manual maceration to dissolve clot and balloon angioplasty to correct the underlying stenoses. Since the minimum dose of TPA necessary to successfully perform thrombolysis of a natural vein fistula had never been determined, an attempt to use as minimal a dose of TPA as possible was made. Five procedures were performed in fistulas which had previously undergone a thrombolysis procedure with TPA. The procedures were successful in 92% of cases with an average dose of TPA required of 2.3 +/- 0.32 mg/procedure. In addition to the 20 accesses in this article, we offer follow-up life table data on 15 fistulas that were previously reported for a total of 35 accesses salvaged with pharmacomechanical thrombolysis. Primary patency was 11.2 months and secondary patency was 25 months. Fifty-five percent of fistulas required repeat angioplasty procedures at an average of 3.6-month intervals. In addition, more than half of the fistulas that presented with clotting required repeat interventions for continued patency. This report demonstrates the effectiveness of small doses of TPA in successful pharmacomechanical thrombolysis of clotted fistulas.