Dr. Lee and Dr. Tindni contributed equally to this manuscript and are designated co-first authors.
Improved Cumulative Survival in Fistulas Requiring Surgical Interventions to Promote Fistula Maturation Compared with Endovascular Interventions
Article first published online: 9 MAR 2012
© 2012 Wiley Periodicals, Inc.
Seminars in Dialysis
Volume 26, Issue 1, pages 85–89, January/February 2013
How to Cite
Lee, T., Tindni, A. and Roy-Chaudhury, P. (2013), Improved Cumulative Survival in Fistulas Requiring Surgical Interventions to Promote Fistula Maturation Compared with Endovascular Interventions. Seminars in Dialysis, 26: 85–89. doi: 10.1111/j.1525-139X.2012.01060.x
- Issue published online: 24 JAN 2013
- Article first published online: 9 MAR 2012
Due to high nonmaturation rates, arteriovenous fistulas (AVF) frequently require intervention(s) to promote maturation. Endovascular or surgical interventions are often undertaken to salvage nonmaturing AVFs. The objective of this study was to compare the impact of surgical versus endovascular interventions to promote AVF maturation on cumulative AVF survival.
We evaluated 89 patients with new AVF placement from a Veterans Affairs population over a 5-year period. Of these, 46 (52%) required intervention(s) to achieve successful maturation for dialysis: 31 patients had surgical revisions and 15 patients had endovascular repairs. We compared cumulative survival between AVFs requiring no intervention, surgical revision, and endovascular intervention to promote AVF maturation.
Cumulative survival was longer in AVFs receiving surgical intervention compared with angioplasty to promote AVF maturation (p = 0.05). One-year cumulative survival was 86% vs. 83% vs. 40% for no intervention vs. surgery vs. angioplasty, respectively.
In AVFs that required interventions to promote maturation, AVFs with surgical intervention had longer cumulative survival compared with those AVFs with endovascular intervention. AVFs with surgical intervention to promote maturation had similar 1-year cumulative survival to those AVFs that did not require intervention to promote maturation.
Arteriovenous fistulas that fail to mature, due to either early thrombosis or failure (1–3), remains the major obstacle to increasing the proportion of dialysis patients with AVFs in the United States. Consequently, we have seen a major effort to aggressively treat and salvage nondeveloping AVFs to improve AVF maturation outcomes (4–10). Both surgical revision and endovascular repair have been established options for treatment of stenoses in AVFs, with most publications focusing on interventions in previously functioning AVFs, and primary patency the main outcome assessed (11–16). However, there are few comparative studies evaluating surgery vs. endovascular treatment to salvage nonmaturing AVFs. To answer this question, we compared the cumulative survival among AVFs requiring surgical vs. endovascular interventions to promote maturation.
A vascular access database from the Cincinnati Veterans Affairs (VA) Medical Center, maintained by a dedicated vascular access coordinator, was queried to identify prevalent hemodialysis patients requiring a new AVF placement from 2005 to 2010. All patients were under the care of attending VA nephrologists. During this same period, all vascular accesses were created by two dedicated vascular access surgeons with subsequent vascular access surgical revisions or endovascular interventions performed by the same vascular access surgeons or by interventional radiologists.
Vascular Access Management
Preoperative ultrasound mapping was performed on all patients prior to AVF placement with a minimum threshold of 2.5 mm for the vein and 2.0 mm for the artery used to determine creation of an AVF (17). Patients were evaluated by the surgeon in clinic 4–6 weeks after creation of an AVF. If there was an abnormality detected on physical examination by the surgeon, the patient had corrective procedures performed either by the surgeon or was referred to interventional radiology. These procedures could include endovascular (angioplasty) or surgical revisions to the AVF. The decision to refer for surgery vs. endovascular intervention was based primarily on first availability for operating room time or interventional radiology services. During the study period, interventional radiology services at the Cincinnati VA were available only once a week. In our VA patient population, AVFs are typically allowed to mature for 2–3 months before initial cannulation, and permission for initial AVF cannulation is given by the vascular access surgeon or vascular access coordinator, who is an experienced dialysis nurse.
Data Collection and Analysis
Information related to access history, surgeries, procedures, and outcomes were collected from the vascular access database. The vascular access database included information about vascular access placements and subsequent surgical or endovascular procedures. Demographic information was obtained from the VA Computerized Medical Records System (CPRS).
From the vascular access database, we identified a comprehensive list of AVFs placed in prevalent hemodialysis patients from 2005 to 2010. We identified 89 patients who had new AVFs placed and were on hemodialysis during this study period. Cumulative access survival was calculated from the time of access creation to permanent failure. The clinical outcome of each AVF was determined from the database.
Demographic and clinical information was collected for each patient including race, presence or absence of diabetes, peripheral vascular disease (PVD), coronary artery disease (CAD), and age. Institutional Review Board approval from the University of Cincinnati and Cincinnati VA Medical Center Research and Development Committee was obtained prior to initiation of this study.
Data were reported as percentages and means ± SE, as appropriate. The clinical characteristics were analyzed using contingency table analysis, analysis of variance (ANOVA), and Student’s t-tests. A p-value <0.05 was considered statistically significant. Cumulative access survival was plotted using Kaplan–Meier survival techniques with patients censored for death, kidney transplant, or end-of follow-up, and the log-rank test used to compare the survival between patient groups. A p-value <0.05 was considered statistically significant. AVFs with primary failures were considered to have survival of 0 days because they were never useable for dialysis. There were 21 primary failures in total: five in surgery group, seven in angioplasty group, and nine in the group with no intervention. For the analysis comparing cumulative survival between angioplasty and surgical interventions, those patients who had both surgical and angioplasty procedures to promote AVF maturation (five patients in total) were placed in the angioplasty group for the purposes of the survival analysis. We believe that on a biological level, that the vasculature of patients who received both procedures will probably behave more similarly to those with endovascular intervention because of endothelial injury that occurs from balloon angioplasty. All statistical analyses were performed using the JMP® 8.0 (Cary, NC) statistical software package.
Table 1 summarizes the demographic and clinical characteristics of the patient population by type of intervention before maturation or no intervention. The angioplasty group appeared to be a more complex group with a greater proportion of diabetes and PVD, and also a trend towards more CAD. Age or race did not differ by type of intervention before maturation. Perhaps more importantly, approximately 72% of patients in all 3 groups had an AVF at the wrist.
|No intervention||Surgery||Angioplasty||p value|
|Patients (n = 89)||43 (48%)||31 (35%)||15 (17%)|
|Age||67.4 ± 1.8||61.9 ± 2.1||64.9 ± 3.0||0.14|
|White||25 (58%)||21 (68%)||7 (47%)||0.38|
|Black||18 (42%)||10 (32%)||8 (53%)|
|Yes||26 (60%)||16 (52%)||14 (93%)||0.009|
|No||17 (40%)||15 (48%)||1 (7%)|
|Coronary artery disease|
|Yes||29 (67%)||20 (65%)||14 (93%)||0.06|
|No||14 (33%)||11 (35%)||1 (7%)|
|Peripheral vascular disease|
|Yes||17 (40%)||6 (19%)||10 (67%)||0.006|
|No||26 (60%)||25 (81%)||5 (33%)|
|Location of access|
|Upper ARM||11 (26%)||10 (32%)||4 (27%)||0.81|
|Forearm||32 (74%)||21 (68%)||11 (73%)|
Types of Interventions
In total, there were 46 total interventions performed to promote AVF maturation (31 surgical and 15 endovascular). Among the 31 surgical interventions, there were 8 corrections of accessory veins, 4 conversions to upper arm AVF, 1 interposition graft placement, 2 transpositions, and 16 proximalization of the anastomosis. Among the 15 endovascular interventions, there were nine angioplasties for juxta-anastomotic lesions and six angioplasties for venous stenosis, but nonjuxta-anastomotic lesions.
Cumulative Access Survival
Among the 89 patients with new AVF placement, 46 (52%) AVFs required interventions to promote maturation: 31 patients had surgical revisions and 15 patients had endovascular repairs. AVFs with no interventions or surgical interventions had better cumulative survival compared with those AVFs requiring angioplasty (p = 0.03) (Fig. 1). Cumulative survival was longer in AVFs requiring surgical repair compared with angioplasty to promote AVF maturation (p = 0.05). One-year cumulative survival was 86% vs. 83% vs. 40% for no intervention vs. surgery vs. angioplasty groups, respectively.
Recent studies have shown high rates of nonmaturing AVFs, as high as 60% in a recently published, large, multicenter, randomized clinical trial (1). Nonmaturing AVFs frequently have identifiable anatomic abnormalities, most commonly peri-anastomotic stenoses, which can be identified by physical examination (18–20) and/or angiography (7,8,10). Targeted endovascular or surgical interventions to repair these abnormalities are often successful in salvaging nonmaturing AVFs, making them suitable for dialysis (7–9,21–23). However, formal comparative studies directly evaluating these two methods in salvaging nonmaturing AVFs are lacking.
The few published studies directly comparing surgical vs. endovascular outcomes to treat stenotic or thrombotic AVFs have primarily focused on AVFs that were previously functional for dialysis use (11,16), and these studies have measured primary patency or restenosis rates. Ito et al. recently reported that the primary patency rates were significantly lower in endovascular repair of stenotic AVF vs. surgical repair (16). Furthermore, Tessitore et al. have reported that the restenosis rate was 2.77 times higher after endovascular vs. surgical intervention after preemptive repair of juxta-anastomotic stenosis in forearm AVFs (11). There have been only two studies comparing AVF outcomes by the type of intervention to salvage nonmaturing AVFs (13,24). The first study by Long et al. compared outcomes between surgical and endovascular interventions to treat nonmaturing AVFs and reported a 1-year primary patency of 71% vs. 41% for surgery vs. angioplasty (p < 0.02), respectively (13). The second study by Lee et al. reported no difference in cumulative survival in AVFs by type of intervention to promote AVF maturation (p = 0.8298) (24). Our current study compares the long-term outcome between endovascular interventions and surgical repair in nonmaturing AVFs requiring intervention to promote maturation, and observed significantly longer cumulative AVF survival in AVFs that had surgical repair compared with endovascular intervention. Moreover, cumulative AVF survival in those AVFs requiring surgical repair to promote AVF maturation was very similar to those AVFs not requiring intervention to promote maturation.
Why might endovascular interventions to promote AVF maturation be associated with shortened cumulative AVF survival compared with surgical repair? The most likely explanation is that these endovascular procedures induce endothelial injury that leads to more aggressive neointimal hyperplasia development, rapid re-stenosis, which eventually leads to AVF failure. In support of this hypothesis, Chang et al. observed histologically that re-stenotic lesions in AVFs after endovascular interventions had greater cellular proliferation activity within the intima and media, as compared with AVFs with primary stenosis (25). Furthermore, in experimental cardiovascular models of vascular injury following angioplasty, a progressive development of inflammation, granulation, extracellular matrix remodeling, smooth muscle cell proliferation and migration occurs, leading to neointimal thickening and restenosis, as well as the inability of the vessels to adequately remodel after injury (26–29). In contrast, surgical repair, specifically, creation of a neo-anastomosis, may result in less endothelial perturbation and damage, and consequently have a better long-term survival. Furthermore, our results suggest that surgical repair of nonmaturing AVFs may have similar cumulative survival compared with those AVFs not requiring any intervention for maturation, probably because of less endothelial damage that occurs during the surgical revision.
In the United States, endovascular intervention has now replaced surgical therapy as the standard management of vascular access dysfunction, in part due to ease and efficiency of scheduling, and minimal invasiveness of the procedure compared with surgery. USRDS data from 2009 shows that angioplasties to treat AVF dysfunction have increased threefold from 1998 to 2007 (30). Furthermore, recently, endovascular interventions have expanded to include “balloon-assisted maturation” (BAM) for AVF maturation. BAM has been reported in several publications as a routine procedure to promote AVF maturation in nonmaturing AVFs (31,32) and to dilate vessels even prior to AVF creation (33). Until novel and locally delivered therapies are developed to better treat the endothelial injury that occurs as the result of angioplasty, endovascular interventions to treat AVF stenosis will probably continue to be plagued by poor primary patency and cumulative survival compared with surgery (11–13). However, at the present time, there are no effective pharmacologic treatments to treat AVF nonmaturation, largely due to our limited understanding of the pathophysiology of AVF maturation (5,34–38), so the standard approach to salvaging nonmaturing AVF will remain the performance of endovascular or surgical interventions. Thus, a major future question is what the ideal approach to treat nonmaturing AVFs should be, surgery or endovascular, particularly in distal AVFs with juxta-anastomotic venous lesions, to achieve the best AVF outcomes. As the data from published observational studies directly comparing treatment (endovascular vs. surgery) for stenotic and nonmaturing AVFs with short- and long-term AVF outcomes have been inconclusive (but may favor better outcomes with surgical intervention) (11–13), this question can only be answered with a well-designed, randomized-controlled trial.
Our present study does have some limitations. First, this was a single-center study at a VA medical center, so the results may not be generalizable to all nephrology practices. Second, because our study sample was from VA population, all AVFs created were in males. Therefore, these results may not be generalizable to females, where previous reports have shown females to have lower prevalence of AVFs and smaller vessel sizes (4,39). Finally, this was a retrospective study, so there may have been undocumented differences in AVFs which received surgical vs. endovascular interventions, other than availability of surgical operating time or interventional services as described in the methods section.
Our results suggest that endovascular interventions to promote AVF maturation may be associated with shorter cumulative AVF survival compared with surgical repair. Furthermore, our results (a) emphasize the importance of further research evaluating the mechanisms of injury following AVF interventions to promote maturation and (b) underscore the urgent need for a randomized-controlled trial that compares surgical vs. endovascular interventions to treat nonmaturing AVFs.
Acknowledgments Dr. Lee is supported by NIH 5K23DK083528-02 and National Kidney Foundation Franklin McDonald/Fresenius Medical Care Young Investigator Clinical Research Award. Dr. Roy-Chaudhury is supported by NIH 5U01-DK82218, NIH 5U01-DK82218S (ARRA), NIH 5R01-EB004527, NIH 1R21-DK089280-01, a VA Merit Review, two University of Cincinnati NIH/NCCR UL1RR026314 CTSA grants, and industry grants.
Conflict of Interest None declared.
Disclosures Dr. Lee is a consultant for Proteon Therapeutics. Dr. Roy-Chaudhury is on the advisory board/consultant for Pervasis Therapeutics, Inc., Proteon Therapeutics, WL Gore, Bioconnect Systems, Philometron, and NanoVasc, and receives research support from BioConnect Systems, Shire, Proteon Therapeutics, and WL Gore. These funding sources had no involvement in the design or execution of this study.
- 13Management of perianastomotic stenosis of direct wrist autogenous radial-cephalic arteriovenous accesses for dialysis. ****Journal of Vascular Surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 53:108–114, 2011, , , , , , , , :
- 30U.S. Renal Data System, USRDS 2009 Annual Data Report: Atlas of CKD and ESRD in the United States, National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, 2009.