REVIEW ARTICLES Richard P. Cambria, MD, Section Editor
The outcome of the proximal radial artery arteriovenous fistula Cong Cong Wu, MD, Hua Jiang, MD, Jun Cheng, MD, Ling Fei Zhao, MD, Kai Xiang Sheng, MD, and Jiang Hua Chen, MD, Hangzhou, China Background: Guidelines recommend placing native arteriovenous fistulas (AVFs) as far distally in the upper extremity as possible. If there are adequate veins and adequate arteries, a wrist fistula, which offers notably lower risks than grafts and catheters, would be the first choice for long-term hemodialysis. With increasing failure and difficulty to create wrist fistulas, we reviewed outcomes of the proximal radial AVF (PRAAVF) and demonstrate that it is an effective technique. Methods: A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was primary failure, primary patency rates, and secondary patency rates after 1 and 2 years. Estimates were pooled with the random effects model, and meta-regression and sensitivity analysis were performed to explore heterogeneity. Results: According to selection criteria formulated a priori, 10 articles (n [ 1310) were included and finally analyzed after screening 1687 articles. The pooled primary failure was 12.3% (95% confidence interval [CI], 7.6%-17.0%; c2 [ 70.8, I2 [ 87.3%), the primary patency, including primary failure, was 73.6% (95% CI, 52.4%-94.9%; c2 [ 71.3, I2 [ 97.2%) at 1 year and 70.5% (95% CI, 50.6%-90.5%; c2 [ 58.8, I2 [ 96.6%) at 2 years. Secondary patency was 80.0% (95% CI, 72.8%-87.2%; c2 [ 24.42, I2 [ 75.4%) at 1 year and 73.7% (95% CI, 65.2%-82.2%; c2 [ 28.51, I2 [ 79.0%) at 2 years. Individual variate meta-regression analysis found the definition of primary failure was a significant source of heterogeneity (P [ .009). Steal syndromes developed in four of 832 (0.5%) of the PRAAVFs, and venous hypertension developed in four of 284 (1.4%). Conclusions: The PRAAVF presented low to moderate primary failure and high primary and secondary patency rates with acceptable complications. Consideration of the specific fistula is required when creating a vascular access, especially when a wrist fistula has failed or is predicted to be unsuccessful. (J Vasc Surg 2015;61:802-8.)
The native arteriovenous fistula (AVF) is recommended as the best vascular access for hemodialysis by the National Kidney Foundation Kidney Dialysis Outcomes Quality Initiative (NFK/DOQI) clinical practice guideline.1 Compared with grafts and catheters, AVFs have the longest patency duration and the least interventions.2,3 Patients with AVFs have the lowest risks of death, infections, and cardiovascular events4 and also the lowest costs to the health care system.3 The NFK/DOQI suggests an order of preference for vascular access of radial artery-cephalic vein From the Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University; the Key Laboratory of Nephropathy, Zhejiang Province; and the Kidney Disease Immunology Laboratory, The Third Grade Laboratory, State Administration of Traditional Chinese Medicine of PR China. This study was supported by funding from Key Projects in the National Science & Technology Pillar Program in the Twelfth Five-Year Plan Period (No. 2011BAI60B07). Author conflict of interest: none. Reprint requests: Jiang Hua Chen, MD, Zhejiang University, Kidney Disease Center, College of Medicine, 79 Qingchun Rd, Hangzhou 310003, China (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2015 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2014.08.112
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AVF at the wrist, brachial artery-cephalic vein AVF in the upper arm, a transposed brachial artery-basilic vein AVF, or an arteriovenous graft. Catheters are discouraged as permanent vascular accesses.1 However, failure of AVFs created at the wrist and difficulty in maintaining patency seem to have increased in recent years because of the poor quality of distal veins and arteries, frequently owing to previous venous catheters, diabetes mellitus, peripheral vascular disease, and older age.3,5,6 Meanwhile, the brachial AVF has a higher risk of distal steal syndrome, arm ischemia, high-output heart failure,7 and right ventricular dysfunction8 than the wrist fistula. A suitable alternative to avoid the upper arm AVF is a fistula created in the proximal forearm, which was first described in 1977 by Toledo-Pereyra et al9 and Gracz et al10 as a proximal radial artery fistula. Toledo-Pereyra et al9 created the proximal radial artery fistula by connecting the proximal radial artery and the cephalic vein, whereas Gracz et al10 anastomosed the perforating branch of the median antecubital or cephalic vein end-to-side to the artery. Another choice is a middle-arm fistula reported by Bonforte et al11 in 2004, in which the proximal radial artery is anastomosed to the nearest vein (cephalic, median antebrachial, perforating vein). Previous studies9-11 have shown that fistulas using the proximal radial artery as the inflow have excellent patency rates, allowing for multiple access sites in the proximal forearm.10
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Considering the extensive public policy to promote fistula use, we performed a systemic review and pooled estimates of primary failure and 1-year and 2-year primary patency and secondary patency rates of the proximal radial artery AVF (PRAAVF). We aimed to improve the accuracy of the PRAAVF outcome estimates and explore an additional site and type of vascular access selection. METHODS Search strategy. A systemic literature search confined to all relevant published articles until January 1, 2014, about the PRAAVF was conducted in PubMed. The keywords used were proximal, radial, fistula, middle arm, cubital, forearm, and antebrachium. Bibliographies of selected articles were also searched by hand for any additional related reports. Selection criteria. Studies had to meet inclusion criteria, which were formulated a priori. Firstly, a study was eligible only if an AVFs was created with the PRA as the inflow in the forearm, irrespective of the type of anesthesia, the type of anastomosis, and the type of vein used to create the anastomosis. The median antebrachial vein, cephalic vein, perforating vein, and other veins were all eligible. Secondly, the study had to report one or more of the following outcomes: primary failure and the 1-year or 2-year primary patency and secondary patency rates. Investigations were included regardless of definitions of outcome, but most of the studies were in accordance with the Society for Vascular Surgery (SVS)/American Association of Vascular Surgery and the North American Vascular Access Consortium (NAVAC).12,13 Only articles written in English were included. We excluded studies if the PRA was used in a primary or staged transposition AVF procedure. Studies involving children or adolescents were excluded. Study definitions. Primary failure was defined as immediate vascular access failure as indicated by an access that had no appearance of or a loss of bruit or thrill #72 hours of creation (NAVAC12 definition). Early dialysis suitability failure was defined as an access that, despite radiologic or surgical intervention, could not be used successfully for dialysis by the third month after its creation (NAVAC12 definition). Late dialysis suitability failure was defined as an access that, despite radiologic or surgical intervention, could not be used successfully for dialysis by the sixth month after its creation (NAVAC12 definition). Primary patency was defined as the interval from the time of access placement until any intervention designed to maintain or re-establish patency, first occurrence to access thrombosis, or reaching a censored event (NAVAC12 and SVS13 definition). Secondary patency was defined as the interval from the time of access placement until access abandonment or achievement of a censored event, including intervening manipulations by surgical or endovascular interventions (NAVAC12 and SVS13 definition). Data extraction. We extracted information on year of publication, country, recruitment start date, sample size,
Fig 1. Flow diagram shows study eligibility and inclusion.
follow-up period, mean age, sex, proportion of diabetes mellitus, outcome definitions, primary failure, primary and secondary patency rates at 1 and 2 years, selection criteria of creating the PRAAVF, different veins anastomosed to the PRA, and complications. Most studies showed patency rates in the text, life-tables, or Kaplan-Meier curves. If the patency rate was only mentioned in a Kaplan-Meier plot, we estimated it from the curve. Statistical analysis. We calculated the estimates of primary failure and patency rates using the double arcsine transformation.14 The 95% confidence interval (CI) was calculated for each estimate with the Wilson score method.15 We performed the meta-analysis in Stata 12.0 software (StataCorp LP, College Station, Tex) with the commands metan (three variables: double-arcsine-transformed primary failure or patency rates, the lower Wilson CI, the upper Wilson CI), metareg, and metaninf. The presence of heterogeneity was assessed by the c2 test and I2 statistic. When heterogeneity was high (I2 > 75%), performing a random effects model was preferred. We further explored the sources of heterogeneity by meta-regression analysis, in which potentially relevant factors examined individually were year of publication, sample size, recruitment start date, mean age, proportion of men, proportion of diabetes mellitus, and definition of primary failure. Only factors that showed P < .05 were entered into a multiple regression model. Sensitivity analysis was conducted to investigate the specific study that might be the origin of heterogeneity. We also calculated additional pooled estimates of patency rates excluding primary failure. RESULTS Included studies We searched 1687 articles and reviewed 16. After ineligible studies were excluded, 11 (n ¼ 1422), published between 1977 and 2012, met our criteria. However, two eligible articles11,16 were published using the data from overlapping patients, so we only took into account the results from the article with larger sample. Therefore, 10 studies consisting of 1310 vascular accesses finally remained. Details of the study screening are presented in Fig 1. Study characteristics and patency rates extracted from each study are separately summarized in Table I.
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Table I. Study characteristics Study
Year
Country
No.
Recruitment start
Follow-up, months
Mean age, years
Male, %
DM, %
Toledo-Pereyra9 Bruns18 Roberts24 Jennings19 Weyde17 Kumar21 Bonforte16 Whittaker22 Bhalodia20 Capurro23
1977 2003 2005 2006 2007 2007 2010 2011 2011 2012
USA USA USA USA Poland India Italy UK UK Italy
20 73 58 134 77 320 459 58 19 92
e 1998 2003 2003 1992 1990 1991 2003 2006 2003
e e 10 11 e 54 22.8 e e 33
e 57 56 61 58 32 71.4 60 61 66
e 50.7 41.0 54.5 55.8 80.0 59.9 60.3 95.0 62.7
55.0 71.0 50.0 50.7 33.8 25.0 22.9 15.5 63.0 27.6
DM, Diabetes mellitus; UK, United Kingdom; USA, United States of America.
Fig 2. Primary failure of the proximal radial artery arteriovenous fistula (PRAAVF). Weights are from random effects analysis. Heterogeneity: c2 ¼ 70.8, I2 ¼ 87.3%. The solid squares denote the mean difference, the horizontal lines represent the 95% confidence intervals (CIs), and the diamond denotes the weighted mean difference. ES, Estimate.
Meta-analysis Primary failure. Estimates of the PRAAVF primary failure rate ranged from 1.2% to 32.9% (Fig 2), with a high degree of heterogeneity (c2 ¼ 70.8, df ¼ 9; I2 ¼ 87.3%). The random effects pooled primary failure rate of the PRAAVF was 12.3% (95% CI, 7.6%-17.0%). In individual variable meta-regression analysis exploring the sources of heterogeneity, the primary failure was higher in some studies where the definition appeared to include inferior fistulas (other fistulas except radiocephalic AVF and PRAAVF) as primary failed AVF (P ¼ .009; Table II). None of other factors showed any significant relationship with heterogeneity. In the sensitivity analysis, the pooled primary failure decreased to 10.4% (95% CI, 6.0%-14.8%) when we omitted the study17 in which the PRA was anastomosed only to the perforating vein because the superficial forearm veins were completely inadequate (Fig 3). One-year primary patency rate. Estimates of the 1year primary patency rate of the PRAAVF ranged from
Table II. Results of meta-regression analysis Primary failure
Coefficient
Year No. Mean age Male DM Recruitment start Definition of PFa
0.0044 0.0003 0.0002 0.0421 0.0292 0.0077 0.1597
95% CI 0.0042 0.0009 0.0087 0.6531 0.5293 0.0072 0.0527
to to to to to to to
0.0129 0.0002 0.0090 0.7372 0.4709 0.0226 0.2666
P .271 .229 .965 .890 .896 .260 .009
CI, Confidence interval; DM, diabetes mellitus; PF, primary failure. a Definition of primary failure appeared to include inferior fistulas as primary failed ones.
47.0% to 92.3%, with a high degree of heterogeneity (c2 ¼ 71.3, df ¼ 2; I2 ¼ 97.2%). The random effects pooled 1year primary patency rate of the PRAAVF was 73.6% (95% CI, 52.4%-94.9%) and was 85.7% (95% CI, 74.3%97.1%; c2 ¼ 34.51, I2 ¼ 94.2%) when primary failure was excluded from the calculation. Because of an insufficient
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Fig 3. Sensitivity analysis of primary failure. CI, Confidence interval.
number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. Two-year primary patency rate. The estimated 2year primary patency rate of the PRAAVF ranged from 43.1% to 86.7%, with a high degree of heterogeneity (c2 ¼ 58.8, df ¼ 2; I2 ¼ 96.6%). The random effects pooled 2year primary patency rate of the PRAAVF was 70.5% (95% CI, 50.6%-90.5%) and was 81.9% (95% CI, 70.193.8; c2 ¼ 32.42, I2 ¼ 93.8%) when primary failure was excluded. Because of an insufficient number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. One-year secondary patency rate. The estimated 1year secondary patency rate of the PRAAVF ranged from 62.6% to 91.4% (Fig 4), with a high degree of heterogeneity (c2 ¼ 24.42, df ¼ 6; I2 ¼ 75.4%). The random effects pooled 1-year secondary patency rate of the PRAAVF was 80.0% (95% CI 72.8%-87.2%) and was 95.5% (95% CI 92.6%-98.4%; c2 ¼ 10.45, I2 ¼ 42.6%) when primary failure was excluded. Because of an insufficient number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. Two-year secondary patency rate. The estimated 2year secondary patency rate of the PRAAVF ranged from 52.5% to 88.2% (Fig 5), with a high degree of heterogeneity (c2 ¼ 28.51, df ¼ 6; I2 ¼ 79.0%). The random effects pooled 2-year secondary patency rate of the PRAAVF was 73.7% (95% CI, 65.2%-82.2%) and was 87.4% (95% CI, 80.2-94.7; c2 ¼ 49.2, I2 ¼ 87.8%) when primary failure was excluded. Because of an insufficient number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. Every study mentioned that unfeasible veins or arteries, or both, in the wrist were one of selection criteria of creating the PRAAVF; however, only three18-20 articles
undertook actual measurements of the diameter and mentioned the minimal criteria as an artery diameter $2.0 mm and a vein diameter $2.5 mm. Four10,21-23 articles reported one of selection criteria to be a previously failed AVF in the wrist. Arteriosclerotic or calcified arteries and thrombosed or sclerosed veins in the wrist were deemed unsuitable to create a distal AVF in the wrist so that the PRAAVF could be a second choice.10,21-23 Roberts et al24 performed procedures to create PRAAVFs in the difficult access extremity where a wrist or upper arm brachiocephalic AVF was not possible or was predicted to fail. Weyde et al17 created the PRAAVFs in patients whose superficial forearm veins were completely occlusive or destroyed up to the cubital fossa by using the perforating vein as outflow. A more aggressive strategy was adopted by Bonforte et al,16 in which two or more factors among diabetes mellitus, atherosclerosis, obesity, neoplasm, coagulation disease, peritoneal dialysis failure, or age $65 years determined the PRAAVF as the first-choice vascular access. Different veins, such as the median antebrachial vein, cephalic vein, perforating vein, were chosen for the anastomosis to the PRA, depending on the preference or proficiency of the surgeons and the anatomic structure in the forearm. According to the study of Weyde et al,17 the perforating vein would be a good choice if use of the superficial forearm veins were not feasible. Meanwhile, the PRAAVF showed outstanding performance with few complications (Table III). Steal syndrome developed in four of 832 of the PRAAVFs (0.5%) based on eight studies. Three articles evaluated venous hypertension, which occurred in four of 284 of the PRAAVF (1.4%). DISCUSSION Generally, the vascular access has been considered to be not only the lifeline but also the Achilles’ heel of hemodialysis
806 Wu et al
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Fig 4. One-year secondary patency of the proximal radial artery arteriovenous fistula (PRAAVF). Weights are from random effects analysis. Heterogeneity: c2 ¼ 24.42, I2 ¼ 75.4%. The solid squares denote the mean difference, the horizontal lines represent the 95% confidence intervals (CIs), and the diamond denotes the weighted mean difference. ES, Estimate.
Fig 5. Two-year secondary patency of the proximal radial artery arteriovenous fistula (PRAAVF). Weights are from random effects analysis. Heterogeneity: c2 ¼ 28.51, I2 ¼ 79.0%. The solid squares denote the mean difference, the horizontal lines represent the 95% confidence intervals (CIs), and the diamond denotes the weighted mean difference. ES, Estimate.
therapy. Despite all of the progress achieved since Brescia and Cimino25 introduced the native AVF in 1966, we still face a conundrum about vascular accesses. Fistulas patency is severely compromised by maturation failure, thrombosis, and stenosis. Intimal hyperplasia is thought to be the culprit lesion pathophysiologically in fistulas failing, with some potential contributors, such as outward remodeling and vascular pathology, mediated by chronic kidney disease.26 Considering the increasing number of patients with Brescia-Cimino fistulas that previously failed or in whom fistula creation at the wrist was predicted to be unfeasible, our research found the PRAAVF is a safe and reliable
alternative. In our study, the PRAAVF showed an attractive outcome: the primary failure was 12.3%, the primary patency rates were 73.6% and 70.5% after 1 and 2 years, and the secondary patency rates were 80.0% and 73.7% after 1 and 2 years. Kumar et al21 reported the mean time to fistula maturation was 26 6 5.2 days. Meanwhile, the meta-analysis by Al-Jaishi et al27 reported that the primary failure rate was 23%, the primary patency rates were 60% and 51% after 1 and 2 years, and the secondary patency rates were 71% and 64% of mixed upper arm and lower arm AVF patency. In their subgroup analysis, the primary patency rates of the radiocephalic
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Table III. Complications mentioned in studies
Study
Year
No.
Congestive heart failure, No.
Toledo-Pereyra9 Bruns18 Roberts24 Jennings19
1977 2003 2005 2006
20 73 58 134
0 e e e
0 0 0 2
e 1 e 3
e 0 e 0
e e 0 0
Weyde17 Kumar21
2007 2007
77 320
0 e
0 0
0 e
e 20
e e
Bonforte16 Whittaker22 Bhalodia20 Capurro23 Total
2010 2011 2011 2012
459 58 19 92
e e e e 0/97
e 1 e 1 4/832
e e e e 4/284
e e e e 20/527
e e e e 0/192
Steal syndromes, No.
Venous hypertension, No.
Infections, No.
Hospitalizations related to complications, No.
AVFs in lower arm were 55% overall and 46% at 1 year (n ¼ 1145) and 2 years (n ¼ 890), and the secondary patency rates were 68% overall and 58% at 1 year (n ¼ 937) and 2 years (n ¼ 682) years, including primary failure. Lok et al28 reported that the primary failure of radiocephalic AVFs (n ¼ 231) was 11.2%, including 9.1% for brachiocephalic (n ¼ 186) and 16% for brachiobasilic (n ¼ 25) AVFs. In the Maya et al29 study, the primary failure rates were 18% and 38% separately in brachiobasilic (n ¼ 67) and brachiocephalic (n ¼ 322) AVFs. Koksoy et al30 reported primary patency rates of 87% and 81% at 1 and 3 years for brachiocephalic AVFs (n ¼ 50) and 86% and 73% for brachiobasilic AVFs (n ¼ 50). The secondary patency rates at 1 and 3 years were 87% and 70% for brachiocephalic AVFs and 88% and 71% for brachiobasilic AVFs separately. Therefore, the PRAAVF could be a feasible choice with acceptable patency rates. In addition, the PRAAVF seemed to be associated with low risk of long-term or severe complications in our current investigation. We found steal syndromes developed in 0.5% (four of 832) of the PRAAVF compared with 10% to 25% of brachial artery AVFs and 1% to 1.8% of radiocephalic AVFs.31 van Hoek at al32 also reported that a cold hand developed in 50% of patients with brachiocephalic AVFs and in 12% with radiocephalic AVFs. Meanwhile, the upper arm fistula is related to an increased risk of high-output cardiac failure as a result of high vascular access flow.7 Left ventricular disorders and volume overload may induce or aggravate pulmonary hypertension, which is a rare disease but with high mortality.33 Paneni et al8 also reported right ventricular dysfunction can emerge in patients with brachial AVFs.8 Even though guidelines suggest a brachiocephalic fistula as the second choice, we deem the PRAAVF could be an additional, even better option, than the former. Because of significant heterogeneity in our result, we conducted meta-regression and sensitivity analysis to examine the sources of heterogeneity, where the definition of primary failure shows a remarkable relationship. PRAAVFs
Others, No. e e 1 angioendotheliomatosis 1 bleeding e 4 pseudoaneurysm 18 thrombophlebitis 7 partial wound dehiscence e
can be somewhat different depending on which vein branch is used, and this may be one source of the heterogeneity. However, we did not include veins in the meta-regression analysis because the original articles mainly simply described the chosen veins and lacked additional details such as vein diameters and the proportion of each vein. Owing to the same artery being used as the inflow, we consider there was homogeneity among 11 studies. Many other important factors not available in the original data, such as vessel diameters, initial intra-access blood flow, dialysis facility performance, and surgical expertise, might explain some difference in origins.34-37 According to the Dialysis Outcomes Practice Patterns Study data, the risk of initial AVF failure was 34% lower when performed by a surgeon with $25 fistula creations during training compared with those with
The outcome of the proximal radial artery arteriovenous fistula Cong Cong Wu, MD, Hua Jiang, MD, Jun Cheng, MD, Ling Fei Zhao, MD, Kai Xiang Sheng, MD, and Jiang Hua Chen, MD, Hangzhou, China Background: Guidelines recommend placing native arteriovenous fistulas (AVFs) as far distally in the upper extremity as possible. If there are adequate veins and adequate arteries, a wrist fistula, which offers notably lower risks than grafts and catheters, would be the first choice for long-term hemodialysis. With increasing failure and difficulty to create wrist fistulas, we reviewed outcomes of the proximal radial AVF (PRAAVF) and demonstrate that it is an effective technique. Methods: A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was primary failure, primary patency rates, and secondary patency rates after 1 and 2 years. Estimates were pooled with the random effects model, and meta-regression and sensitivity analysis were performed to explore heterogeneity. Results: According to selection criteria formulated a priori, 10 articles (n [ 1310) were included and finally analyzed after screening 1687 articles. The pooled primary failure was 12.3% (95% confidence interval [CI], 7.6%-17.0%; c2 [ 70.8, I2 [ 87.3%), the primary patency, including primary failure, was 73.6% (95% CI, 52.4%-94.9%; c2 [ 71.3, I2 [ 97.2%) at 1 year and 70.5% (95% CI, 50.6%-90.5%; c2 [ 58.8, I2 [ 96.6%) at 2 years. Secondary patency was 80.0% (95% CI, 72.8%-87.2%; c2 [ 24.42, I2 [ 75.4%) at 1 year and 73.7% (95% CI, 65.2%-82.2%; c2 [ 28.51, I2 [ 79.0%) at 2 years. Individual variate meta-regression analysis found the definition of primary failure was a significant source of heterogeneity (P [ .009). Steal syndromes developed in four of 832 (0.5%) of the PRAAVFs, and venous hypertension developed in four of 284 (1.4%). Conclusions: The PRAAVF presented low to moderate primary failure and high primary and secondary patency rates with acceptable complications. Consideration of the specific fistula is required when creating a vascular access, especially when a wrist fistula has failed or is predicted to be unsuccessful. (J Vasc Surg 2015;61:802-8.)
The native arteriovenous fistula (AVF) is recommended as the best vascular access for hemodialysis by the National Kidney Foundation Kidney Dialysis Outcomes Quality Initiative (NFK/DOQI) clinical practice guideline.1 Compared with grafts and catheters, AVFs have the longest patency duration and the least interventions.2,3 Patients with AVFs have the lowest risks of death, infections, and cardiovascular events4 and also the lowest costs to the health care system.3 The NFK/DOQI suggests an order of preference for vascular access of radial artery-cephalic vein From the Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University; the Key Laboratory of Nephropathy, Zhejiang Province; and the Kidney Disease Immunology Laboratory, The Third Grade Laboratory, State Administration of Traditional Chinese Medicine of PR China. This study was supported by funding from Key Projects in the National Science & Technology Pillar Program in the Twelfth Five-Year Plan Period (No. 2011BAI60B07). Author conflict of interest: none. Reprint requests: Jiang Hua Chen, MD, Zhejiang University, Kidney Disease Center, College of Medicine, 79 Qingchun Rd, Hangzhou 310003, China (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2015 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2014.08.112
802
AVF at the wrist, brachial artery-cephalic vein AVF in the upper arm, a transposed brachial artery-basilic vein AVF, or an arteriovenous graft. Catheters are discouraged as permanent vascular accesses.1 However, failure of AVFs created at the wrist and difficulty in maintaining patency seem to have increased in recent years because of the poor quality of distal veins and arteries, frequently owing to previous venous catheters, diabetes mellitus, peripheral vascular disease, and older age.3,5,6 Meanwhile, the brachial AVF has a higher risk of distal steal syndrome, arm ischemia, high-output heart failure,7 and right ventricular dysfunction8 than the wrist fistula. A suitable alternative to avoid the upper arm AVF is a fistula created in the proximal forearm, which was first described in 1977 by Toledo-Pereyra et al9 and Gracz et al10 as a proximal radial artery fistula. Toledo-Pereyra et al9 created the proximal radial artery fistula by connecting the proximal radial artery and the cephalic vein, whereas Gracz et al10 anastomosed the perforating branch of the median antecubital or cephalic vein end-to-side to the artery. Another choice is a middle-arm fistula reported by Bonforte et al11 in 2004, in which the proximal radial artery is anastomosed to the nearest vein (cephalic, median antebrachial, perforating vein). Previous studies9-11 have shown that fistulas using the proximal radial artery as the inflow have excellent patency rates, allowing for multiple access sites in the proximal forearm.10
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Considering the extensive public policy to promote fistula use, we performed a systemic review and pooled estimates of primary failure and 1-year and 2-year primary patency and secondary patency rates of the proximal radial artery AVF (PRAAVF). We aimed to improve the accuracy of the PRAAVF outcome estimates and explore an additional site and type of vascular access selection. METHODS Search strategy. A systemic literature search confined to all relevant published articles until January 1, 2014, about the PRAAVF was conducted in PubMed. The keywords used were proximal, radial, fistula, middle arm, cubital, forearm, and antebrachium. Bibliographies of selected articles were also searched by hand for any additional related reports. Selection criteria. Studies had to meet inclusion criteria, which were formulated a priori. Firstly, a study was eligible only if an AVFs was created with the PRA as the inflow in the forearm, irrespective of the type of anesthesia, the type of anastomosis, and the type of vein used to create the anastomosis. The median antebrachial vein, cephalic vein, perforating vein, and other veins were all eligible. Secondly, the study had to report one or more of the following outcomes: primary failure and the 1-year or 2-year primary patency and secondary patency rates. Investigations were included regardless of definitions of outcome, but most of the studies were in accordance with the Society for Vascular Surgery (SVS)/American Association of Vascular Surgery and the North American Vascular Access Consortium (NAVAC).12,13 Only articles written in English were included. We excluded studies if the PRA was used in a primary or staged transposition AVF procedure. Studies involving children or adolescents were excluded. Study definitions. Primary failure was defined as immediate vascular access failure as indicated by an access that had no appearance of or a loss of bruit or thrill #72 hours of creation (NAVAC12 definition). Early dialysis suitability failure was defined as an access that, despite radiologic or surgical intervention, could not be used successfully for dialysis by the third month after its creation (NAVAC12 definition). Late dialysis suitability failure was defined as an access that, despite radiologic or surgical intervention, could not be used successfully for dialysis by the sixth month after its creation (NAVAC12 definition). Primary patency was defined as the interval from the time of access placement until any intervention designed to maintain or re-establish patency, first occurrence to access thrombosis, or reaching a censored event (NAVAC12 and SVS13 definition). Secondary patency was defined as the interval from the time of access placement until access abandonment or achievement of a censored event, including intervening manipulations by surgical or endovascular interventions (NAVAC12 and SVS13 definition). Data extraction. We extracted information on year of publication, country, recruitment start date, sample size,
Fig 1. Flow diagram shows study eligibility and inclusion.
follow-up period, mean age, sex, proportion of diabetes mellitus, outcome definitions, primary failure, primary and secondary patency rates at 1 and 2 years, selection criteria of creating the PRAAVF, different veins anastomosed to the PRA, and complications. Most studies showed patency rates in the text, life-tables, or Kaplan-Meier curves. If the patency rate was only mentioned in a Kaplan-Meier plot, we estimated it from the curve. Statistical analysis. We calculated the estimates of primary failure and patency rates using the double arcsine transformation.14 The 95% confidence interval (CI) was calculated for each estimate with the Wilson score method.15 We performed the meta-analysis in Stata 12.0 software (StataCorp LP, College Station, Tex) with the commands metan (three variables: double-arcsine-transformed primary failure or patency rates, the lower Wilson CI, the upper Wilson CI), metareg, and metaninf. The presence of heterogeneity was assessed by the c2 test and I2 statistic. When heterogeneity was high (I2 > 75%), performing a random effects model was preferred. We further explored the sources of heterogeneity by meta-regression analysis, in which potentially relevant factors examined individually were year of publication, sample size, recruitment start date, mean age, proportion of men, proportion of diabetes mellitus, and definition of primary failure. Only factors that showed P < .05 were entered into a multiple regression model. Sensitivity analysis was conducted to investigate the specific study that might be the origin of heterogeneity. We also calculated additional pooled estimates of patency rates excluding primary failure. RESULTS Included studies We searched 1687 articles and reviewed 16. After ineligible studies were excluded, 11 (n ¼ 1422), published between 1977 and 2012, met our criteria. However, two eligible articles11,16 were published using the data from overlapping patients, so we only took into account the results from the article with larger sample. Therefore, 10 studies consisting of 1310 vascular accesses finally remained. Details of the study screening are presented in Fig 1. Study characteristics and patency rates extracted from each study are separately summarized in Table I.
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804 Wu et al
Table I. Study characteristics Study
Year
Country
No.
Recruitment start
Follow-up, months
Mean age, years
Male, %
DM, %
Toledo-Pereyra9 Bruns18 Roberts24 Jennings19 Weyde17 Kumar21 Bonforte16 Whittaker22 Bhalodia20 Capurro23
1977 2003 2005 2006 2007 2007 2010 2011 2011 2012
USA USA USA USA Poland India Italy UK UK Italy
20 73 58 134 77 320 459 58 19 92
e 1998 2003 2003 1992 1990 1991 2003 2006 2003
e e 10 11 e 54 22.8 e e 33
e 57 56 61 58 32 71.4 60 61 66
e 50.7 41.0 54.5 55.8 80.0 59.9 60.3 95.0 62.7
55.0 71.0 50.0 50.7 33.8 25.0 22.9 15.5 63.0 27.6
DM, Diabetes mellitus; UK, United Kingdom; USA, United States of America.
Fig 2. Primary failure of the proximal radial artery arteriovenous fistula (PRAAVF). Weights are from random effects analysis. Heterogeneity: c2 ¼ 70.8, I2 ¼ 87.3%. The solid squares denote the mean difference, the horizontal lines represent the 95% confidence intervals (CIs), and the diamond denotes the weighted mean difference. ES, Estimate.
Meta-analysis Primary failure. Estimates of the PRAAVF primary failure rate ranged from 1.2% to 32.9% (Fig 2), with a high degree of heterogeneity (c2 ¼ 70.8, df ¼ 9; I2 ¼ 87.3%). The random effects pooled primary failure rate of the PRAAVF was 12.3% (95% CI, 7.6%-17.0%). In individual variable meta-regression analysis exploring the sources of heterogeneity, the primary failure was higher in some studies where the definition appeared to include inferior fistulas (other fistulas except radiocephalic AVF and PRAAVF) as primary failed AVF (P ¼ .009; Table II). None of other factors showed any significant relationship with heterogeneity. In the sensitivity analysis, the pooled primary failure decreased to 10.4% (95% CI, 6.0%-14.8%) when we omitted the study17 in which the PRA was anastomosed only to the perforating vein because the superficial forearm veins were completely inadequate (Fig 3). One-year primary patency rate. Estimates of the 1year primary patency rate of the PRAAVF ranged from
Table II. Results of meta-regression analysis Primary failure
Coefficient
Year No. Mean age Male DM Recruitment start Definition of PFa
0.0044 0.0003 0.0002 0.0421 0.0292 0.0077 0.1597
95% CI 0.0042 0.0009 0.0087 0.6531 0.5293 0.0072 0.0527
to to to to to to to
0.0129 0.0002 0.0090 0.7372 0.4709 0.0226 0.2666
P .271 .229 .965 .890 .896 .260 .009
CI, Confidence interval; DM, diabetes mellitus; PF, primary failure. a Definition of primary failure appeared to include inferior fistulas as primary failed ones.
47.0% to 92.3%, with a high degree of heterogeneity (c2 ¼ 71.3, df ¼ 2; I2 ¼ 97.2%). The random effects pooled 1year primary patency rate of the PRAAVF was 73.6% (95% CI, 52.4%-94.9%) and was 85.7% (95% CI, 74.3%97.1%; c2 ¼ 34.51, I2 ¼ 94.2%) when primary failure was excluded from the calculation. Because of an insufficient
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Fig 3. Sensitivity analysis of primary failure. CI, Confidence interval.
number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. Two-year primary patency rate. The estimated 2year primary patency rate of the PRAAVF ranged from 43.1% to 86.7%, with a high degree of heterogeneity (c2 ¼ 58.8, df ¼ 2; I2 ¼ 96.6%). The random effects pooled 2year primary patency rate of the PRAAVF was 70.5% (95% CI, 50.6%-90.5%) and was 81.9% (95% CI, 70.193.8; c2 ¼ 32.42, I2 ¼ 93.8%) when primary failure was excluded. Because of an insufficient number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. One-year secondary patency rate. The estimated 1year secondary patency rate of the PRAAVF ranged from 62.6% to 91.4% (Fig 4), with a high degree of heterogeneity (c2 ¼ 24.42, df ¼ 6; I2 ¼ 75.4%). The random effects pooled 1-year secondary patency rate of the PRAAVF was 80.0% (95% CI 72.8%-87.2%) and was 95.5% (95% CI 92.6%-98.4%; c2 ¼ 10.45, I2 ¼ 42.6%) when primary failure was excluded. Because of an insufficient number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. Two-year secondary patency rate. The estimated 2year secondary patency rate of the PRAAVF ranged from 52.5% to 88.2% (Fig 5), with a high degree of heterogeneity (c2 ¼ 28.51, df ¼ 6; I2 ¼ 79.0%). The random effects pooled 2-year secondary patency rate of the PRAAVF was 73.7% (95% CI, 65.2%-82.2%) and was 87.4% (95% CI, 80.2-94.7; c2 ¼ 49.2, I2 ¼ 87.8%) when primary failure was excluded. Because of an insufficient number of eligible articles, meta-regression analysis and sensitivity analysis were not conducted. Every study mentioned that unfeasible veins or arteries, or both, in the wrist were one of selection criteria of creating the PRAAVF; however, only three18-20 articles
undertook actual measurements of the diameter and mentioned the minimal criteria as an artery diameter $2.0 mm and a vein diameter $2.5 mm. Four10,21-23 articles reported one of selection criteria to be a previously failed AVF in the wrist. Arteriosclerotic or calcified arteries and thrombosed or sclerosed veins in the wrist were deemed unsuitable to create a distal AVF in the wrist so that the PRAAVF could be a second choice.10,21-23 Roberts et al24 performed procedures to create PRAAVFs in the difficult access extremity where a wrist or upper arm brachiocephalic AVF was not possible or was predicted to fail. Weyde et al17 created the PRAAVFs in patients whose superficial forearm veins were completely occlusive or destroyed up to the cubital fossa by using the perforating vein as outflow. A more aggressive strategy was adopted by Bonforte et al,16 in which two or more factors among diabetes mellitus, atherosclerosis, obesity, neoplasm, coagulation disease, peritoneal dialysis failure, or age $65 years determined the PRAAVF as the first-choice vascular access. Different veins, such as the median antebrachial vein, cephalic vein, perforating vein, were chosen for the anastomosis to the PRA, depending on the preference or proficiency of the surgeons and the anatomic structure in the forearm. According to the study of Weyde et al,17 the perforating vein would be a good choice if use of the superficial forearm veins were not feasible. Meanwhile, the PRAAVF showed outstanding performance with few complications (Table III). Steal syndrome developed in four of 832 of the PRAAVFs (0.5%) based on eight studies. Three articles evaluated venous hypertension, which occurred in four of 284 of the PRAAVF (1.4%). DISCUSSION Generally, the vascular access has been considered to be not only the lifeline but also the Achilles’ heel of hemodialysis
806 Wu et al
JOURNAL OF VASCULAR SURGERY March 2015
Fig 4. One-year secondary patency of the proximal radial artery arteriovenous fistula (PRAAVF). Weights are from random effects analysis. Heterogeneity: c2 ¼ 24.42, I2 ¼ 75.4%. The solid squares denote the mean difference, the horizontal lines represent the 95% confidence intervals (CIs), and the diamond denotes the weighted mean difference. ES, Estimate.
Fig 5. Two-year secondary patency of the proximal radial artery arteriovenous fistula (PRAAVF). Weights are from random effects analysis. Heterogeneity: c2 ¼ 28.51, I2 ¼ 79.0%. The solid squares denote the mean difference, the horizontal lines represent the 95% confidence intervals (CIs), and the diamond denotes the weighted mean difference. ES, Estimate.
therapy. Despite all of the progress achieved since Brescia and Cimino25 introduced the native AVF in 1966, we still face a conundrum about vascular accesses. Fistulas patency is severely compromised by maturation failure, thrombosis, and stenosis. Intimal hyperplasia is thought to be the culprit lesion pathophysiologically in fistulas failing, with some potential contributors, such as outward remodeling and vascular pathology, mediated by chronic kidney disease.26 Considering the increasing number of patients with Brescia-Cimino fistulas that previously failed or in whom fistula creation at the wrist was predicted to be unfeasible, our research found the PRAAVF is a safe and reliable
alternative. In our study, the PRAAVF showed an attractive outcome: the primary failure was 12.3%, the primary patency rates were 73.6% and 70.5% after 1 and 2 years, and the secondary patency rates were 80.0% and 73.7% after 1 and 2 years. Kumar et al21 reported the mean time to fistula maturation was 26 6 5.2 days. Meanwhile, the meta-analysis by Al-Jaishi et al27 reported that the primary failure rate was 23%, the primary patency rates were 60% and 51% after 1 and 2 years, and the secondary patency rates were 71% and 64% of mixed upper arm and lower arm AVF patency. In their subgroup analysis, the primary patency rates of the radiocephalic
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Table III. Complications mentioned in studies
Study
Year
No.
Congestive heart failure, No.
Toledo-Pereyra9 Bruns18 Roberts24 Jennings19
1977 2003 2005 2006
20 73 58 134
0 e e e
0 0 0 2
e 1 e 3
e 0 e 0
e e 0 0
Weyde17 Kumar21
2007 2007
77 320
0 e
0 0
0 e
e 20
e e
Bonforte16 Whittaker22 Bhalodia20 Capurro23 Total
2010 2011 2011 2012
459 58 19 92
e e e e 0/97
e 1 e 1 4/832
e e e e 4/284
e e e e 20/527
e e e e 0/192
Steal syndromes, No.
Venous hypertension, No.
Infections, No.
Hospitalizations related to complications, No.
AVFs in lower arm were 55% overall and 46% at 1 year (n ¼ 1145) and 2 years (n ¼ 890), and the secondary patency rates were 68% overall and 58% at 1 year (n ¼ 937) and 2 years (n ¼ 682) years, including primary failure. Lok et al28 reported that the primary failure of radiocephalic AVFs (n ¼ 231) was 11.2%, including 9.1% for brachiocephalic (n ¼ 186) and 16% for brachiobasilic (n ¼ 25) AVFs. In the Maya et al29 study, the primary failure rates were 18% and 38% separately in brachiobasilic (n ¼ 67) and brachiocephalic (n ¼ 322) AVFs. Koksoy et al30 reported primary patency rates of 87% and 81% at 1 and 3 years for brachiocephalic AVFs (n ¼ 50) and 86% and 73% for brachiobasilic AVFs (n ¼ 50). The secondary patency rates at 1 and 3 years were 87% and 70% for brachiocephalic AVFs and 88% and 71% for brachiobasilic AVFs separately. Therefore, the PRAAVF could be a feasible choice with acceptable patency rates. In addition, the PRAAVF seemed to be associated with low risk of long-term or severe complications in our current investigation. We found steal syndromes developed in 0.5% (four of 832) of the PRAAVF compared with 10% to 25% of brachial artery AVFs and 1% to 1.8% of radiocephalic AVFs.31 van Hoek at al32 also reported that a cold hand developed in 50% of patients with brachiocephalic AVFs and in 12% with radiocephalic AVFs. Meanwhile, the upper arm fistula is related to an increased risk of high-output cardiac failure as a result of high vascular access flow.7 Left ventricular disorders and volume overload may induce or aggravate pulmonary hypertension, which is a rare disease but with high mortality.33 Paneni et al8 also reported right ventricular dysfunction can emerge in patients with brachial AVFs.8 Even though guidelines suggest a brachiocephalic fistula as the second choice, we deem the PRAAVF could be an additional, even better option, than the former. Because of significant heterogeneity in our result, we conducted meta-regression and sensitivity analysis to examine the sources of heterogeneity, where the definition of primary failure shows a remarkable relationship. PRAAVFs
Others, No. e e 1 angioendotheliomatosis 1 bleeding e 4 pseudoaneurysm 18 thrombophlebitis 7 partial wound dehiscence e
can be somewhat different depending on which vein branch is used, and this may be one source of the heterogeneity. However, we did not include veins in the meta-regression analysis because the original articles mainly simply described the chosen veins and lacked additional details such as vein diameters and the proportion of each vein. Owing to the same artery being used as the inflow, we consider there was homogeneity among 11 studies. Many other important factors not available in the original data, such as vessel diameters, initial intra-access blood flow, dialysis facility performance, and surgical expertise, might explain some difference in origins.34-37 According to the Dialysis Outcomes Practice Patterns Study data, the risk of initial AVF failure was 34% lower when performed by a surgeon with $25 fistula creations during training compared with those with
