Journal Pre-proof Predictors of primary functional maturation of autogenous radiocephalic arteriovenous fistula in a cohort of Asian patients Hai-Lei Li, Yiu Che Chan, Dongzhe Cui, Jingsi Liu, Mingchi Wang, Ning Li, Pearl Pai, Stephen W. Cheng PII:
S0890-5096(20)30006-6
DOI:
https://doi.org/10.1016/j.avsg.2019.12.029
Reference:
AVSG 4841
To appear in:
Annals of Vascular Surgery
Received Date: 11 August 2019 Revised Date:
27 September 2019
Accepted Date: 14 December 2019
Please cite this article as: Li HL, Chan YC, Cui D, Liu J, Wang M, Li N, Pai P, Cheng SW, Predictors of primary functional maturation of autogenous radiocephalic arteriovenous fistula in a cohort of Asian patients, Annals of Vascular Surgery (2020), doi: https://doi.org/10.1016/j.avsg.2019.12.029. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.
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Predictors of primary functional maturation of autogenous
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radiocephalic arteriovenous fistula in a cohort of Asian patients
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Hai-Lei LI1, Yiu Che CHAN1, 2, Dongzhe CUI1, Jingsi LIU1, Mingchi WANG1, Ning LI1, Pearl PAI3,4, Stephen W CHENG1, 2 1
Division of Vascular Surgery, Department of Surgery, The University of Hong Kong-Shenzhen hospital, Shenzhen, Guangdong Province, China.
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Division of Vascular Surgery & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China
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Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, Guangdong, China Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
AUTHOR CORRESPONDENCE: Dr. Yiu-Che CHAN MB BS BSc MD FRCS FRCS(General Surgery) FCSHK Associate Professor Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Pokfulam Road, Hong Kong. Tel: +852-2255-4962 FAX: +852-2255-4961 Email:
[email protected]
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Abstract
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Purpose: The aim of this study was to investigate the predictors of autogenous
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radiocephalic arteriovenous fistula (RCAVF) maturation.
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Methods: This was a retrospective analysis of patients undergoing RCAVF creation
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from June 2013 to December 2018 at a single medical center. Comparison of the
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variables between the matured and non-matured group was performed.
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Results: A total of 277 patients (male 173, 62.5%) with a mean age of 56.6 ± 16.9
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years old underwent primary RCAVF creation during the study period. The mean
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diameter of cephalic vein and radial artery were 2.4 ± 0.6mm (range 1.5 to 4.3 mm)
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and 2.3 ± 0.5 mm (range 1.5 to 4.0 mm), respectively. Primary functional maturation
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was achieved in 236 patients (236/277, 85%). There was no statistical significance
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between the matured and non-matured group in terms of age (56.4±14.8 vs
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58.1±15.1, p=0.498), coronary arterial disease (12% vs 17%, p=0.449), diabetes
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mellitus (42% vs 39%, p=0.864), smoking (26% vs 22%, p=0.699) or antiplatelet
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therapy (23% vs 24%, p=0.844). However, female gender (35% vs 54%, p=0.024),
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peripheral arterial disease (9% vs 22%, p=0.025), small vein (2.4±0.5mm vs
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2.0±0.5mm, p<0.01) and artery (2.4±0.5 vs 2.1±0.4, p<0.01) diameter were
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associated with the failure of maturation. The best cutoff diameter for cephalic vein
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and radial artery was 1.85mm and 2.05mm, respectively.
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Conclusions: In this cohort of patients undergoing RCAVF creation, vein and artery
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diameter on preoperative ultrasound mapping was the predictor of functional
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maturation. Female gender and presence of peripheral arterial disease were
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associated with failure of maturation.
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Keywords: arteriovenous fistula; hemodialysis; vascular access; vessel diameter;
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maturation.
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Introduction
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Hemodialysis is a definitive treatment for most of the patients who have end-stage
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renal disease. A patent vascular access with sufficient blood flow is crucial to
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deliver adequate hemodialysis. Autogenous arteriovenous fistula (AVF) is the
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optimal vascular access for hemodialysis because it has the higher patency rate with
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fewer complications compared with prosthetic conduit or central venous catheter1, 2,
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3.
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recommended as the first choice for primary AVF if the vascular anatomy is suitable,
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as the possibility of proximal AVF in the ipsilateral arm can be preserved in case the
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primary AVF fails4. Arterial and venous mapping with duplex ultrasound before
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fistula creation has been shown to increase the success of AVF construction and
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patency5, 6, 7, 8. Despite of routine preoperative mapping and various efforts, the
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incidence of maturation failure remains high. A primary failure rate of 15.3% has
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been indicated in a meta-analysis9.
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Various factors potentially affecting fistula maturation have been studied, however,
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the sample size was small and the conclusion derived from these papers was not
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consistent. There has been a lot of debate on the optimal range of radial artery and
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cephalic vein for best maturation outcome of RCAVF, it is recommended to be at
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least 2.oomm in a systematic review10. However, there is no evidence in Asian
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population, it is reported the cause of renal failure is different in Eastern countries11
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and Asian patient has a smaller vessel12. The purpose of this study was to
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investigate variables affecting autogenous RCAVF maturation in a cohort of Asian
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patients. These factors included patient demographics (age, gender) and
Radiocephalic arteriovenous fistula (RCAVF), also Brescia-Cimino AVF is
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comorbidities (hypertension, diabetes mellitus, coronary and peripheral arterial
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disease, and smoking), anatomical variance (diameter of the vein and artery), and
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perioperative antiplatelet therapy. Especially, we focused on the correlation
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between preoperative vessel diameter and AVF maturation outcome. Furthermore,
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we performed a stepwise analysis of the best cutoff diameter of cephalic vein and
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radial artery for optimal functional maturation.
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Methods
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A prospective consecutive study of patients undergoing hemodialysis access
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creation from June 2013 to December 2018 at a single medical center was
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conducted. Only the patients received placement of a primary RCAVF were included.
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Brachiocephalic or brachiobasilic was excluded because an additional procedure to
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superficialize or translocate the vein was often required, those surgical procedures
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may affect maturation. Patients with a previous failed arteriovenous fistula or graft
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undergoing a new vascular access were excluded in this study cohort.
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Vascular size and quality were standardly assessed before operation. Arterial
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assessments included blood pressure in both upper extremities, pulse examination
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and Allen’s test for competence of the palmar arch. Gross examination of venous
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system was carried out in a warm room with venous tourniquet occlusion at the
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upper arm. As an adjunct to physical examination, preoperative vessel mapping with
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duplex ultrasound was routinely performed at our vascular ultrasound lab by the
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same two experienced vascular ultrasound technologists and interpreted by a
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vascular surgeon during the study period. Vessel mapping was performed without a
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tourniquet using a Hitachi (HI VISION Preirus) ultrasound machine with a high-
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frequency (5-9 MHz) linear transducer. Patient lied supine with the arm to be
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examined rotated externally. Great care was taken during the examination to
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prevent too much compression on the vessels which may cause inaccurate results.
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Vein diameter was measured at the following representative sites, wrist, distal
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forearm, mid-forearm, proximal forearm, antecubital fossa, distal upper arm, mid-
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upper arm and proximal upper arm, the data was recorded on a standardized form.
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We used the minimum vein diameter in the analysis because the smallest part of
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outflow vein is an important predictor of potential pre-existing stenosis and failure
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to maturation. Radial, ulnar and brachial arteries were evaluated for presence or
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absence of calcification. Diameter of radial artery was measured at wrist.
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Autogenous RCAVF was placed under local or regional anesthesia by one of the
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three surgeons who performed all the hemodialysis access operations. End to side
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arteriovenous anastomosis was performed using a 6-0 PROLENE® (Ethicon Inc,
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Somerville, NJ) running suture with administration of systemic heparin. Patients
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were seen in 4 to 6 weeks postoperatively to assess adequate maturation.
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Maturation status was evaluated with physical examination combined with duplex
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ultrasound scan on the first clinic follow-up. If the fistula is satisfactory both on
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physical examination and duplex ultrasound, we consider it is ready to use.
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Baseline patient demographic characters including age, gender, and comorbidities
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were documented in a prospectively collected research database. Data was reported
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according to the reporting standards for arteriovenous accesses of the Society for
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Vascular Surgery13. Primary fistula functional maturation was defined as successful
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cannulation of fistula with adequate flow volume for three consecutive dialysis
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sessions13.
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Statistical analysis
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Statistical analyses were performed using SPSS Statistics, version 22.0 (IBM Corp,
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Armonk, NY). The patients were allocated to two groups according to functional
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maturation outcome. Results were expressed as mean ± standard deviation for
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normal distribution data. The χ2 test was used to compare ratios and Student t-test
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was used to compare continuous variables between the matured and non-matured
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group. A two-sided P-value < 0.05 was considered statistically significant. The
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optimal cutoff diameter of radial artery and cephalic vein was calculated using
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receiver operating characteristic (ROC) curve, which is a mapping of sensitivity
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versus 1-specificity for all possible values of the cut-point. A simultaneous
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assessment of sensitivity and specificity was required to identify the best cut-point,
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which was considered to maximize the combination of sensitivity and specificity.
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Results
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Patient demographics
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Between June 2013 and December 2018, 306 autogenous hemodialysis accesses
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were created as the first time permanent hemodialysis accesses at our single
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medical center, including 286 radiocephalic, 12 brachiocephalic and 8 brachiobasilic
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AVFs. Twenty-eight patients underwent re-do access procedure after a failed prior
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AVF. Only one arteriovenous graft fistula was performed during the study period.
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Nine patients with RCAVF were excluded for being lost to follow-up. A total of 277
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patients were included in this study. The clinical characteristic of the 277 patients
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subjected to primary RCAVF creation with adequate follow-up was summarized in
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Table 1. The mean age was 56.6 ± 16.9 years old (range 21 to 86). Majority
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(173/277, 62.5%) of the patients were male. Almost all patients (260, 94%)
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presented with hypertension, 114 patients (41%) had diabetes mellitus, 36 (13%)
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had documented coronary arterial disease, 30 (11%) had peripheral arterial
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disease, and 70 patients (25%) were smokers. Sixty-five patients (23.5%) were on
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aspirin or clopidogrel before the procedure. Pre-operative duplex mapping of vein
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and artery was performed in all the patients. The mean diameter of cephalic vein
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and radial artery were 2.4 ± 0.6mm (range 1.5 to 4.3 mm) and 2.3 ± 0.5 mm (range
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1.5 to 4.0 mm), respectively.
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Predictors of functional maturation
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The primary functional maturation was achieved in 236 (85%) individuals. There
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was no statistical significance between the matured and non-matured group in
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terms of age (56.4±14.8 vs 58.1±15.1, p=0.498), coronary arterial disease (12% vs
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17%, p=0.449), diabetes mellitus (42% vs 39%, p=0.864), smoking (26% vs 22%,
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p=0.699) or antiplatelet therapy (23% vs 24%, p=0.844). However, female patients
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(35% vs 54%, p=0.024), peripheral arterial disease (9% vs 22%, p=0.025), small
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vein (2.4±0.5mm vs 2.0±0.5mm, p<0.01) and artery (2.4±0.5 vs 2.1±0.4, p<0.01)
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diameter were associated with the failure of maturation (Table 2).
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Furthermore, ROC curve was used to estimate the optimal cut-point for the
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diameter of cephalic vein and radial artery. The best cutoff diameter for cephalic
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vein and radial artery was 1.85mm (Table 3, Figure 1) and 2.05mm (Table 4, Figure
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2), respectively. Patients with a cephalic vein ≥ 1.85mm in diameter had a significant
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functional maturation rate (93% vs 53%, p<0.01). When radial artery was larger than
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2.05mm there was also a statistical increase in functional maturation (92% vs 74%,
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p<0.01).
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Discussion
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In this cohort of Asian patients undergoing RCAVF placement, the primary
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functional maturation was achieved in 85% of subjects. We observed that female
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gender, diameter of cephalic vein and artery, and presence of peripheral arterial
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disease were associated with fistula maturation. Our study suggested patients with
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a cephalic vein ≥ 1.85mm (93% vs 53%, p<0.01) and radial artery ≥ 2.05mm (92% vs
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74%, p<0.01) had a significant functional maturation outcome.
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Majority of hemodialysis accessed done at our institution were RCAVF, because
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patients with end-stage renal disease (ESRD) were referred early for evaluation and
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vein mapping. We use end-to-side anastomosis for AVF creation in our practice, it
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has been demonstrated superior than side-to-side configuration14. Female gender
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was associated with failure of maturation in this study, it is consistent with other
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published studies15, 16. We identified that patients with peripheral arterial disease
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had a significant risk of failure to mature. Chen et al17 reported that ankle-brachial
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Index <0.9 was significantly correlated with hemodialysis access failure.
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Although previous reports suggested diabetes mellitus leading to failure of
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maturation, we did not observe a significant difference on maturation between the
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diabetic and non-diabetic patients. Theoretically, diabetes will affect artery and
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cause calcification. The role of atherosclerosis had already been taken into account
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by preoperative ultrasound assessment which would be reflected in the radial
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artery diameter. In addition, previous studies did not include both arterial and
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venous caliber into analysis when describing diabetes as a predictor of maturation
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failure. There is evidence that careful patient selection, surgical skill and experience
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could tackle the most of the problems in vascular access procedures for diabetic
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patients18. In this study, 85% of the fistulas were successfully used for hemodialysis.
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It is logical that increased vessel diameter is associated with better flow and fistula
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maturation, and this has been demonstrated in several previous published articles19,
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20, 21.
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placement, the exact cutoff of the preoperative vessel size is controversial. Wong et
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al22 found radial artery and cephalic vein diameter less than 1.6 mm was associated
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with early fistula failure. While, Reilly et al12 reported vein less than 2 mm and
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arteries less than 2.9 mm were more likely associated with early dysfunction. We
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found the optimal cutoff diameter of cephalic vein and radial artery were 1.85mm
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and 2.05mm, respectively. Kordzadeh et al23 reported that cephalic vein diameter
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>1.5mm and radial artery diameter >1.6mm were independent predictors of RCAVF
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maturation, a primary functional maturation of 86% can be anticipated if both
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criteria are met.
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Patients were selected for RCAVF based on vessel diameter from preoperative
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duplex. All comers for AVF creation at our institution would have preoperative
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duplex mapping. In this study, the minimal vein and artery diameter was 1.5mm.
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Wrist RCAVF was our first choice to preserve proximal vein, a more proximal AVF
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configuration at forearm will be considered if wrist RCAVF is not anatomically
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feasible. We did not deliberately only choose favorable patients, but if the maximum
Although preoperative ultrasound mapping improved the success rate of AVF
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vein diameter was less than 1.5mm, we would look for other sites for access. In the
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current study, there were no cases of bleeding or haematoma formation which
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require re-exploration. All the patients were discharged from hospital on
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postoperative Day 1 after an overnight observation, and wounds were all inspected
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upon discharge and at the outpatient clinic.
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We noticed that the blood flow rate that required for adequate hemodialysis is
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lower in Asian patients. For example, hemodialysis is typically performed at a flow
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rate of 250-300ml/min in China, while in the United States, dialysis flow is 350-
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450ml/min24. All of the patients in this study were of Chinese ethnicity. A few
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studies have reported ethnic differences in arm vein diameter and AVF creation 25,
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26.
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cephalic vein and radial artery was 2.9±0.8mm and 2.6±0.6mm in the 663 patients
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undergoing RCAVF creation27. In our study, the diameter of cephalic vein and radial
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artery was 2.4±0.6mm and 2.3±0.5mm, respectively. These may reflect that Asian
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patients have a smaller vessel compared with Europeans. The etiology of ESRD was
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also different between Western and Eastern. It has been reported that chronic
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glomerulonephritis was the cause of ESRD in 50% of the cases in China, whereas it
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causes around 20% of ESRD in UK11. In this cohort of patients, 41% were diabetic.
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We did not have the exact data regarding the cause of renal failure as many of the
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patients presented for the first time with advanced kidney disease. The most
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common causes of renal failure in this cohort of patients were chronic
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glomerulonephritis and diabetes mellitus.
In a large cohort of hemodialysis patients in the Netherlands, the diameter of
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To our best knowledge, this is the largest study to report the correlation between
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preoperative vessel size and the RCAVF maturation outcome in Asian patients.
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However, the limitations of our study should be pointed out. First, the decision of a
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particular location to place the AVF was made according to the surgeon assessment,
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patients with very small vein may undergo graft placement or AVF creation at an
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alternative site. Therefore, there is bias in selecting patients in this retrospective
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study. In addition, nine patients were lost to follow-up. Further more, the data of the
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flow rate to determine dialysis adequacy was not available. We did not collect data
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on vessel calcification. We found the mean diameter of cephalic vein in the non-
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matured group was 2.0mm, however, based on ROC analysis the threshold of 1.85
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mm was a cutoff for failure of maturation. Although the sample size was robust, it
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was still difficult to ascertain which measurement would recommend be used in
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practice.
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Conclusions
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In this cohort of patients undergoing radiocephalic AVF creation, vein and artery
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diameter on preoperative ultrasound mapping was the predictor of functional
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maturation. The best cutoff diameter for cephalic vein and radial artery was
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1.85mm and 2.05mm, respectively. Female gender and presence of peripheral
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arterial disease were associated with failure of maturation.
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Conflict of interest
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The authors declared no conflict of interest, no funding received in this study.
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Ethical statement
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This study was carried out in accordance with the Declaration of Helsinki and
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approved by the Institutional Ethical committee.
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Illustrations
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Table 1. Clinical and demographic characteristics for primary radiocephalic
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arteriovenous fistula
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Table 2. Comparison of variables affecting fistula functional maturation
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Table 3. Coordinates of cephalic vein diameter for area under curve
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Table 4. Coordinates of radial artery diameter for area under curve
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Figure 1. Area under the ROC curve for calculation of the best cutoff of cephalic vein
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diameter
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Figure 2. Area under the ROC curve for calculation of the best cutoff of radial artery
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diameter
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Reference
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fistula versus expanded polytetrafluoroethylene graft fistula for angioaccess in
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hemodialysis. Am J Surg 1986;152:238-243.
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2. Perera GB, Mueller MP, Kubaska SM, et al. Superiority of autogenous arteriovenous
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hemodialysis access: Maintenance of function with fewer secondary interventions. Ann
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3. Huber TS, Carter JW, Carter RL, Seeger JM. Patency of autogenous and
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4. Rayner HC, Besarab A, Brown WW, et al. Vascular access results from the Dialysis
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Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines. Am J Kidney Dis
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2004; 44(5 Suppl. 2):22-26
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7. IIhan G, Esi E, Bozok S, et al. The clinical utility of vascular mapping with Doppler
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Access 2013;14:83-8.
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8. Georgiadis GS, Charalampidis DG, Argyriou C, et al. The necessity for routine pre-
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9. Rooijens PPGM, Tordoir JHM, Stijnen T, Burgmans JPJ, Smetde AEA, Yo TI.
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primary failure rate. Eur J Vasc Endovasc Surg 2004;28:583-9.
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diameter is the major predictor of fistula maturation. J Vasc Surg 2009;49:1499-504.
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21. Dageforde LA, Harms KA, Feurer ID, Shaffer D. Increased minimum vein diameter
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on preoperative mapping with duplex ultrasound is associated with arteriovenous fistula
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Endovasc Surg 2017;53:726-32.
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MH, et al. Hemodialysis arteriovenous fistula maturity: US evaluation. Radiology
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in arm vein diameter and arteriovenous fistula creation rates in men undergoing
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27. Voorzaat BM, van der Bogt KEA, Janmaat CJ, van Schaik J, Dekker FW, Rotmans JI,
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2018;42:1895-1903.
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Table 4. Coordinates of radial artery diameter for area under curve Radial artery diameter (mm) 1.550 1.650 1.750 1.850 1.950 2.050 2.150 2.250 2.350 2.450 2.550 2.650 2.750 2.850 2.950 3.050 3.150 3.250 3.350 3.450 3.550
Sensitivity
Specificity
Sensitivity + specificity
.987 .958 .949 .915 .873 .686 .644 .547 .475 .436 .347 .305 .280 .220 .165 .106 .076 .072 .051 .025 .021
0.073 0.098 0.171 0.341 0.39 0.634 0.634 0.732 0.805 0.805 0.854 0.902 0.902 0.927 0.927 0.951 0.951 0.976 0.976 0.976 0.976
1.06 1.056 1.12 1.256 1.263 1.32 1.278 1.279 1.28 1.241 1.201 1.207 1.182 1.147 1.092 1.057 1.027 1.048 1.027 1.001 0.997
Table 3. Coordinates of cephalic vein diameter for area under curve Cephalic vein diameter (mm) 1.55 1.65 1.75 1.85 1.95 2.05 2.15 2.25 2.35 2.45 2.55 2.65 2.75 2.85 2.95 3.05 3.15 3.25 3.35 3.45
Sensitivity
Specificity
Sensitivity + specificity
0.979 0.962 0.949 0.881 0.843 0.685 0.634 0.579 0.528 0.472 0.374 0.294 0.226 0.204 0.157 0.106 0.081 0.081 0.072 0.047
0.244 0.341 0.366 0.634 0.659 0.707 0.707 0.732 0.756 0.78 0.902 0.902 0.902 0.902 0.902 0.927 0.927 0.976 0.976 0.976
1.223 1.303 1.315 1.515 1.502 1.392 1.341 1.311 1.284 1.252 1.276 1.196 1.128 1.106 1.059 1.033 1.008 1.057 1.048 1.023
Table 1. Clinical and demographic characteristics for primary radiocephalic arteriovenous fistula Characteristics
Number (%)
Total patients in analysis Age (y) Mean Range Gender Male Female Comorbidities Hypertension Diabetes mellitus Coronary arterial disease Peripheral arterial disease Tobacco use Preoperative vein diameter (mm) Mean Range Preoperative artery diameter (mm) Mean Range Functional maturation
277(100) 56.6 ± 16.9 21-86 173 (62.5) 104 (37.5) 260 (94) 114 (41) 36 (13) 30 (11) 70 (25) 2.4 ± 0.6 1.5-4.3 2.3 ± 0.5 1.5-4.0 236 (85.2)
Table 2. Comparison of variables affecting fistula functional maturation Variables
Matured (N=236)
Non-matured (N=41)
P value
Age
56.4±14.8
58.1±15.1
0.498
Female gender
82
22
0.024
Diabetes mellitus
98
16
0.864
Coronary arterial disease
29
7
0.449
Peripheral arterial disease
21
9
0.025
Tobacco use
61
9
0.699
Vein diameter (mm)
2.4±0.5
2.0±0.5
<0.001
Artery diameter (mm)
2.4±0.5
2.1±0.4
<0.001
Antiplatelet therapy
55
10
0.844