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STUDY OF THE CAUSES OF IMMATURITY
OF THE ARTERIO-VENOUS FISTULA FOR
HEMODIALYSIS
By
Mohamed Mahmoud Abdel-Rahman Morsi Hawary
(M. B. B.Ch.)
A thesis submitted in partial fulfillment
Of
The requirements for the degree of
Master
In
General Surgery
DEPARTMENT OF SURGERY
FACULTY OF MEDECINE
FAYOUM UNIVERSITY
2015
STUDY OF THE CAUSES OF IMMATURITY
OF THE ARTERIO-VENOUS FISTULA FOR
HEMODIALYSIS
By
Mohamed Mahmoud Abdel-Rahman Morsi Hawary
(M. B. B.Ch.)
Supervisors
Prof. Ayman Essawy
Professor of General and Vascular Surgery
Faculty of Medicine, Fayoum University
Dr. Mohamed AL-Maadawy
Ass. Professor of General and Vascular Surgery
Faculty of Medicine, Cairo University
Dr. Salah Said Soliman
Lecturer of General Surgery
Faculty of Medicine, Fayoum University
Fayoum University
2015
ACKNOWLEDGE
First of all I would like to thank ALLAH, who gave me everything.
I’m obliged to my PARENTS for everything for support and patience.
I would like also to express my sincere appreciation to Prof. Dr. Ayman
Essawy, Professor of General and Vascular surgery, Faculty of Medicine,
Fayoum University, for his fatherly support and encouragement.
My special thanks are dedicated to Dr. Mohamed Al-Maadawy, Professor
of General and Vascular surgery, Faculty of Medicine, Cairo University,
for his unlimited co-operation and guidance.
I can’t thank enough Dr. Salah Said Soliman, Lecturer of General
surgery, Faculty of Medicine, Cairo University, who shared me the
burden of completing this work, for his meticulous supervision all
through this thesis.
I’m obliged to all my professors, my seniors, my colleagues and my
friends.
CONTENTS
Page
ACKNOWLEDGE I
CONTENTS II
LIST OFACRONYMS AND ABBREVIATIONS III
LIST OF TABLES VI
LIST OF FIGURES VII
ABSTRACT VIII
INTRODUCTION 1
REVIEW OF LITERATURE
Vascular access for hemodialysis 2
Physiology of fistula maturation 19
Overall care of hemodialysis patient 33
Monitoring and Surveillance 40
Access dysfunction and complications 50
Management of dysfunctional access 78
PATIENTS AND METHODS 98
RESULTS AND DEMOGRAPHICS 103
DISCUSSION 116
SUMMARY 122
REFERENCES 124
ARABIC SUMMARY
LIST OF ACRONYMS AND ABBREVIATIONS
AA Autogenous access
AAVS American association of vascular surgery
ACE Angiotensin converting enzyme inhibitor
ACR-SIR American college of radiology-Society of interventional
radiology
atm. Atmosphere
APP Assisted primary patency
AV Arterio-venous
AVF Arterio-venous fistula
AVG Arterio-venous graft
BAM Balloon angioplasty maturation
BT Brachytherapy
CDDU Color Doppler duplex ultrasound
CCDU Color coded Doppler Ultrasound
CE-MRA Contrast-enhanced magnetic resonance angiography
CKD Chronic kidney disease
CPG Clinical practice guidelines
QOL Quality of life
CMS Centre for Medicare and Medicaid services
CPM Clinical performance measure
CP Cumulative patency
CRB Catheter related bacteremia
CVC Central venous catheter
DDAVP 1-deamino-8-D arginine vasopressin
DM Diabetes Mellitus
DOPPS Dialysis outcome and practice pattern study
DRIL Distal revascularization interval ligation
DSA Digital subtraction angiography
DVP Dynamic venous pressure
EDV End diastolic velocity
ESRD End stage renal disease
EC Endothelial cell
EVM Endovascular management
Ebselen PZ 51 or DR3305, a mimic of glutathione peroxidase
EPC Endothelial progenitor cell
FFBI Fistula First Breakthrough Initiative
GCSF Granulocyte colony stimulating factor
GFR Glomerular filtration rate
GSV Great saphenous vein
HD Hemodialysis
HO Haemo-oxygenase
THN Hypertension
IV Intra-venous
Kt/V K:dialyzer clearance(ml/min), t: time(min), V:volume of
patient body water
KRT Kidney replacement therapy
M Monitoring
MDT Multidiscipline team
MSCTA Multi-slice computed tomographic angiography
MMT Matrix Metalloproteases
MP Metalloproteases
MT1-MMT Membrane type 1 matrix metalloproteinase
MTHFR Methylene tetrahydrofolate reductase
MCP-1 Macrophage chemotactic protein-1
PAI-1 Plasminogen activator inhibitor type -1
NKF-
K/DOQI
National Kidney Foundation’s Kidney Dialysis Outcome
Quality Initiative
NIH Neointimal hyperplasia
NO Nitrous oxide
NVAII National Vascular Access Improvement Initiative
NAPRTCS North American pediatric renal trials and collaborative
studies
PA Prosthetic access
PDGF Platelet derived growth factor
PICC Peripherally inserted central catheter
Phox Phagocyte oxidase
PMT Percutaneous mechanical thrombectomy
PSV Peak systolic velocity
PRT Proteon therapeutic
PTA Percutaneous trans-luminal angioplasty
PTFE poly-tetra-flouro-ethylene
PP Primary patency
QIP Quality improvement project
QA Flow rate in Access
RI Resistance index
RRT Renal replacement therapy
S Surveillance
SCVIR Society of cardiovascular interventional radiology
SVS Society for vascular surgery
TC Tunneled catheter
TGF Transforming growth factor
TLR Toll like receptor
TNF Tumor necrosis factor
USRDS United States Renal Data System
VA Vascular access
VEGF-D Vascular endothelial growth factor D
VSMC Vascular smooth muscle cell
WSS Wall shear stress
LIST OF TABLES
No. Title of table Page
No.
1 Stages of Chronic Kidney Disease 1
2 Arterial requirements for AVF 8
3 Venous requirements for AVF 9
4 Prognostic factors affecting patency of vascular access 65
5 Causes of early fistula failure 69
6 Frequencies of demographic characters among studied patients 103
7 Frequencies of Types of arterio-venous fistulae among studied patients 105
8 Frequencies of Modes of Interventions among studied patients 106
9 Frequencies of Endovascular access among studied patients 107
10 Frequencies of different causes of failed AVF Maturation among studied
patients. 108
11 Frequencies of Failure of surgical intervention among studied patients. 109
12 Comparison of age among different causes of failure 110
13 Comparison of different causes of failure among different gender 111
14 Comparison of different causes of failure among diabetic groups 111
15 Comparison of different causes of failure among hypertension groups. 112
16 Comparison of different causes of failure among types of AVF 113
17 Comparison of different causes of failure among results of intervention. 113
18 Comparison of different causes of failure among results of intervention. 114
LIST OF FIGURES
No. Title of figure
Page
No.
1 Overview of fistula maturation 20
2 Vascular remodeling 55
3 Endothelial progenitor cells 58
4 Juxta-anastomotic stenosis 70
5 Accessory vein 72
6 Age groups and number of studied patients 104
7 frequency of Sex in studied group 104
8 Risk factors among study groups 104
9 Types of AVFs among study group 105
10 Types of interventions among study group 106
11 Types of Endo-vascular access among study group 107
12 causes of failed AVFs Maturation 108
13 Frequencies of Failure of surgical intervention among studied
patients.
109
14 Mean age among different failure causes
110
15 Different causes of failure among diabetic groups 112
ABSTRACT
Background: ESRD is a major public health problem. Vascular access to
facilitate hemodialysis is provided by one of the following three options:
native AVFs, prosthetic AVGs and CVC. Native AVFs are the preferred
mode of vascular access worldwide due to its ability to provide high
blood flow rates with superior patency and low rate of complications.
Several techniques have been described to maintain a hemodialysis
access site; varying from open surgery to endovascular approaches and
sometimes a hybrid one.
Aim of the work: To study cause of failed AVFs maturation and the
roles played by age, sex, DM, hypertension and evaluate the role of
endovascular interventions in assisted maturation.
Patients and Methods: Between April 2014 and January 2015, thirty
patients fulfilling our eligibility criteria with immature fistulae were
followed up during the period of maturation (6-8 weeks) and for the first
3 sessions.
Results: Our study included 30 cases with age range from 22-65 years
with 66.6% in the age 40-59 group. Female patients represented 60%.
36.6% of patients have DM and 40% have hypertension and 20% have
both. Central venous stenosis was the most common cause of failure to
mature with a percentage of 30% (9/30). Juxta-anastomotic venous
stenosis came next with percentage of 23.3%. Brachio-cephalic shunt
made 40% of AVFs failed to mature. The most common presentations
were weak thrill and pulse with no thrill (23%) each followed by swelling
of the upper limb (20%). Open surgery was done for 30% and EVM was
done for the rest.
Conclusion: The native (AVF) is recommended as the first choice due to
its superior patency and lower complication rates over grafts and
catheters.. EMDA can save many AVFs. Female patients percentage was
60% but no statistical difference with males patients (P=0.1). Also
diabetic patient has more chance to fail to mature. Central venous stenosis
is the leading cause of failure to mature AVFs especially in old age. Old
patient has more arterial causes than others. Brachio-cephalic and radio-
cephalic AVFs had the highest % of failure to mature. DUS is invaluable
tool in ESRD patient eligible for VA placement regarding monitoring and
early salvage prior to thrombosis.
Key Words: vascular access, hemodialysis, access immaturity, access
dysfunction, PTA.
INTRODUCTION
Chronic hemodialysis became a feasible treatment for end-stage
renal disease since 1960 after Quinton and Scribner devised an external
shunt that provided repetitive access to the circulation. The subsequent
development of vascular access techniques and devices now permits
patients to be maintained on dialysis for decades. The ideal vascular
access system should provide reliable and repetitive access to the
circulation, flow rates sufficient to deliver efficient dialysis, prolonged
patency, and low complications rates (Ayumi S. et al 2013)
However, the significant morbidity and cost associated with the
establishment and maintenance of vascular access in the hemodialysis
patients is an indicator of how far we are from achieving the ideal
vascular access system (Bernado F. et al 2011)
Hemodialysis access failure is the most common cause of
hospitalization for patients on regular hemodialysis. Vascular access
establishment and maintenance account for about 17% of total Medicare
spending for hemodialysis patients in the United. The social impact of
vascular access failure has been magnified by the dramatic growth in the
number of patients with end-stage renal disease over the past decade.
Between 1991 and 2001, the number of patients in the Medicare End-
stage Renal Disease program doubled from 207,000 to more than
400,000, and this number is expected to expand well into the twenty-first
century (Clemente N. et al 2014)
A technological breakthrough that would significantly reduce the
morbidity and cost associated with vascular access does not appear to be
in the horizon, and with this realization in mind, recent efforts have
focused on developing algorithms to better define patient selection
criteria for each access method (Reinhold C. 2011)
REVIEW OF
LITERATURE
VASCULAR ACCESS
FOR HEMODIALYSIS
Vascular access for hemodialysis
End stage renal disease (ESRD), and the maintenance of
hemodialysis access, is a tremendous public health problem that has
reached near epidemic proportions. Vascular access continues to be a
leading cause for hospitalization and morbidity in patients with chronic
kidney disease (CKD) stage 5. (Centers for Medicare & Medicaid Services:
2013 Annual Report).
The Kidney Disease Outcomes Quality Initiative (K/DOQI) has
developed a classification of chronic kidney disease (CKD) which is now
widely used, despite some reservations.
Stage Description GFR(ml/min/1.73m2)
1 Kidney damage with normal or ↓
GFR
< 90
2 Mild ↓ GFR 60-90
3 Moderate ↓ GFR 30-59
4 Severe ↓ GFR 15-29
5 Kidney Failure >15 or dialysis
Table 1- Stages of Chronic Kidney Disease (CKD)
Appropriate care of hemodialysis (HD) patients with CKD stage 5
requires constant attention to the maintenance of vascular access patency
and function. Vascular access still remains the ―Achilles’ heel‖ of the
procedure (Allon M et al, 2002). An ideal access delivers a flow rate to the
dialyzer adequate for the dialysis prescription, has a long use-life, and has
a low rate of complications (e.g. infection, stenosis, thrombosis,
aneurysm, and limb ischemia). Of available accesses, the surgically
created fistula comes closest to fulfilling these criteria. It seems that the
native arteriovenous fistula that Brescia and Cimino described in 1966
still remains the first choice VA. Studies over several decades
consistently demonstrate that native fistula accesses have the best 4- to 5-
years patency rates and require the least interventions compared with
other access type (Santoro A et al, 2006)
Total Medicaid outlays in Federal fiscal year (FY) 2012 were
$431.9 billion; $250.5 billion or 58 percent represented Federal spending,
and $181.4 billion or 42 percent represented State spending. (CMS,CPM
2013).
Before the first dissemination of the Dialysis Outcomes Quality
Initiative (DOQI) recommendations on vascular access in 1997, many
studies showed that practice patterns were contributing to patient
morbidity and mortality, as well as costs. (Feldman HI et al. 1996).
The United States Renal Data System (USRDS) reported that HD
access failure was the most frequent cause of hospitalization for patients
with CKD stage 5 and in some centers, it accounted for the largest
number of hospital days Studies also indicated a decreasing interval
between placement of a vascular access and a surgical procedure needed
to restore patency with significant costs to restore patency (USRDS
annual report 2013)
Aggressive monitoring of hemodynamics within an AVG or AV
fistula (AVF) to detect access dysfunction may reduce the rate of
thrombosis (NK/DOQI Clinical Practice Guideline [CPG] 4). Thus, much
access-related morbidity and associated costs might be avoided. The
number of interventions required to maintain access patency may be
decreased further by the use of fistulae rather than AVGs. The National
Kidney Foundation (NKF) issued the Kidney Disease Outcomes Quality
Initiative (KDOQI) clinical practice guidelines (CPGs) for Vascular
Access in an effort to improve patient survival and quality of life (QOL),
reduce morbidity, and increase efficiency of care. Vascular access
patency and adequate HD are essential to the optimal management of HD
patients with CKD stage 5. The first is a necessary prerequisite for the
second. To improve quality of life (QOL) and overall outcomes for HD
patients, two primary goals were originally put forth in the vascular
access guidelines to emphasis placement of a functioning fistula.
(DOQI Clinical Practice Guidelines for Vascular Access, 1997):
• Increase the placement of native fistulae
• Detect access dysfunction before access thrombosis.
The Centers for Medicare & Medicaid Services (CMS) has actively
collected data on three Clinical Performance Measures (CPMs) derived from
the original and revised KDOQI Guidelines for Vascular Access. The failure
to ―adequately‖ increase the number of fistulae among either incident or
prevalent HD patients during the past 6 years (Centers for Medicare & Medicaid
Services: 2013 Annual Report) or to reduce the use of catheters led to a CMS
mandate that the ESRD networks develop Quality Improvement Projects
(QIPs) on Vascular Access. These have been distilled into three key points:
avoid central catheterization, thus avoiding loss of central patency; maintain
existing access by detecting impending failure, followed by prompt
intervention; and maximize creation of fistulae as the best long-term access.
Out of these concepts has grown the National Vascular Access Improvement
Initiative (NVAII), emphasizing a fistula first approach.
A number of barriers need to be overcome to achieve the goals set
for vascular fistula construction; chief among these is the late referral of
patients for permanent access placement, reflected in patient
hospitalizations. In some regions, up to 73% of patients are hospitalized
for initiation of HD therapy, almost invariably for dialysis catheter access
placement. Unexpectedly, the modest increases in fistula use rates have
been accompanied by increases in the use of catheters. (Centers for
Medicare & Medicaid Services: 2013 Annual Report)
Early referral of patients with CKD stage 5 is absolutely
essential to allow for access planning and thus increase the probability of
fistula construction and maturation, thereby decreasing the need for
catheter placement (Steven F. et al 2012)
Angio-access classification (Akingba A. 2011)
Years after the initial efforts to create the appropriate vascular
access in order to perform a safe hemodialysis, modern nephrologists
have now the possibility to select the appropriate access for their patients.
Thus, the first distinction is made between temporary and permanent VA.
Temporary VA with expected half-life less than 90 days,
peripheral arteriovenous shunts and non cuffed double lumen catheters
are included.
Mid-term VA with expected half-life from 3 months to 3 years
include veno-venous accesses (tunneled cuffed catheters and port catheter
devices) and arteriovenous internal shunts, requiring vascular graft
synthetic (PTFE) or biologic (saphenous vein, Procol, etc.) material ,or
external shunt.
Long-term VA with an expected half-life more than 3 years
includes virtually the native arteriovenous fistulas and the new generation
of PTFE grafts.
1. Acute hemodialysis vascular access
Urgent hemodialysis requires immediate vascular access with the
ease of insertion and availability for immediate use. Two types of such
accesses are currently available: non-tunnelled dialysis catheters and
cuffed, tunnelled dialysis catheters. Double-lumen, non-cuffed, non-
tunnelled hemodialysis catheters are the preferred method for immediate
hemodialysis when a long-term access is not available .Central veins such
as jugular which is suitable for two to three weeks of use, subclavian or
femoral, can be used as insertion routes of these catheters Nowadays, the
subclavian catheters should be generally avoided because of the high
incidence of vein stenosis and thrombosis. Femoral catheters are usually
used for a single treatment (ambulatory patients) or for three to seven
days in bed bound patients (US Patent 2011)
However, the KDOQI guidelines suggest that non-cuffed, non
tunnelled catheters should be used for less than one week. Tunnelled
catheters should be placed for those who require dialysis for longer than
one week. Infections are the principal reason for catheter removal.
2. Permanent vascular access
Taking patient factors into consideration, such as life expectancy,
comorbidities, the status of the venous and arterial vascular system, is
very important in order to prescribe the appropriate access. In 2002 the
American Association for Vascular Surgery and the Society for Vascular
Surgery published reporting standards according to which three essential
components of VA should be mentioned: conduit (autogenous,
prosthetic), location and configuration (strait, looped, direct, etc.)
(Reinhold C. et al 2011)
a. Arteriovenous fistula:
An AVF is the preferred type of vascular access; it has the lowest
complication rates for thrombosis (one-sixth of AVGs) and infection
(one-tenth of AVGs). (Clemente N. et al 2014)
There are 3 types of AVFs:
position, either with a side-to-side or a side-artery-to-vein-end
anastomosis.
end-to-side fashion to either bridge a larger anatomical distance, or to
bring the vein to the surface where it is accessible for cannulation and
requires a tunnel to position the vein in its new location.
location and is connected to an artery and vein in end-to-end fashion.
Both second and third types require the formation of a tunnel
(Hentschel, 2008).
End-to-end anastomoses are now rarely performed, since
complete disruption of the artery imposes a risk for peripheral ischemia
and thrombosis. The most common surgical technique is the side-to-end
anastomosis (Hentschel, 2008). Fistula size and flow increase over time of
8–12 weeks with initial blood flow rates ranging from 200 to 300
mL/min.
Creating the AVF well before it is required for dialysis allows for
this process to take place in an adequate fashion prior to use. NKF-
K/DOQI guideline 8 suggest that the patient be referred for the creation
of an AVF when the patient’s creatine clearance is at 25 mL/min or less,
their serum creatine is 4 mg/dL or more, or within 1 year of anticipated
need (NKF-K/DOQI Clinical Practice Guidelines For Vascular Access).
Proper patient selection will enhance the opportunity to place an
AVF. Any physical evidence (scars) that the patient has had previous
central venous catheters should be documented. In most instances a
patient will give a positive history for such an occurrence, but this is not
always the case (Charmaine E. et al 2013).
The patient’s chest, breast and upper arms should be evaluated for
the presence of swelling or collateral veins. In patients with normal
venous pressure, central venous occlusion may not be associated with
swelling; however, the presence of collateral veins should alert the
examiner to the problem.
In the creation of an AVF both the artery and vein are important
and specially directed evaluations of both must be completed.
In relation to the arterial system, two issues are important. The
vessel must be capable of delivering blood flow at a rate adequate to
support dialysis and the utilization of the vessel for the creation of an
access must not jeopardize the viability of the digits and hand. Arterial
narrowing and calcification are relatively common in ESRD patients,
especially those who are diabetic and hypertensive. This problem can
usually be diagnosed before the patient is sent for surgery. Optimally,
three things relative to the arterial system (Table 2) should be present for
the creation of an AVF (Dominico S. et al 2014 ).
Firstly, the patient should have less than 20 mmHg differential in
blood pressure between the two arms; a greater difference suggests the
presence of arterial disease that should be evaluated before access
placement. Secondly, the palmar arch should be patent. The palmar arch
can be tested for patency using the Allen test. Use of vascular Doppler
can increase the effectiveness of the Allen test in predicting collateral
arterial perfusion of the hand (Reinhold C.et al. 2011)
And thirdly, the arterial lumen should be 2 mm or greater in
diameter at the point proposed for the anastomosis. This can best be
determined using color flow Doppler.
Table 2 - Arterial
Requirements for AVF
Pressure differential < 20 mmHg between arms
Patent palmar arch
Arterial lumen diameter 2.0 mm or greater at point of anastomosis
Venous anatomy is extremely important for access creation. If
there is a vascular problem that is going to interfere with the creation of
an AVF it is more likely to be venous than arterial. The cephalic vein is
ideal for an AVF because it is located on ventral surface of the forearm
and the lateral surface of the upper arm. These features make for easy
access in the dialysis facility with the patient in a sitting position.
Venous mapping should be performed in all patients prior to the
placement of an access. Routine preoperative mapping results in a
marked increase in placement of AV fistulas, as well as an improvement
in the adequacy of forearm fistulas for dialysis (Reinhold C.et al. 2011)
The primary goal of venous mapping is to identify a cephalic vein
that is suitable for the creation of an arteriovenous fistula. Basically, there
are three methods for doing venous mapping – physical examination,
ultrasound and by angiography.
It is essential that the patient be evaluated with outflow
obstruction so as to dilate the veins of the arm adequately regardless of
the method used for mapping. For physical examination, this is best done
using a blood pressure cuff inflated to a pressure about 5 mm Hg above
diastolic pressure. This should be left in place for periods of no more than
5 minutes at a time. In many patients, venous anatomy can be evaluated
very well by this approach.
However, most surgeons will want a more detailed venogram
performed using either color flow Doppler ultrasound or angiography
prior to surgery. Color flow Doppler ultrasound is considered to be the
best method for visualizing the venous anatomy primarily because it
avoids the use of radio contrast. Optimum features on venogram are
shown in (Table 3) (Silva MB et al, 1998).
Table 3 – Venous Requirements for AVF
Luminal diameter 2.5 mm or greater at anastomosis point
Absence of obstruction
Straight segment for cannulation
Within 1 cm of surface
Continuity with proximal central veins
First accessory vein at least 5 cm from the anastomosis
In instances in which venous mapping cannot be done by
ultrasound or if the technique is not available, equivalent results can be
obtained by angiography.
Kidney Disease Outcomes Quality Initiative (KDOQI) Vascular
Access guidelines, suggest that a working AVF should have a blood flow
>600 mL/min, a diameter >0.6 cm, and be at a depth of 0.6 cm
(between0.5 and 1.0 cm) from the surface, 6 weeks after its creation.
In fistulas that are successfully maturing, flow increases rapidly
post-surgery, from baseline values of 30–50 mL/min to 200–800 mL/min
within 1 week, generally reaching flows >480 mL/min at 8 weeks
(Malovrh M, 1998).
The AVFs must be evaluated 4–6 weeks after placement, and
experienced examiners (e.g. dialysis nurses) can identify non-maturing
fistulas with 80% accuracy (Nabil J. et al 2015).
b. Arteriovenous graft
AVGs were the most commonly used type of dialysis access in
the U.S. However, they do not last as long as AVFs and they have higher
rates of infection and thrombosis (USRDS, 2007 Annual Data Report. 2007).
Grafts present a second choice of VA when AVF is not able to be
performed because of vascular problems. AVGs can be cannulated about
2-3 weeks after placement, although there are studies suggesting that
immediate assessment after placement for PTFE AVGs is possible (Schild
A. et al, 2011).
c. Tunneled hemodialysis catheter
TCs are used when AVFs or AVGs are not possible to be created
for several reasons such as multiple vascular surgeries, which lead to
vascular thrombosis, or when patients have severe peripheral vascular
disease or very low cardiac output. Studies have revealed that central
venous catheters are colonized within 10 days of placement; however,
colonization of the catheter biofilm does not correspond to positive blood
cultures or clinical signs of bacteremia (Power A. et al 2011).
When conventional venous accesses have been exhausted and
peritoneal dialysis is impossible, it is mandatory to use alternative
procedures for VA in order to continue HD. Trans-lumbar inferior vena
cava central venous catheters (CVCs) belong to this category and it seems
that they can offer relatively safe and effective long-term HD access
(Power A et al, 2011).
Hemodialysis vascular access in children
The choice of replacement therapy in children is variable. The
registry of the North American Pediatric Renal Trials and Collaborative
Studies (NAPRTCS) reports that of patients initiating renal replacement
therapy in pediatric canters ( NAPRTCS. NAPRTCS: 2011 Annual Report.
2011): one quarter of children underwent preemptive renal transplantation,
one half were started on peritoneal dialysis and one quarter were started
on hemodialysis.
Kidney transplantation remains the preferred therapy for pediatric
patients. Therefore, many of them receive maintenance HD through an
indwelling catheter in perspective of short HD period (USRDS, 2007).
However, hemodialysis can be performed successfully in infants
and very young children, as well. Proper evaluation prior to choice of
hemodialysis access is mandatory. The use of an AV fistula, which is the
recommended type of vascular access in adults, is limited in children due
to the size of their vessels. In the 2008 NAPRTCS annual report, vascular
access for hemodialysis included external percutaneous catheter in 78%
of patients, internal AV fistula in 12%, and internal and external AV
shunt in 7.3 and 0.7 %, respectively (NAPRTCS. NAPRTCS: 2011 Annual
Report. 2011).
K/DOQI has encouraged greater use of AV fistulas in larger
children receiving hemodialysis who are not likely to receive a transplant
within 12 months, with a goal of achieving more effective dialysis with
fewer complications than the ones occurring with catheters.
Vascular access complications and survival
Studies have shown a mortality risk dependent on access type,
with the highest risk associated with central venous dialysis catheters,
followed by AVGs and then AVFs. Additionally, patients who had a
catheter as first VA, had more complications and higher mortality (El
Minshawy et al, 2004). Same results have been presented by Ng LJ (2011) et
al who examined hospitalization burden related to VA type among 2635
incident patients.
KDOQI Concluded guidelines for treatment of fistula
complications Guideline five:
5.1 Problems developing in the early period after AVF
construction (first 6 months) should be promptly addressed.
5.1.1 Persistent swelling of the hand or arm should be
expeditiously evaluated and the underlying pathology should
be corrected.
5.1.2 A program should be in place to detect early access
dysfunction, particularly delays in maturation. The patient
should be evaluated no later than 6 weeks after access
placement.
5.2 Intervention: Intervention on a fistula should be performed for
the presence of:
5.2.1 Inadequate flow to support the prescribed dialysis blood
flow.
5.2.2 Hemo-dynamically significant venous stenosis.
5.2.3 Aneurysm formation in a primary fistula. Post-
aneurysmal stenosis that drives aneurysm also should be
corrected. The aneurysmal segment should not be cannulated.
5.2.4 Ischemia in the access arm.
5.3 Indications for pre-emptive PTA:
A fistula with a greater than 50% stenosis in either the venous
outflow or arterial inflow, in conjunction with clinical or
physiological abnormalities, should be treated with PTA or surgical
revision.
5.3.1 Abnormalities include reduction in flow, increase in static
pressures, access recirculation preempting adequate delivery of
dialysis, or abnormal physical findings.
5.4 Stenosis, as well as the clinical parameters used to detect it,
should return to within acceptable limits following intervention.
5.5 Thrombectomy of a fistula should be attempted as early as
possible after thrombosis is detected, but can be successful even after
several days.
5.6 Access evaluation for ischemia:
5.6.1 Patients with an AVF should be assessed on a regular
basis for possible ischemia.
5.6.2 Patients with new findings of ischemia should be referred
to a vascular access surgeon emergently.
5.7 Infections of primary AVFs are rare and should be treated as
sub-acute bacterial endocarditis with 6 weeks of antibiotic therapy.
Fistula surgical excision should be performed in cases of septic emboli.
Final remarks and conclusions
The radiocephalic and the brachiobasilic AVF are the two types of
VA with the longest duration of function, although a high rate of initial
failure is seen with the radiocephalic AV fistula (Rodriguez JA et al, 2000). It
is the preferred VA on account of the longest duration, its low
complications rates and its ease of puncture (Kinnaert P et al, 1977, Reilly
DT, 1982, Windus DW, 1993).
Age, female gender, presence of diabetic nephropathy, start of
dialysis with a catheter and failure to wait for initial maturation of the VA
are risk factors and account for the majority of VA failures during renal
replacement therapy (RRT). Repeated VA failure has been identified as a
risk factor for mortality (de Almeida E et al, 1997).
The brachiocephalic AV fistula is the preferred type of VA, if the
radiocephalic approach fails. In case of diabetic patients this seems to be
the primary fistula if adequate vessels are not available, this is a frequent
finding. Four year permeability rates of 80% have been reported (Bender
MH et al, 1994).
The effort to create fistula first, has successfully increased the
prevalence of AVFs (Beasley C et al, 2004). However, the number of TCs
has also increased, and those placed for bridging a patient to a functional
AVF may stay in place longer (USRDS, 2007 Annual Data Report. 2007).
Studies about fistula placement success from the US and European
countries differ, significantly in the primary patency rate of AVFs at one
year. US studies including diabetic patients, report lower patency rates
(40%–43%). Konner et al (2002) reports a primary patency rate in diabetic
patients of 69%–81%, depending on gender and age (results reported
from 748 AVFs over 5 years). Chemla et al performed 552 AVFs in 4
years, achieving a primary patency rate at 22 months of 80% in 153
patients with radio-cephalic fistulas (Fassiadis N et al, 2007). These data
state that the lower mortality of these patients with AVF, may be due to
factors beyond VA associated infections and dysfunctions. However, data
from 1996 to 2006 collected from Dialysis Outcomes and Practice
Patterns Study (DOPPS) indicate a growing use of catheters in many
countries (Rayner HC and RL Pisoni, 2010). Also, data in 2011 shows
increased patency for TCs in female gender patients.
In new dialysis patients, early referral to a nephrologist and early
patient education strongly predict a successful functioning permanent VA
at dialysis initiation and it also seems that the patients have better
metabolic and clinical situation at the beginning of HD, lower long-term
morbidity and higher survival for the first two years (Sesso R and MM
Yoshihiro, 1997, Arora P et al, 1999, Stehman-Breen CO et al, 2000, Pena JM et al,
2006).
AV fistula is better when used for the first hemodialysis
treatment compared to starting hemodialysis with a catheter (Pisoni RL et
al, 2002, Rayner HC et al, 2003, Ravani P et al, 2004). Graft is, however, a
better alternative than catheter for patients, where the creation of an
attempted AVF failed or could not be created for different reasons (Ethier
J et al, 2008).
In conclusion, arteriovenous fistula has to be the first choice in
vascular access when suitable vessels are available. Arteriovenous grafts
and Central Venous Catheters may be also a good alternative as first
choice when suitable vessels are not available or as a second choice when
there is AVF failure. Female gender and old patients are more likely to
start hemodialysis with a TC. Finally, a well matured vascular access is
important for long access survival and early referral to nephrologists is
mandatory.
DO’S AND DON’TS FOR AV FISTULAS (Henry LM, 2011)
This is a simple outline regarding some of the do’s and don’ts for
AV fistula creation. If one follows the do’s carefully, there are fewer
don’ts that are necessary.
Do have a plan. Decide on a programmatic view of
approaching the patient requiring vascular access, and follow it
routinely for consistent outcomes. Teach the patient and the dialysis
unit personnel the plan, so everyone is on the same page. Empower
the patient to help direct his/her care. Think ahead as one can
anticipate problems, and address them routinely.
Do start distally in the extremity, and with subsequent
needed procedures, utilize the plan. Know the anatomy completely,
such that each move is based on sound anatomic principles.
Understanding both the arterial and venous anatomy can avoid future
problems and help with future decision making.
Do utilize preoperative imaging, usually with venous
mapping with the duplex ultrasound technology.
Do have a plan which addresses the next step in the decision
making process, and do it prior to needing to make that decision.
Do choose the correct patients for fistula creation. Variables
that may dissuade one from proceeding blindly with a fistula include
the elderly, diabetic, female, and/or obese patient.
Do regard issues of choosing correct patients and the
technical issues as important parts of the decision tree.
Do consider secondary fistula creation in the patient with a
failing access, and think of this before the primary one has failed.
Utilize appropriate studies as necessary to help make choices for the
secondary fistula.
Do think one step ahead, always.
Don’t abandon a thrombosed fistula. Thrombectomy
and revision can create an access that will last for a long time.
Don’t injure veins in patients’ routine care. Protect
superficial and deep arm veins, as well as the central circulation, and
teach the non-ESRD caregivers about it.
Don’t forget about other options, as peritoneal dialysis
and transplantation are excellent choices in selected patients.
Attentions to some simple do’s and don’ts of fistula creation and
maintenance can help avoid issues with vascular access in our patients.
PHYSIOLOGY OF
ARTERIO-VENOUS
FISTULA
MATURATION
`
PHYSIOLOGY OF FISTULA MATURATION
Creation of an arteriovenous fistula bypasses resistance vessels
in the distal extremity and establishes a parallel, fixed, low-resistance
return pathway to the heart. Volume flow through the fistula increases as
a result of the reduced resistance. Loss of perfusion to other vascular beds
is prevented by a reflex increase in cardiac output that compensates for
the increased flow through the fistula and maintains blood pressure
(Konner K et al, 2003).
Adequate perfusion of the tissue in the extremity distal to the
fistula requires sufficient dilation of the arterial system proximal to the
fistula to compensate for the shunting of blood through the fistula. In
most patients, flow through the artery proximal to the fistula does not
increase sufficiently to meet the demands of the fixed shunt through the
fistula. In this case, retrograde flow in the artery distal to the fistula helps
feed the low-resistance shunt pathway but in the process steals blood flow
from the distal extremity. Stenosis or narrowing in the proximal artery
will exacerbate the distal steal. (Billet A et al, 1984, Ramuzat A, 2003).When
severe, this can lead to tissue ischemia and pain that may require fistula
ligation or a distal revascularization and interval ligation (DRIL)
procedure to restore distal tissue perfusion (Konner K et al, 2003).
Fistula maturation depends on obtaining sufficient flow through
the fistula to support hemodialysis and prevent thrombosis. Fistula flow
rate depends on the pressure gradient and the total resistance in the fistula
circuit including the proximal artery, fistula anastomosis, and the
downstream vein. Although much attention has focused on the
downstream vein, it is often forgotten that arterial blood flow must also
increase substantially for successful fistula maturation. Mean blood flow
in the brachial artery at rest is around 50 ml/min, whereas mean blood
flow in the radial artery at rest is typically less than 25 ml/min (Lomonte C
et al, 2005).
With exercise or reactive hyperemia brachial artery mean blood
flow can increase 3–5-fold. However, for a successful fistula mean blood
flow in the artery must increase by at least10–20-fold (to at least 500
ml/min). In order to accommodate this increase in blood flow, the artery
must dilate. Based on Pouseuille’s law, where blood flow (Q) is
proportional to the product of the pressure gradient (∆P) and vessel radius
(r) to the fourth power divided by the viscosity (η) of blood (Q α
∆P×r4/η), if blood flow is steady and the pressure gradient down the
artery as well as the blood viscosity are constant then the brachial artery
lumen would need to dilate by nearly 80% to achieve a 10-fold increase
in flow rate (10¼=1.78). In most studies, the actual measured increase in
radial or brachial artery diameter after creation of an arteriovenous fistula
is only 40–50% (Dammers R et al, 2005, Lomonte C et al, 2005). The difference
can be accounted for by several factors. First, arterial flow is pulsatile
rather than steady and the average pressure gradient is not fixed but
increases following fistula placement (Remuzzi A et al, 2003).
Before fistula creation, pulsatile flow in the brachial or radial
artery is ante grade for only part of each cardiac cycle and falls to zero or
below (i.e. retrograde flow) during diastole (Fig. 1).
Fig. 1. Overview of fistula maturation. The figure depicts the temporal pattern from top
to bottom of successful (left) and unsuccessful (right) fistula maturation in a
radiocephalic fistula. The top of the figure shows the preoperative flow and pressure in
the radial artery and cephalic vein. The inset shows the volume flow in the radial artery
through two cardiac cycles. Note that flow rate returns to zero during diastole. The
middle two figures depict the situation 1 day after fistula creation for a fistula that has
dilated rapidly and is likely to mature (left) or one that has not dilated sufficiently and is
likely to fail (right). The middle graph inset shows that after creation of the low-
resistance circuit, volume flow rate remains high and significantly above zero
throughout both systole and diastole. Thus, the mean volume flow rate is much greater
than predicted for the extent of arterial dilation by Pouseuille’s law. Note the turbulent
flow at the arteriovenous anastomosis creates resistance that drops venous pressure to
about a third of arterial pressure. The three figures at the bottom depict the situation at
4–8 weeks after fistula creation for a successful fistula (left) or two possible modes of
early fistula failure – the development of a juxta-anastomotic stenosis (middle) or
impaired dilation (right). Between 20 and 50% of radiocephalic fistulas will fail to
mature and between 65 and 100% will have evidence of a stenosis.(Dixon BS, 2006).
Following creation of the low-resistance fistula, flow in the
artery remains high and ante-grade throughout the cardiac cycle implying
that the average arterial pressure gradient following fistula creation has
increased (Remuzzi A et al, 2003). Hence, mean flow rate (the time-averaged
area under the flow curve) for a given artery diameter is much greater.
Second, blood viscosity decreases with increasing flow rate thus limiting
the increase in wall shear stress (WSS) (friction) for any given vessel
radius. Finally, as mentioned above and shown in Figure 1, retrograde
flow from the distal artery occurs in about 75% of forearm fistulas and
accounts for an average of 25% of the blood flow into the venous limb of
the fistula. Together, these factors limit the magnitude of the dilation in
the proximal artery that is required to achieve the necessary 10–20-fold
increase in flow rate. Nonetheless, substantial arterial dilation and
remodeling is still required for successful fistula maturation (Dammers R
et al, 2005)
Changes in pressure and flow are the stimulus for vascular
dilation and remodeling after fistula formation. Pressure and flow exert
their effect by causing deformation and thereby creating opposing
stresses within the vessel wall (Dobrin PB et al, 1988).
The deformations of the vessel occur in three directions:
Circumferential, radial and longitudinal. These deformations create both
normal (i.e. tensile or compressive) stress and shear (tangential) stress in
each of the three directions. Thus, there are a total of nine static
mechanical factors (three static deformations and six static stresses) that
may influence vascular dilation and remodeling. This is further
complicated by the fact that pressure and flow vary with time (i.e. are
pulsatile) and thus each of these nine factors also varies with time. This
makes it difficult to isolate and understand the exact contribution of each
mechanical factor to the process of vascular remodeling. Most studies
have focused on the role of only three factors, (longitudinal) shear stress,
circumferential deformation, and circumferential (tensile) stress. Dixon BS,
2006).
However, a study by Dobrin et al looked at the effect of nine of
the most likely mechanical factors (three static deformations, three static
stresses, pulsatile deformation and pulsatile stress each as an aggregate
single factor, and longitudinal WSS) on vascular remodeling in an
interposition vein graft. They found that intimal thickening correlated
with low WSS and medial thickening correlated with circumferential
deformation. A similar detailed analysis of mechanical factors
influencing arterial or venous dilation and remodeling after fistula
formation has not been performed. However, the study by Dobrin seems
to validate the central importance of longitudinal shear stress and
circumferential deformation and stress as the central mechanical factors
influencing vascular dilation and remodeling (Dobrin et al, 1988)
Based on experimental models and clinical studies, the major
stimulus for arterial vasodilation and remodeling after fistula formation is
the increase in blood flow velocity and attendant increase in WSS (Ben
Driss A et al, 1997). Shear stress is sensed by the endothelium and loss of
endothelial cells impairs arterial dilation, vascular remodeling, and
normalization of WSS after fistula formation (Tohda K et al, 1992).
The exact biophysical mechanism whereby endothelial cells
sense and transmit intracellular information about shear stress is
incompletely understood (Resnick N, et al., 2003).The increase in shear
stress leads to release of nitric oxide and other endothelium-dependent
vasodilators that dilate the artery and tend to restore shear stress back
towards baseline (Miller VM and Burnett Jr JC, 1992, Tronc F et al, 1996, Ben
Driss A et al, 1997).
Although substantial arterial dilation (24%) occurs immediately
upon fistula creation, further dilation is required over the subsequent days
and weeks to normalize arterial shear stress. In contrast to earlier reports,
a recent study by Dammers et al. (2005) found that despite substantial
arterial dilation, the increase in shear stress did not normalize even 1 year
after fistula creation. This suggests that arterial adaptation after fistula
creation may be incomplete. (Lomonte C et al, 2005),
The mechanistic steps leading to arterial dilation and remodeling
after fistula formation have not been completely elucidated. However, the
early rapid phase of arterial dilation is likely mediated by smooth muscle
relaxation in response to endothelial release of nitric oxide and other
vasodilator. By itself, this early vasorelaxation is not sufficient to
normalize arterial shear stress (Corpataux JM et al, 2002).
In experimental studies of fistula maturation, further
fragmentation of the elastic lamina is required for complete arterial
dilation and normalization of arterial shear stress. This fragmentation is
mediated by metalloproteases (MPs) and can be blocked by inhibitors of
nitric oxide synthase suggesting that metalloproteinase activation is under
the control of endothelial derived nitric oxide. Inhibitors of
metalloprotease activation or nitric oxide synthesis partially prevented the
arterial dilation and normalization of shear stress. (Tronc F et al, 2000).
Using a mouse carotid-jugular arterio-venous model, Castier et
al (2005) have further shown that both the increase in MP activity and
arterial dilation after fistula formation were completely lost in mice with
homozygous targeted deletion of endothelial nitric oxide synthase.
The study by Castier et al. (2005) further demonstrated the
importance of reactive oxygen species and peroxynitrite formation in
arterial remodeling. Arterial dilation and MP activation was significantly
attenuated after fistula creation in mice with deletion of the p47phox
subunit of nicotinamide adenine dinucleotide phosphate (reduced form)
oxidase. Moreover, peroxynitrite formation (as determined by
nitrotyrosine staining) was increased in the arterial wall after fistula
formation and this was blocked in endothelial nitric oxide synthase mice
and significantly attenuated in p47phox mice.
The increase in MP activity could be blocked by ebselen, an
inhibitor of reactive oxygen species. Taken together, these observations
suggest that increased shear stress after fistula formation stimulates both
an increase in arterial nitric oxide and reactive oxygen species that lead to
enhanced formation of peroxynitrite and activation of MPs required for
arterial remodeling.
Increases in both the mRNA and enzymatic activity of the
gelatinases, MP-2, and MP-9 have been detected in the artery after fistula
creation suggesting that these metalloproteinases may mediate the
observed fragmentation of the elastic lamina. (Castier Y et al, 2005).
However, in one study only increases in MP-2 but not MP-9 were
observed, suggesting that the effect of MP-2 may predominate. MP-9 is
reportedly more responsive to oscillatory rather than unidirectional shear
stress, which might account for a difference in arterial MP- 2 and MP-9
activation after fistula formation (Magid R et al, 2003). In addition to the
increase in MP-2 mRNA, an increase in posttranscriptional activation of
MP-2 has also been suggested to occur based on the observation that
mRNA for furin and the furin-activated proprotein convertase MT1-MMP
increase before the increase in MP-2 activity. It is important to note that
activation of MMPs has also been implicated in the development of
neointimal hyperplasia (NIH), which clearly would be detrimental to
arterial dilation and fistula maturation (Pasterkamp G et al, 2004). The
mechanism whereby MMP activation promotes expansive remodeling
over NIH is not known.
Interestingly, activation of the toll-like receptor (TLR) 4 is also
involved in an experimental model of expansive remodeling. Mice
lacking toll-like receptor 4 demonstrated defective expansive remodeling
associated with an increase in arterial collagen content suggesting that the
toll-like receptor 4 plays a role in collagen turnover required for arterial
remodeling (Hollestelle SC et al, 2004).
Further investigation is needed to better understand the
mechanism of expansive remodeling after fistula formation in
experimental models and to determine whether similar events occur after
fistula formation in humans. In experimental models of expansive
remodeling after fistula formation, the cross-sectional area of the arterial
wall increases following fistula creation, composed of increased elastin,
collagen, and possibly smooth muscle cell In human studies, no
measurable increase in wall cross-sectional area was found in the
proximal radial artery at 12 weeks after fistula formation. However, after
1 year the radial artery wall does appear to thicken, presumably in
response to the increased circumferential wall stress caused by arterial
dilation (Dammers R et al, 2005).This implies that remodeling of the radial
artery after fistula formation in humans acutely involves lumen dilation
but over time there is vessel wall thickening presumably associated with
cellular proliferation and an increase in overall matrix formation similar
to that seen in experimental models.
Venous dilation is the clinically more apparent process in fistula
maturation that ultimately determines fistula suitability. Vein dilation
occurs rapidly after fistula creation and continues over several weeks. In a
study by Wong et al. (1996) average luminal vein diameter increased by
56% 1 day after surgical creation and further increased to 123% of
control at 12 weeks in forearm fistulas that ultimately were successful for
hemodialysis. Similarly, Corpataux et al. (2002) found that vein lumen
increased by 86% at 1 week and 179% at 12 weeks compared to the
contralateral non-operated vein.
The increase in fistula blood flow follows a similar time course
with a rapid increase immediately following surgical anastomosis
followed by a gradual increase to maximal blood flow within 4–12 weeks
thereafter. (Lomonte C et al, 2005).
Although variation in the rate of blood flow increase does occur,
typically fistulas attain 40–60% of maximal blood flow within 1 day after
surgical anastomosis. (Remuzzi A et al, 2003, Lomonte C et al, 2005). Near-
maximal blood flow is achieved within 4 weeks in most forearm fistulas
(Lomonte C et al, 2005). These small single-center studies suggest that most
fistulas should be suitable for dialysis within 4 weeks and failure to attain
suitability by this time point is an indication for further evaluation (Asif A
et al, 2006). However, some fistulas take longer time to mature and further
investigation is needed to determine the optimal time to assess fistula
maturation.
Corpataux et al. (2002) examined the determinants of vein
dilation after fistula formation. Venous pressure increased immediately
after fistula creation but only to a mean pressure of about 30% of that
seen in the immediate upstream artery (49±19/24.5±6 vs.
151±14/92.4±11mm Hg in the artery. The large pressure drop was
attributed to increased resistance owing to energy loss from turbulent
blood flow at the anastomosis (documented clinically by the palpable
thrill present over the anastomosis).
The increase in luminal pressure mediates the rapid early vein
dilation. However, the vein still retained substantial compliance reserve
as demonstrated by preserved systolo-diastolic diameter changes that
were similar to or greater than those seen in the radial artery despite the
lower venous systolo-diastolic pressure pulse. Despite the early dilation,
the increased blood flow was associated with an increase in vein wall
shear stress (WSS) immediately after fistula formation. Over the next 12
weeks, calculated shear stress gradually decreased as vein luminal
diameter increased. This gradual increase in diameter occurred without a
further increase in venous pressure. Hence, it appears that increased
venous pressure accounts for the rapid early increase in vein diameter but
that the subsequent venous dilation is a response to normalize the flow-
induced increase in WSS. The biochemical mechanism that mediates
flow-induced dilation in veins has not been explored to the same extent as
in arteries (Dixon BS, 2006).
In clinical studies, using currently available techniques vein
wall thickness does not change measurably after fistula creation.
However, the substantial increase in vein diameter with a fixed wall
thickness leads to a marked increase in the calculated vein wall cross-
sectional area (Corpataux JM et al, 2002).This eccentric venous hypertrophy
is likely mediated by the increased circumferential wall distention or
stress that results from venous dilation and increased luminal pressure. In
an experimental aortocaval fistula model, histological evidence of venous
thickening was observed and characterized by NIH, smooth muscle cell
proliferation and increased extracellular matrix deposition. There was
also evidence of histological injury with early up-regulation of mRNA for
MCP-1, PAI-1, and endothelin-1 and later up-regulation of mRNA for the
fibrogenic cytokine, transforming growth factor-b. These changes are
similar to those seen in human veins used for arterial interposition grafts
(Nath KA et al, 2003)
The role of MMPs in venous remodeling of an arteriovenous
fistula has not been reported. In vein grafts exposed to arterial pressure
and flow, both MMP-2 and MMP-9 have been reported to increase
(Berceli SA et al, 2006).
However, the temporal change and cell-type-specific localization
of these MMPs was not consistent between the studies. Taken together,
these studies demonstrate that veins respond to increased pressure and
shear stress by activating genetic stress and injury programs leading to
venous wall hypertrophy associated with neointimal and medial
thickening ( Berceli SA et al, 2006).
PREDICTORS OF MATURATION
Several studies have looked at factors that might predict fistula
maturation. Preoperative vascular mapping has been shown to improve
the rate of fistula placement and overall surgical success rate (Robbin ML,
2002). However, surprisingly neither preoperative vein nor artery size has
been found to be uniformly reliable as a predictor of successful fistula
maturation into a suitable access (Lockhart ME et al, 2004).
Very small arteries (e.g. less than 1.6 mm) and veins will likely
fail (the exact cutoff likely depending on surgical experience and
expertise) but above this lower limit preoperative vessel size does not
accurately predict maturation. Preoperative measurement of venous
compliance was a predictor of subsequent fistula maturation in one study
but only a weak predictor of fistula maturation in two earlier studies (van
der Linden J et al, 2006)
On the other hand, several studies have shown that postoperative
flow rate measured by Doppler ultrasound in a forearm fistula is a
moderately good predictor of fistula maturation. These studies have
reported using a cut-off between 400 and 500 ml/min at 2–8 weeks as a
predictor of fistula maturation. (Asif A et al, 2006)
A clinical examination of the fistula may be as accurate as
Doppler flow measurements). However, the criteria for making a clinical
determination by physical examination have not been vigorously
established and tested. Collectively, these studies suggest that the
functional ability of the artery and vein to dilate and achieve a rapid
increase in blood flow after surgery may be the most important
determinant of fistula maturation. Consistent with this, a study by
Malovrh (1998) demonstrated that preoperative measurement of arterial
dilation in response to reactive hyperemia (generated after release of a fist
clenched for 2 min) could predict subsequent forearm fistula maturation.
A resistive index of less than 0.7 at reactive hyperemia had 95%
sensitivity, 61% specificity, and 87% positive predictive value for
predicting forearm fistula maturation. This observation was not
confirmed in a more recent study, but there appear to be differences in the
measurement techniques (use of velocity flow rate vs volume flow rate to
calculate resistive index) that might account for the difference (Lockhart
ME et al, 2004 ).
Other factors that have been reported to influence fistula
maturation include surgical experience, gender, and evidence of extensive
vascular disease (Miller CD et al, 2003).
The observation that women have poorer fistula maturation than
men has been frequently reported and assumed to be due to smaller vessel
size. However, two recent studies found no gender difference in
preoperative arterial or venous diameter Miller CD et al, 2003).
Despite equivalent preoperative vessel size, in one study
maturation was poorer in women but in the other study maturation rates
were equivalent. More work is needed on this interesting observation
(Caplin N et al, 2003).
ANATOMICAL CORRELATES OF IMPAIRED
MATURATION
When evaluated by angiography, most insufficient fistulas have
one or more anatomic lesions that underlie the impaired maturation
(Beathard GA et al, 2003). Correcting the lesions has been shown to improve
the overall rate of fistula maturation implying that the lesions are
functionally important (Beathard GA et al, 2003).
The most common finding is venous stenosis occurring in 65–
100% of angiographically evaluated failing fistulas. More than half of the
stenoses occur in the vein immediately downstream of the anastomosis
(juxta-anastomotic stenosis) and frequently involve the anastomosis itself.
Stenoses also occur further downstream in the proximal vein as well as
less frequently in the central vein or feeding artery. The presence of
accessory veins has also been reported to be an important, potentially
remediable contributor to poor fistula maturation in some studies
(Beathard GA et al, 2003).
The primary problem is not the accessory vein but the impaired
arterial and/or venous dilation that limits overall fistula flow. Shunting of
blood into accessory veins prevents sufficient flow developing in the
main cephalic vein to permit fistula dilation and maturation. Finally, in
one prospective controlled study, 35% of fistulas that did not mature had
no detectable lesion by angiography suggesting that failure of arterial
and/or venous dilation rather than stenosis was the predominant cause of
failure in this subgroup (Tordoir JH et al, 2003).
All of the single-center studies published have limitations
(Turmel-Rodrigues LA and Bourquelot P, 2003). Stenotic lesions may have
been missed owing to technical limitations in the prospective study by
Tordoir et al (2003) whereas referral bias may have increased the
prevalence of stenosis and accessory veins in the studies by Beathard et al
(2003) and Turmel-Rodrigues et al (2001).
Moreover, center-specific variations in the intensity of
preoperative vascular mapping or choice of vessels may influence the
frequency of seeing impaired dilation as a cause of impaired maturation.
Collectively, these studies imply that venous stenosis, impaired arterial
and venous dilation, and accessory veins account for most cases of
impaired fistula maturation but the exact frequency of each cause remains
uncertain.(Dixon BS, 2006).
OVERALL CARE OF
HEMODIALYSIS
PATIENT
OVERALL CARE OF HEMODIALYSIS PATIENT
The care of the ESRD patient can be represented by a square its
limbs are nephrologist, vascular surgeon, dialysis nurses and the institutes
which provide the dialysis machines, training of the medical personnel
and source of funding; Multidisciplinary teamwork (MDT).
However, in our practice, the most crucial aspect in the care of the
ESRD patient is the creation and preservation of a hemodialysis access
available every time the patient need a dialysis session, as the other
options for renal replacement therapy such as renal transplantation and
peritoneal dialysis are not available for every patient. Deprivation of the
ESRD patient from the dialysis session will lead to many complications
and may be fatal if it becomes prolonged. Thus; repeated failure of the
AV access is the biggest challenge and financial burden facing ESRD
patient care providers.
Care of the AV access:
1. Dialysis Outcome Quality Initiative; clinical practice guidelines
for vascular access:
As effort to control the cost and reduce the morbidity associated
with creation and preservation of vascular access, several initiatives are
being implemented by government agencies and private organization to
standardize the approach to the vascular access management. The
principle focus of these efforts is to change the practice pattern among
surgeons in the United States from primary placement of prosthetic AV
accesses to creation of autogenous AV accesses. The most influential of
these efforts is the National Kidney Foundation (NKF)/Dialysis
Outcome Quality Initiative (DOQI) guidelines, which were first
published in 1997 and most recently updated in 2006 (Vascular access
work group. 2006). The DOQI clinical practice guidelines for vascular
access were developed by multidisciplinary team of surgeons,
nephrologists, and dialysis nurses who evaluated the credibility of the
vascular access-related literature. They used the best available literature
to develop evidence-based clinical practice guidelines for vascular access.
In addition, for situations in which solid evidence was not available,
several clinical practice recommendations were adopted based on group
consensus.
The NKF/DOQI guidelines have emphasized the importance of the
autogenous AV access over the prosthetic grafts and defined an
autogenous access target of at least 50% of patients initiating dialysis and
an overall prevalence of 40% for all patients receiving hemodialysis
(NKF/DOQI 2007).
These guidelines have significantly influenced vascular access
practice in the United States; in the decade since these benchmarks were
established, the AV fistula creation and utilization rates have increased
markedly (David C. et al 2013).
As a movement in the United States to enhance autogenous AV
access utilization, many efforts have been spent to put strategies or
algorisms which emphasized the following principles for managing the
hemodialysis access in order: (David C. et al 2013).
1. Preoperative upper extremity vein assessment with duplex
ultrasonography.
2. Use of the cuffed dialysis catheter as a bridge to the autogenous AV
access maturation, but never as a substitute to it.
3. First, try to Use an autogenous AV access procedure such as
brachiocephalic, venous transposition whenever possible, if not, then
shift to synthetic bridge grafts.
4. Timely revision of failing autogenous AV accesses and thorough
reevaluation of the patient for autogenous AV access creation is
recommended before uncorrectable access failure occurs.
5. In general the most accepted arteriovenous combinations for
autogenous access creation in order are radio-cephalic, radio-basilic,
brachiocephalic, brachio-basilic, before using the prosthetic grafts.
Limitations of the NFK/DOQI guidelines:
Unfortunately, many have interpreted the DOQI guidelines to mean
that the significant advantages of an AV fistula over an AV graft almost
always justify attempts at AV fistula creation. Furthermore, many
consider the attainment of the DOQI guideline benchmark of 50% AV
fistula creation rate to be an ad hoc measure of vascular access quality.
Such a stance may be responsible for negative and unintended
consequences. At least one study has suggested that the AV fistula non-
maturation rate has increased since the publication of the DOQI
guidelines and a dramatic increase in the use of cuffed dialysis catheters
has occurred presumably a result of the use of the catheter as a bridge to
fistula maturation. Therefore, we must be cautious in using the DOQI
fistula creation bench mark putting in mind that the dialysis population is
not uniform and many factors influence AV fistula maturation in those
patients. (U.S. Renal Data System. 2013)
To date, the DOQI guidelines have neither made recommendations
regarding patient selection for specific AV access procedures nor
suggested a benchmark for primary failure rates of AV fistulae because to
do so ―might discourage AV fistula creation‖ (U.S. Renal Data System.
2013)
Indeed, further work is needed for evolution and implementation of
these guidelines in our practice to decrease the morbidity and improve the
quality of life of the growing population of patients with ESRD.
2. SVS and AAVS vascular access nomenclature:
The Committee on Reporting Standards of the Society of Vascular
Surgery (SVS) and the American Association for Vascular surgery
(AAVS) has published reporting standards for vascular access placement
and revision (Anton N. et al 2008). This document provides preferred
nomenclature for vascular access procedures and standardized methods
for reporting patency and complications. The adoption of these standards
should permit meaningful comparison of studies reporting the outcome of
vascular access procedures.
3. Recommended standards for management of hemodialysis access
(Anton N. et al 2008):
a. Preoperative optimization of the general condition of the patient as
correcting hypotension, anemia and controlling DM is mandatory
to provide the best chance for the AV access to mature and survive
as long as possible.
b. Selecting a patient for the most appropriate access is one of the
most challenging aspects of vascular access surgery because the
dialysis population is not uniform, and the early thrombosis or
failure of maturation of AV fistula can have significant adverse
effects, such as the need for prolonged use of cuffed dialysis
catheters and loss of potential AV access sites.
c. When feasible, and its maturation and preservation is expected, the
autogenous AV access is preferable over the prosthetic bridge grafts as
it has longer patency rates and carries less incidence of complications
specially infection. This can be confirmed by through clinical and
radiological evaluation of the patient.
d. For the autogenous AV access, it is recommended to start with distal
arteriovenous combinations to preserve the proximal ones for further
AV fistula creation when the distal access failed which is expected.
e. Meticulous intraoperative techniques and proper postoperative care is
needed to preserve the access as long as possible. Avoid early
puncture of the access until its maturation. Avoid puncture of the
superficial or deep veins in the upper limb used for the AV access
placement for any reason (sample withdrawal or IV drug
administration) which increases the risk of access thrombosis. Avoid
constricting dressing or cloths over the access. Putting proper
applicable surveillance and monitoring programs for early detection of
access dysfunction (stenosis, early infection, or early
pseudoaneurysm) and its management.
f. Putting an algorithm for every patient including the future plan of the
possible autogenous AV access creation; potential Autogenous
access configuration, prosthetic bridge graft placement and
temporary cuffed hemodialysis catheters insertion is mandatory from
the first time patient came to the vascular surgeon. This helps
markedly not to waste the potential access sites which end finally to
patients with failed access.
g. Conservative management of the postoperative access
complications including conservative surgeries aiming at
preservation of the access; access salvage should be attempted as
much as possible. For example the access aneurysm, pseudoaneurysm
and infection can be treated medically or by partial excision with
interposition graft; segmental bypass instead of total excision, also the
access thrombosis can be treated by thrombectomy either surgically or
by using the percutaneous techniques.
h. The systemic anticoagulants may be considered as a measure to
prevent early postoperative thrombosis especially in patients with
thrombophilia. Some studies presume that the use of the systemic
anticoagulants reduces the incidence of thrombosis and early failure of
the access.
i. Sufficient training of the medical personnel implicated in the care of
the ESRD patients including nephrologists, vascular surgeons, dialysis
nurses and harmonization the work and communication between them.
Also all the related government agencies and the private organizations
should provide every types of support for those patients.
j. Organization of the research work related to creation and preservation
of the AV access and management of its complications in order to put
standard protocols and recommendations aiming at decreasing the
incidence of repeated failure of the AV access and patients with failed
vascular access.
k. As a last resort, the tunneled dialysis catheters, lower extremity AV
access, chest wall and cervical bridge prosthetic grafts, peritoneal
dialysis and renal transplantation may be attempted to secure the
dialysis sessions and the renal replacement therapy for the patient.
MONITORING AND
SURVEILLANCE
Monitoring and surveillance
Adequate vascular access function is the most important
component determining the success or failure of hemodialysis therapy.
Access problems are a daily occurrence in busy dialysis units. Low blood
flow rates and loss of patency limit dialysis delivery extend treatment
times and result in under dialysis leading to increased morbidity and
mortality. Maintenance of adequate flow is the chief means of assuring
delivery of the prescribed dialysis dose. (Clemente N et al 2014).
Monitoring (M) is physical examination (inspection, palpation
and auscultation) of the vascular access to detect physical signs that
suggest the presence of dysfunction. In the United States, these basic
skills are not used. Rather there is a tendency to emphasize technology,
especially methodologies that are built in as ―elective‖ modules into the
dialysis delivery system. (Paulo T. et al 2014).
Surveillance (S) is periodic evaluation of the vascular access by
means of specialized tests that involve special instrumentation. Such tests
include access flow, access resistance, intra-access pressure both static
and dynamic and access recirculation. (Paulo T. et al 2014).
It is important to emphasize that surveillance and monitoring
(S/M) are complementary. Surveillance/monitoring using specific
assessments must be combined with regular assessment of clinical
parameters of the AVF and dialysis adequacy. These data should be
tabulated and tracked within each dialysis center as part of a quality
assurance and continuous quality improvement program (Lalathaksha K. et
al 2012).
The basic issue for vascular access monitoring and surveillance is
that stenoses develop over variable intervals in that great majority of
vascular accesses and, if detected and corrected, under dialysis can be
minimized or avoided and the rate of thrombosis can be reduced.
Prospective monitoring and surveillance can prolong access survival and
promote salvage through planning and co-ordination of efforts for
elective corrective intervention, rather than urgent procedures or
replacement. (Anatole B. et al 2012).
Many non-maturing AVFs can be salvaged using percutaneous
treatments that include angioplasty and obliteration of competing venous
collateral vessels. Best results are obtained when patients with
nonmaturing native fistulae are identified within 1-3 months of creation,
permitting referral of patients for fistulography and percutaneous salvage.
(Jariatul K., et al 2012).
Physical examination can be used as a monitoring tool to exclude
low flows associated with impending graft failures. There are 3
components to the access examination: inspection (look), palpation
(touch), and auscultation (listen). Simple inspection can reveal the
presence of aneurysms. A fistula that does not at least partially collapse
with arm elevation is likely to have an outflow stenosis. This logic
applies to the case in which a tourniquet does not appear necessary for
optimal cannulation. Strictures can be palpated and the intensity and
character of the bruits can suggest the location of stenosis. Downstream
stenosis also produces an overall dilation of the vein, giving it
―aneurysmal‖ proportions. (Anatole B. et al 2012).
If the physical examination does not clearly indicate the cause for
nonmaturation, both Doppler duplex ultrasonography (DDU) (with or
without color) or contrast fistulography (using dilute low-volume
injection) can be performed without risk of precipitating renal failure in
patients with advanced chronic kidney disease. (Jariatul K., et al 2012)
Invasive imaging
Standard, iodinated contrast is nephrotoxic and can potentially
hasten the need for dialysis among those patients not yet actively
dialyzing. The use of alternative contrast media, such as carbon dioxide
for venography or gadolinium for arteriography may avoid this potential
risk of dye associated renal injury (William P. et al 2013)
Non-invasive imaging
Lomonte et al (2005) used DDU to document the changes in blood
flow rate in the brachial artery following construction and maturation of a
radiocephalic wrist AVF in 18 incident uremic patients. The internal
diameter and blood flow rate of the brachial artery (QBA) at baseline
were 4.3 ± 0.7 mm and 56.1 ± 19.2 ml/min, respectively, and QBA
increased to 438.4 ± 86.0 ml/min at day 7, 720.4 ± 132.8 after AVF
construction in 17 of the AVFs. One failed to mature, with a flow of 88
ml/min at day 28. Thus the most rapid increases occur within the first
week (50% of maximum), with progressively smaller increases thereafter.
A similar technique of measuring brachial artery flow to assess
the relationship of QBA to intra-access pressure .Given that the brachial
artery flow is relatively easy to measure compared with that of the fistula
itself, this measure may be helpful in determining which AVFs will
probably fail. This screening should aid clinical assessment, thus
allowing sound judgment of the level of maturation of an AVF and of its
outcome. (William P. et al 2013).
In a properly operational program, asymptomatic but functionally
significant stenoses in AVFs are detected through a systematic S/M
program, referred for study, intervened upon and checked to verify that
the hemodynamics or functional abnormality has improved. A
functionally significant stenosis which is currently defined as a reduction
greater than 50% of normal vessel diameter that is accompanied by a
hemodynamic or clinical abnormality that interferes with the delivery of
dialysis, produce patient symptoms or impede AVF maturation is likely
to produce thrombosis within several months. (Louise M. et al 2013).
The basic tenet of vascular access monitoring and surveillance is
that stenosis develops over variable intervals in the great majority of
AVFs and if detected and corrected, maturation can be promoted, under-
dialysis minimized or avoided and thrombosis avoided or reduced. The
rationale for S/M depends on the ―dysfunction‖ hypothesis: AVF stenosis
reduces access flow and alters pressure profiles. An inflow stenosis either
prevents maturation of the AVF or in an established AVF, produces
dysfunction impairing the delivery of adequate dialysis and often
preceding thrombosis. The usefulness of flow or pressure surveillance
critically depends on the accuracy of the measurements themselves.
Unfortunately, both access flow and pressure vary in patients during and
more importantly between dialysis sessions. This arises from needle
rotation for cannulation and changes in hemodynamics among dialysis
sessions. (Charmaine L. et al 2013).
A single measurement is an inaccurate predictor of the presence
of stenosis. The only rational means to detect an evolving lesion is to
perform analysis using multiple repetitive measurements correlated with
clinical findings so that inappropriate referrals are not made. (Charmaine
L. et al 2013).
Crucial to the interpretation of any S/M technique is knowledge of
the ―best function‖ of the AVF with respect to intra-access flow and
pressure profile. The useable access flow, QA, resulting from this driving
force in turn depends on many variables: site of anastomosis (the arterial
diameter is larger proximally), presence or absence of disease in the
feeding artery, the patient’s ability to augment cardiac output in response
to the fistula, health of the vein and its ability to dilate and remodel and
the presence of tributaries. Development of stenosis in the AVF circuit
will either limit the initial flow increase or after maturation lead to a
progressive decrease in QA. Intra-access pressure will usually not
increase unless there is a downstream stenosis (as from a cephalic arch or
central vein stenosis). (Louise M. et al 2013).
It is important to emphasize that the quality and physical
dimensions of the artery and vein will determine the initial AVF function.
If the artery is healthy, the flow capacity of the AVF will be determined
by the characteristics of the vein used in access construction. Too small
vein will limit the flow. In general, arteries at more distal sites have less
capacity to deliver flow than more proximal sites. In general, forearm
radiocephalic AVFs have flows of 600- 1,000 ml/min, whereas elbow
level fistulas have flows of 1,000-2,000 ml/min. (William P. et al, 2013).
Some AVFs develop flow >3,000 ml/min and are associated with
cardiac decompensation. Use of calcified or atherosclerotic arteries will
yield a lower QA than those unaffected by such processes. Unfortunately,
arterial disease is not uncommon; access inflow stenosis occurs in one
third (and not the 5% that has been traditionally reported) of the graft
cases referred to interventional facilities with clinical evidence of venous
stenosis or thrombosis. This high rate is due to the aging of the population
and the progressive calcification of arteries that occurs in many patients
over years of dialysis. (Louise M. et al 2013)
Although nearly 70% of AVF showed stenosis in the body of the
fistula, stenosis in the feeding radial artery was found in 30.5% with a
mean degree of stenosis of 83.5% ± 15.8%. These patients tended to be
older (67.5 ± 11.5 years), and their AVF of longer vintage (48.9 ± 76.7
months) since they were on dialysis longer. The functional results of
elective surgery in radial artery stenosis were worse compared with those
in vein stenosis. (Louise M. et al 2013)
The relationship between QA and intra-access pressure in an AVF
as a stenosis develops depends on the location of lesions. If an outflow
stenosis develops and increases resistance, pressure will increase and
flow decrease. The increase in pressure will affect the post-needle
bleeding time and may contribute to aneurysmal dilation.
The frequency of measurements depends on the rate of
progression. With an inflow stenosis, venous pressures usually do not
change or decrease. However, such inflow lesions are usually easily
detected by physical examination because they occur in the first several
centimeters proximal to the anastomosis. Paradoxically, a high basal
intra-access pressure can occasionally be observed in an AVF in the
absence of stenosis, when the flow delivered by a healthy artery is in
excess of the venous system’s initial capacitance to accommodate to the
flow, because of all of the above confounders, there is little if any
correlation between a single measurement of flow and intra-access
pressure. Thus, serial repeated measurements of pressure or flow within
each patient’s AVF correlated with findings of routine physical
examination are more valuable in detecting a stenosis than any isolated
measurements of absolute intra-access pressure, normalized ratio or
access flow. (Louise M. et al 2013).
The utility of dynamic venous pressure (DVP) at flows of 150-
225 ml/min to predict presence of stenosis or occurrence of thrombosis is
quite limited .There are no direct studies of its sensitivity or specificity to
detect hemodynamically significant stenosis in AVFs. As a result, the
method is not currently recommended as a surveillance technique. By
contrast, flow measurements by a variety of techniques DDU assessment
for stenosis and static pressure measurements (direct or indirect) can
detect hemodynamically significant stenosis in native fistulae. (NKF-
K/DOQI guidelines updates, 2007).
If the prescribed Kt/V is consistently not delivered in a patient
who is using a native fistula, measurement of access recirculation, using
the recommended urea-based method or one of the non-urea methods
should be conducted. Recirculation is a relatively late predictor of access
dysfunction but because of other factors the test is less sensitive and less
specific for detecting low flow access dysfunction. Flow in AV fistulae,
unlike in AV grafts, can decrease to a level less than the prescribed blood
pump flow (i.e., less than 300 to 500 ml/min), while still maintaining
access patency. Thus measurement of recirculation is a more useful
screening tool in AV fistulae compared with AV grafts. (Charmaine L. et
al, 2013).
Flow measurements performed by dilution ultrasound and other
techniques can be done online during dialysis, providing rapid feedback.
The same applies for static pressures. Flow and pressure techniques can
be combined to provide even more hemodynamic information. Measuring
venous pressure is the least expensive method of surveillance for stenosis.
Online access flow measurements are available but require further
improvements. (Charmaine L. et al, 2013).
Predictors of access failure
1-Access volume flow: (Charmaine L. et al 2013)
Recent evidence suggests that detection of low access blood flow
rates is an early, sensitive and specific predictor for both venous stenosis
and subsequent thrombosis This concept is gaining increased acceptance
as time goes on. A major advantage of intra-access blood flow
measurement is that, in contrast to ―venous pressures‖, flow is affected by
stenosis irrespective of their location. Measurement of intra-access blood
flow was technically difficult until Doppler ultrasound is available.). It
can also be measured with a less expensive device, based on the Fick
principle, the so called ―ultrasound dilution technique‖ developed by
Krivitski.
Access blood flow less than 500mL/min in native AVF or less
than 800mL/min in prosthetic grafts is associated with stenosis greater
than 50% in cross section and a progressively higher risk of thrombosis in
the ensuing three months. Sequential monitoring of blood flow is
potentially even more than 25% was associated with a relative thrombosis
risk in accesses without a decrement in blood flow. A 50% decrease in
blood flow resulted in a 30fold increase in relative risk of thrombosis to
these not having a decrease in blood flow.
Rapid drop in blood flow may need study for the anatomical
structure. The high predictive value of a drop in intra-access blood flow
for thrombosis has two major implications: the first is that the degree of
venous stenosis is often progressive, and a significant drop in blood flow
(20 to 30%) carries higher relative risk of thrombosis than a low flow by
itself. This is consistent with flow dynamics across constriction whereby
flow is maintained until a critical stenosis is reached, and afterwards flow
is progressively reduced. The second implication is that a serial
measurement of access blood flow provides sufficient early warning of
the ―criticality‖ of the stenosis so that intervention may be helpful.
2-Access pressure: (Louise M. et al 2013)
Schwab et al proposed monitoring the venous pressure during
dialysis as a non invasive method for detecting the formation of stenosis
at the venous anastomosis of AV graft. Refinements to the method of
measurement of these intra-access ―venous‖ pressures have been
proposed by Besarab and Van Stone. However, the physiologic principle
upon which such measurement was advocated (that is distal ―venous‖
stenosis results in elevation of hemodynamic pressure proximal to the
stenosis) may not apply to a large number of accesses. The stenosis at
sites other than the venous anastomosis attenuates the usefulness of
―venous‖ pressure monitoring as a predictive measure of access failures.
Several additional methods for the detection of incipient
prosthetic graft failures have been advocated, ranging from the
measurement of venous pressures under static (zero dialyzer flow)
conditions. Measurements of access recirculation, acute decrements of
dialysis dose, or ―negative‖ arterial pressures that develop as the pump
speed exceeds the blood flow that can be obtained from the access.
However, while ―venous‖ pressures or measures of recirculation
or negative arterial pressures may be useful, they are often late
manifestations of access failure.
3-peak systolic velocity ratio:
Peak systolic velocity >2 indicates presence of significant
stenosis.
Modalities for detection of access stenosis
(Tordoir M., Rooijens P. 2012)
1-Color Doppler ultrasonography (CDUS):
CDUS is a readily available, inexpensive, and non invasive
method. It directly visualizes the degree of stenosis and also measure the
flow.
For sonographic assessment of stenosis the vascular access is
examined in longitudinal and transverse plane from the feeding brachial
artery across the anastomosis and the arterialised draining vein as far into
the central venous system as possible. The perivascular space is also
investigated because functional stenosis may be the result of extra-
luminal compression of the access by hematoma or seroma.
Drawbacks of CDUS are the inaccurate detection of central
venous obstruction and that the quality of the images depends on the
skills of the operator.
2- Digital subtraction angiography (DSA):
Currently, (DSA) is the gold standard for the evaluation of access
patency. DSA is no more invasive than needle puncture for dialysis and
can be combined with endovascular intervention. However, DSA exposes
the patient to ionizing radiation and iodinated contrast agents that may
cause a deterioration of residual renal function or allergic reaction.
3- Contrast-enhanced magnetic resonance angiography (CE-
MRA):
Recently, (CE-MRA) has been introduced for the evaluation of
failing access fistulas and grafts. CE-MRA is a non invasive, lacks
ionizing radiation, and provides an angiographic map of the complete
vascular tree of an access. A major limitation is the absence of CE-MRA
guided access intervention.
4- Multi-slice computed tomographic angiography (MSCTA):
MSCTA is a good non invasive diagnostic technique to detect
various hemodialysis vascular access abnormalities. It is more
economical than DSA and could replace DSA in the imaging of
hemodialysis vascular access and provide important information for
further AVF-revising surgery or PTA..
ACCESS
DYSFUNCTION AND
COMPLICATIONS
Access dysfunction and complications
A successful functioning vascular access is the ―lifeline‖ for a
hemodialysis patient. Hemodialysis vascular access dysfunction is a
major cause of morbidity and mortality in hemodialysis patients (Collins
AJ et al, 2009).
Improving vascular access outcomes remains an ongoing
challenge for nephrologists, vascular access surgeons, and
interventionists. In arteriovenous fistulas (AVF) and grafts (AVG), the
most common cause of this vascular access dysfunction is venous
stenosis as a result of neointimal hyperplasia within the peri-anastomotic
region (AVF) or at the graft-vein anastomosis (AVG) (Clemente N et al
2014).
There have been few effective treatments to-date for venous
neointimal hyperplasia in part because of the poor understanding of the
pathogenesis of venous neointimal hyperplasia. Central venous catheters
(CVC) are prone to frequent thrombosis and infection and the treatment
of catheter-related bacteremia (CRB) remains on ongoing debate
(Clemente N et al 2014)
Epidemiology of hemodialysis vascular access
Due to reduced AVF use and increased AVG (70% in 1993)
and catheter use in the United States from the mid-1980’s-1990’s, the
National Kidney Foundation in 2007, in an effort to improve vascular
access outcomes, published the first Kidney Disease Outcome Quality
Initiative (K/DOQI) clinical practice guidelines for vascular access to
optimize the care of vascular access in hemodialysis patients using
evidenced and opinion-based guidelines (2007).Since these initial clinical
practice guidelines have been published, we have seen the creation of the
Fistula First Breakthrough Initiative (FFBI) (Lok CE, 2011) and two more
revised K/DOQI clinical practice guidelines and performance measures
for vascular access (Clinical Practice Guidelines for Vascular Access, 2007)
which have clearly impacted and improved hemodialysis vascular access
management.
The most recent report from the 2013 United States Renal Data
System (USRDS) has showed an AVF prevalence of 50% a marked
improvement since 2004 (39% AVF prevalence), 2000 (30% AVF
prevalence), and 1998 (26% AVF prevalence) in the United States. In
contrast, AVF prevalence in Europe and Japan, reported from the Dialysis
Outcomes and Practice Patterns Study (DOPPS) has been historically
much higher, ranging from 57-91% (USRDS 2013 Annual Data Report)
While the K/DOQI guidelines and FFBI have clearly played an
instrumental role in meeting the initial target goal of 50% AVF
prevalence (new goal 66%)), the prevalence of CVC use continues to
remain between 20-30% in the United States (Fistula First National Access
Improvements Initiative, 2011).
Furthermore, this trend of increased catheter use has also been
observed in Europe. This is likely due to an increase in the number of
AVFs that have failed to mature for dialysis use in recent years (Paulo T. et
al 2014)
Clinical significance and economic implications of
hemodialysis vascular access dysfunction
When patients develop vascular access dysfunction, due to an
immature AVF or thrombosed AVF or AVG, they are often consigned to
CVC use for prolonged periods. Dialysis with a catheter is associated
with increased morbidity and mortality CVC use has significant clinical
implications such as increased risk of bacteremia which has been reported
to occur at a frequency ranging from 2.5 to 5.5 episodes per 1000-
catheterdays increased risk of 1-year mortality and 60-70% higher risk of
subsequent AVF failure (Venessa F. et al 2014)
Pathology and pathophysiologic mechanisms of
hemodialysis vascular access dysfunction
Pathology of Hemodialysis Vascular Access Stenosis in AVF and AVG
Venous stenosis that occurs in both AVFs and AVGs is
primarily due to neointimal hyperplasia. Venous stenosis in AVGs most
frequently arises from the development of aggressive neointimal
hyperplasia, characterized by (a) the presence of alpha smooth muscle
actin positive cells myofibroblasts, and microvessels within the
neointima, (b) an abundance of extracellular matrix components, (c)
angiogenesis (neovascularization) within the neointima and adventitia, (d)
a macrophage layer lining the perigraft region, and (e) an increased
expression of mediators and inflammatory cytokines such as TGF-β,
PDGF, and endothelin within the media, neointima and adventitia (Roy-
Chaudhury P et al, 2009).
While the neointimal hyperplasia in AVFs is similar to AVGs
in regards to pathogenesis, the venous stenosis that develops in AVFs is
highly influenced by the capacity of the vein to vasodilitate and vascular
injury from surgical technique (Roy-Chaudhury P, 2009).
In AVFs the two main etiologies of failure are an initial failure
to mature (non-maturation) and a subsequent (late) venous stenosis.
Similar to AVGs, venous neointimal hyperplasia in late AVF stenosis has
been shown to be composed primarily of alpha smooth muscle actin
positive cells, together with expression of mediators and cytokines such
as TGF-β, PDGF, and endothelin within the media and intima of the vein.
However, recently, the lesion of AVF non-maturation at 6 weeks after
AVF creation has also been described to have significant neointimal
hyperplasia (Roy-Chaudhury P, 2009).
PATHOGENESIS OF AV FISTULA FAILURE
Demographic and clinical factors
A number of clinical studies have attempted to identify risk
factors for AV fistula failure. Thus Miller et al have shown that
increasing age, female gender and the presence of diabetes were
associated with a poorer prognosis for forearm AV fistulae. Lok et al
looked specifically at maturation failure and found that Caucasian race,
increasing age and the presence of peripheral and coronary vascular
disease were predictive of these early failures. AV fistula success has also
been associated with the skills of the operating surgeon, suggesting that
issues such as vessel handling, torsion, kinking and the degree of
endothelial injury play an important role in AV fistula failure (Ernandez T
et al, 2006).
More recently, Van der Linden et al have shown that patients
with greater preoperative venous distensibility measured by
plethysmography tended to have a better chance of successful maturation.
This suggests that vessel quality and/or a baseline genetic predisposition
for flow-mediated dilatation could play an important role in the
development of a successful AV fistula. Finally, although it has been
shown that very small vessels (arterial sizes of less than 1.6 mm and
venous diameters of less than 2.5 mm) are associated with poor success
rates, there is surprisingly no continuous correlation between larger vessel
diameters and better AV fistula survival (Dixon BS, 2006). This suggests
that it could be the ability of the vessel to dilate, rather than the initial
vessel size that determines AV fistula success.
The pathogenesis of venous neointimal hyperplasia in AVG
stenosis and late AVF stenosis has been well described and is commonly
divided into upstream and downstream events (Roy-Chaudhury P et al,
2009).
Upstream events are characterized as the initial events and
insults that are responsible for endothelial and smooth muscle cell injury,
which leads to a cascade of mediators (downstream events) that regulate
oxidative stress, endothelial dysfunction, and inflammation (eventually
resulting in venous neointimal hyperplasia). Upstream events that are
believed to contribute to the pathogenesis of neointimal hyperplasia
include:
(1) surgical trauma at the time of AV surgery, (2) hemodynamic shear
stress at the vein-artery or vein-graft anastomosis, (3) bio-incompatibility
of the AVG, (4) vessel injury due to dialysis needle punctures, (5) uremia
resulting in endothelial dysfunction, and (6) repeated angioplasties
causing further endothelial injury. Downstream events represent the
response to endothelial (vascular) injury from the upstream events,
resulting in the migration of smooth muscle cells from the media to the
intima and eventually the development of neointimal hyperplasia (Roy-
Chaudhury P, 2009).
The pathogenesis in AVFs that fail to mature (early failure) for
dialysis, in contrast to AVG and late AVF failure, remains poorly
understood. At a histological level early AVF failure is also characterized
by aggressive neointimal hyperplasia in both animal and human models,
seen as early as 1 month in animals and 3 months in humans (Roy-
Chaudhury P et al, 2009).
The underlying factors (upstream events) which may contribute
to early AVF failure include (Lee T et al, 2011):
(1) small diameter sizes in the vein and artery, (2) surgical
injury at the time AV fistula placement, (3) previous venipunctures, (4)
development of accessory veins after surgery, (5) hemodynamic shear
stress at the AV anastomosis, (6) a genetic predisposition to vascular
constriction and neointimal hyperplasia, and (7) pre-existing venous
neointimal hyperplasia.
Upstream events
Abnormal hemodynamic shear stress profiles
High levels of laminar shear stress tend to be associated in
experimental models with appropriate vascular dilatation and a relative
lack of neointimal hyperplasia. This is probably as a result of endothelial
quiescence, high levels of nitric oxide release and low levels of
inflammatory cytokines. In contrast, low shear stress values, especially in
the context of oscillatory shear stress, tend to be associated with a lack of
vascular dilatation and an increase in neointimal hyperplasia. This is
probably as a result of endothelial activation, low levels of nitric oxide
and the release of inflammatory mediators that predispose to vascular
stenosis. AV fistulae failure could be due to the presence of a ―bad‖
hemodynamic profile following access surgery: i.e. regions of low flow
and oscillatory shear stress within the venous segment. Such a
hemodynamic profile could result not only in aggressive neointimal
hyperplasia but also in a failure of venous dilatation. In this context, it is
important to emphasize that the final amount of luminal stenosis in an AV
fistula is determined by the balance between the amount of vascular
dilatation or constriction and the amount of neointimal hyperplasia and
medial thickening. Thus even a very significant amount of neointimal
hyperplasia and medial hypertrophy will not result in luminal stenosis in
the presence of adequate dilatation. In contrast; even a small amount of
intimal hyperplasia and medial hypertrophy can cause a tight stenosis in
the absence of venous dilatation (Fig. 2).
Fig. 2. Vascular remodeling: The degree of luminal stenosis is dependent upon
both the magnitude of neointimal hyperplasia and the degree of vasodilatation or
vasoconstriction. With the same amount of neointimal hyperplasia, vascular
constriction (a) results in luminal stenosis, while vasodilatation (b) prevents the
occurrence of luminal stenosis. A similar situation is described in (c, d), where
the white area is the lumen. The area in black is the neointimal, which is
bordered on the outside by the internal elastic lamina and on the inside by the
lumen. The hatched area comprises the adventitia and the media. Note that the
luminal (white) area in both (c) and (d) are identical, despite (d) having much
less neointimal (black area). The reason for this is vasoconstriction in (d), which
has resulted in a decrease in the area enclosed by the internal elastic lamina. This
latter parameter is a good indicator of the amount of vascular or adventitial
remodeling. (Roy-Chaudhury P et al, 2009).
Other upstream injury pathways
While hemodynamic shear stress is likely to be the most
important upstream factor responsible for AV fistula failure, other factors
such as surgical injury and insertion of dialysis needles. needle
infiltrations, are also likely to play a role. In addition to direct
injury/infiltration, it has been shown that dialysis needles can result in an
increase in turbulence up to 4 cm downstream of the site of needle
placement (Lee T et al, 2006)
Finally, even though angioplasty is a treatment for AV fistula
stenosis, the actual procedure can cause significant endothelial and
smooth muscle cell injury which could result in an exacerbation of the
restenotic lesion. In support of this hypothesis, Chang et al (2004) have
demonstrated increased cellular proliferation and a shorter time to
stenosis in AV fistulae subjected to an angioplasty compared with those
with a primary stenosis.
Regardless of which form of upstream injury has the most
significance, it is believed that aggressive efforts to limit these different
types of injury could result in the development of novel therapies for AV
fistula failure.
Some of these approaches could include (a) identification of an
optimal anatomical configuration for AV fistula placement which
generates a ―good‖ hemodynamic profile, (b) the design of better dialysis
needles that cause less injury and turbulence (c), evidence-based
guidelines for performing angioplasty on failing fistulae and (d)
minimization of angioplasty and surgical injury through the local
application of anti-proliferative or pro-dilatory agents.
Downstream events
Paradigms for neointimal hyperplasia
Medial origin for neointimal cells (traditional paradigm)
Endothelial and smooth muscle injury results in the migration
of smooth muscle cells and myofibroblasts from the media into the
intima, where they proliferate and form the lesion of venous neointimal
hyperplasia. This process is orchestrated by a large number of mediators
including the cell cycle regulators, cytokines, chemokines, vasoactive
molecules and adhesion molecules (Chang CJ et al, 2005).
Adventitial origin for neointimal cells
Recent studies have demonstrated that fibroblasts migrate from
the adventitia, through the media and into the intima, where they acquire
the phenotype of myofibroblasts and contribute to final neointimal
volume (Roy-Chaudhury P, 2009)
Bone marrow origin for neointimal cells
Recent data also suggest a role for bone marrow–derived
smooth muscle progenitor cells in the pathogenesis of neointimal
hyperplasia. (Sata et al, 2002).
Endothelial progenitor cells and vascular repair
In addition to promoting angiogenesis, an important role of
EPCs which are bone marrow derived cells is rapid endothelialization of
regions of vascular injury (Fig. 3) (Roy-Chaudhury P, 2009).
Fig. 3. Endothelial progenitor cells: Endothelial progenitor cells (EPCs) are produced in
the bone marrow and can be mobilized by a number of different factors including
granulocyte colony–stimulating factor. This is a diagrammatic representation of EPCs
binding to injured endothelium in order to possibly prevent vasospasm, thrombosis and
neointimal hyperplasia. EC = endothelial cell. Adapted with permission from (4) (Roy-
Chaudhury P, Sukhatme VP, Cheung AK. Hemodialysis vascular access dysfunction: a
cellular and molecular viewpoint. J Am Soc Nephrol 2006; 17: 1112-27).
For example, the infusion of EPCs in the setting of angioplasty
or surgical graft placement results in enhanced endothelialization, which
translates into a reduction in neointimal hyperplasia (Roy-Chaudhury P,
2009).
Most importantly, there are a number of agents that can
enhance the mobilization of EPCs from the bone marrow (statins,
erythropoietin, granulocyte colony-stimulating factor and MMP-9).
Whether or not EPCs play a role in AV fistula success or failure is
unknown at the present time(Roy-Chaudhury P, 2009).
Oxidative stress
Many of the upstream mechanisms above (particularly
hemodynamic shear stress and angioplasty injury) have been documented
to result in an increased production of free radicals and its downstream
products nitrotyrosine and latter (peroxynitrate). The latter is a potent
upregulator of the matrix metalloproteinases (MMPs) (Dixon BS, 2006).
MMPs are key enzymes that cause breakdown of extracellular
matrix proteins such as collagen and elastin which facilitate the migration
of vascular smooth muscle cells (VSMCs) in neointimal hyperplasia
formation (Roy-Chaudhury P, 2009).
Clinical studies of stenotic and thrombotic AVGs and AVFs
have also demonstrated an upregulation of MMPs, and have documented
the co-localization of oxidative stress markers with inflammatory
cytokines such as transforming growth factor-beta (TGF-β), and platelet-
derived growth factor (PDGF), within the neointima of both stenotic
AVGs and AVFs (Misra S et al, 2008).
Heme-oxygenase-1 (HO-1) is an important enzyme pathway
which has been shown to confer protective effects in the vascular
endothelium and other organ systems through its anti-inflammatory,
antioxidant, or antiproliferative actions and properties (Roy-Chaudhury P,
2009).
Endothelial dysfunction in uremia
Uremic patients are more likely to respond to local or systemic
interventions that improve endothelial function which corresponds to
published data which demonstrate that antioxidants are successful in
reducing cardiovascular events in hemodialysis patients (with high
baseline levels of oxidative stress but not in non-uremic individuals
(Misra S et al, 2008)
Preexisting vascular abnormalities (Roy-Chaudhury P, 2009).
Uremic patients tend to have increased vascular stiffness which
could be due to increased deposition of collagenous material, and also the
impact of vascular calcification.
In addition, Kim et al have documented that intimal thickening
in the radial artery prior to surgical creation of AV fistulae correlates with
poorer fistula survival.
Genetic polymorphisms
The response to injury that results in neointimal hyperplasia
and AV fistula failure has been shown to be linked to genetic
polymorphisms for methylene tetrahydrofolate reductase, TGF- and
heme-oxygenase-1 gene products. (Lin CC et al, 2006)
Prognostic Factors Influencing the Patency of
Hemodialysis Vascular Access
(Clemente N. S., Paulo T., Vanessa F., Ferreira D 2014)
Medical Factors Contributing to Malfunction of HD Vascular Access
As shown in Table 3, several medical factors have been
attributed vascular access stenosis in HD patients
Stasis
Any cause of lower blood flow may predispose the vascular
access to stasis, which is an important component of Virchow’s triad.
Hypotension
Regardless of the cause of hypotension, it results in a reduction
in access flow, making it more susceptible to thrombosis.
Hypoalbuminemia
Hypoalbuminemia is related to a higher rate of thrombosis in
PTFE AVG .
Compression
Inappropriate compression of the vascular access after HD or
by accident during sleep.
Hypercoagulable states
Antiphospholipid antibodies
Antiphospholipid antibodies include lupus anticoagulant which
is associated with access thrombosis and anticardiolipin antibodies which
is associated with recurrent thrombosis.
Hyper-homocysteinemia
The common risk factor for both deep venous thrombosis and
atherosclerosis is homocysteine, which might cause endothelial
dysfunction, leading to impaired thrombolytic capacity and vasodilation
of vascular endothelium and increased vascular smooth muscle cell
(VSMC) proliferation
Factor V leiden
A mutation of the factor V gene leads to the formation of factor
V leiden, which was associated with peripheral vascular graft thrombosis.
Lipoprotein (a)
Association of lipoprotein (a) with athero-thrombotic
complications was reported in both the general and ESRD populations
Endothelial cell injury
Preexisting intimal hyperplasia
An important cause of inadequate radial artery diameter, and
histologically it is quite common in patients undergoing HD. Only
diabetes and age are risk factors for preexisting intimal hyperplasia.
Tumor necrosis factor-α (TNF-α)
Leukocytes release TNF-α, which could induce proliferation of
vascular smooth muscles leading to subsequent intimal hyperplasia. The
interaction between PTFE AVGs and circulating peripheral blood
mononuclear cells located upstream of the venous anastomosis
potentiates the release of TNF-α (Mattana J et al, 1997).
Oxidative stress
Oxidative hyperactivity in the uremic status usually leads to an
increased amount of circulating and tissue inflammatory molecules
Calcium phosphate deposition
Stenosis of AVFs was associated with calcium phosphate
deposition, which is mainly in the form of calcium apatite. Brushite,
another calcium phosphate precipitate, may be found in stenotic AVFs,
but it was not present in non-stenotic AVFs and normal veins (non-AVF)
Activated platelets
Injury to endothelial cells exposes the basement membrane and
extracellular matrix leading to activation of platelets. Inhibition of platelet
activation with aspirin and sulfinpyrazone has been shown to prevent
recurrent access thrombosis
Medications
The largest study evaluating the effects of specific medications
on AV access patency is the Dialysis Outcomes and Practice Patterns
Study (DOPPS). The primary patency of AVFs was not improved by any
drug, and only angiotensin converting enzyme inhibitors improved
secondary patency. Calcium channel blockers improved primary patency
of AVGs through inhibition of neointimal hyperplasia, and aspirin
improved secondary patency. Warfarin reduced primary graft patency,
although this may be due to deficiency of protein C or S. Another study
showed that dipyridamole alone was associated with a significant risk
reduction for AVG thrombosis, while aspirin did not improve the risk of
thrombosis
Red blood cell mass
The incidence of vascular access thrombosis was significantly
increased in patients receiving erythropoietin
Exercise
It's reported that an isometric exercise training program could
increase the diameter of the cephalic vein, theoretically increasing the
possibility of creation of an AVF.
Timely referral
Timely referral to nephrologists enables more precise
prediction of the appropriate timing for the placement of a fistula or graft
and the initiation of dialysis, which could help HD patients, avoid any
temporary catheter access.
Infection
About 50% of vascular access infections are caused by
Staphylococcus epidermidis, with Gram-negative organisms accounting
for approximately 23%
Cardiovascular risk factors
Smoking, a risk factor for atherosclerosis in general, is
associated with both early and late fistula failure. Diabetes has also
consistently been associated with access failure in prospective studies,
possibly due to an increase in VSMC proliferation.
Genotype Polymorphisms and AVF Malfunction
Transforming growth factor-b1 (TGF-b1)
Intimal hyperplasia, VSMC proliferation in the media with
subsequent migration to intima are mediated by several growth factors
such as TGF-β1.).
MTHFR
The odds ratio of genetic polymorphisms predicting AVF
malfunction is 1.77 for T allele-containing genotypes of MTHFR.
Heme-oxygenase-1 (HO-1)
HO-1 is another factor associated with higher risk of
developing some vascular diseases. HO-1 induction stimulates cell cycle
progression and proliferation in vascular endothelium , but inhibits the
growth of VSMCs via the release of CO.
Table 4: Prognostic factors affecting patency of vascular access
Mechanical factors
Surgical skill
Technique of puncture of vascular access
Shear stress on the vascular endothelia
Medical factors
Stasis: hypotension, Hypoalbuminemia, compression
Hypercoagulable states: antiphospholipid antibodies,
hyperhomocysteinemia, factor v Leiden, lipoprotein(a)
Endothelial cell injury: preexisting intimal hyperplasia,TNF-α,
oxidative stress, calcium phosphate deposition, activated platelets
Medications:ACEI(↑2º patency in AVF), CCB(↑1º patency in
AVG),Aspirin(↑2º patency in AVG), Dipyridamole (↑ AVG patency),
warfarin(↓1º patency in AVG)
Genotype polymorphism with poor patency of AVF:
TGF-β1:high producer haplotypes(+869/+915: TC/GG and TT/GG)
MTHFR:T allele of MTHFR C677T
HO-1:a longer length polymorphism with GT repeat number≥30
Lower access flow:<500mL/min for AVF, <600mL/min for AVG
Others: higher RBCs mass, less exercise, late referral, infection,
DM, smoking
Physical therapy: far infra-red therapy
TNF-α=tumor necrosis factor-α, ACEI=angiotensin converting enzyme inhibitor, 1º=primary,
2º=secondary, CCB=calcium channel blocker , TGF-β1=transforming growth factor β1,
MTHFR:methylene tetrahydrofolate reductase, HO-1=heme oxygenase-1, RBC=red blood cell,
DM=diabetes mellitus
(Table 4) prognostic factors affecting patency of hemodialysis vascular access
(Clemente N. et al 2014)
Therapies in hemodialysis vascular access dysfunction:
from the bench to bedside (Haskal ZJ et al, 2010)
There are currently few if any effective therapies to treat
hemodialysis vascular access stenosis and neointimal hyperplasia.
1. Systemic therapies
In an AVG study, dipyridamole and aspirin modestly reduced
the risk of stenosis and improved primary unassisted patency In the AVF
study clopidogrel reduced frequency of early thrombosis but did not
improve AVF suitability defined as cannulation with two needles,
minimum dialysis blood flow of 300ml/min, successful use 8/12 dialysis
sessions, and use after 120 days from creation
2. Radiation therapy
Radiation therapy has antiproliferative effects and potential
beneficial effects of vascular remodeling.
3. Far infrared therapy
In the lone clinical study of far infrared in dialysis access in
AVFs, patients who received far infrared therapy had improved access
flow and longer unassisted patencies through improving skin blood flow
and endothelial function.
4. Local drug delivery systems for hemodialysis access
Local drugs can be applied easily during surgery targeting the
adventitia and can diffuse rapidly through all layers of vessel wall with
minimal systemic toxicity.
a. Drug eluting paclitaxel perivascular wraps
Experimental studies have previously demonstrated the efficacy
of paclitaxel eluting wraps in AVG stenosis likely due to anti-
proliferative effects. However, there is incidence of infection. An
alternative approach is the use of sirolimus eluting COLL-R® wraps
(Covalon Technologies Ltd: Mississauga, Ontario, Canada)..
b. Endothelial cell loaded gel foam wraps
Initial experimental studies have documented a beneficial effect
of endothelial cell loaded gel-foam wraps in porcine models of AV fistula
and graft stenosis due to production of mediators that reduce thrombosis,
stenosis and increase intraluminal diameter.
c. Vascular Endothelial Growth Factor D (VEGF-D) gene therapy
The delivery of adenoviral particles encoding for vascular-
endothelial growth factor D to the site of vascular injury has been shown
to trigger the release of nitric oxide and prostacyclin and reduce
neointimal hyperplasia.
d. Recombinant elastase PRT-201
PRT-201 (Proteon Therapeutics; Waltham, MA) is a
recombinant pancreatic elastase topically applied at the outflow vein at
the time of surgery access creation resulting in both arterial and venous
dilation and increased AVF blood flow in experimental models.
5. Endovascular stent therapy (Haskal ZJ et al, 2010)
Endovascular vascular therapies (angioplasty or angioplasty
with stent placement) remain the only true intervention available to treat
vascular stenosis. The main advantage of stent therapy after angioplasty
is a reduction in adverse remodeling. In dialysis access, placement of bare
metal stents after angioplasty compared to angioplasty alone has been
shown to improve primary patency. However, bare-metal stents have
yielded poor results due to aggressive development of in-stent restenosis.
Stent grafts (covered stents constructed from the same material
of AVGs) have received recent attention as a therapy for prevention of
restenosis due to its ability to prevent elastic recoil and inability of the
neointimal cells to penetrate the covered barrier. This is the only
treatment to date that has shown to be effective to treat vascular access
stenosis in a large, randomized, clinical trial.
6. Improving hemodynamics (Haskal ZJ et al, 2010)
Altering the sheer stress pattern to prevent turbulent, low flow,
and low-sheer stresses could reduce the development of neointimal
hyperplasia.
Results from a newly developed anastomotic implant device,
―OptiflowTM‖ (Bioconnect Systems; Ambler, PA), to connect the artery
and vein in AVFs and improve hemodynamics by providing a symmetric
flow pattern, have shown a primary patency of 83% at 90 days
Complications of AVF
(Fistula First National Access Improvements Initiative, FFBI, 2011)
Although the AVF is associated with fewer complications
than are seen with other types of vascular access, they do occur and they
should be dealt with effectively. We categorize the major complications
that are seen in conjunction with arteriovenous fistulas under the headings
of early failure, late failure, excessive flow, aneurysm formation and
infection. Both early and late failures have multiple causes.
Table 5 – Causes of Early Fistula
Failure
Early AVF Failure
A fistula that is never usable for dialysis or that fails within
three months of use should be classified as an early failure. The
distinction between early and late failure is made because there are
certain unique lesions that are seen in the early category. Unfortunately,
these unique lesions are also major causes of late failure because they
were not diagnosed and corrected during the early period. The causes of
early failure can be classified as either inflow or outflow problems (Table
4). It is important to realize that most of the problems of both types can
be obviated by proper patient evaluation prior to an attempt at access
creation. (FFBI, 2011).
Inflow Problems Resulting In Early Failure
Inflow problems:
Pre-existing arterial anomalies
Anatomically small
Atherosclerotic disease
Acquired
Juxta-anastomotic stenosis
Outflow problems:
Pre-existing venous anomalies
Anatomically small
Fibrotic vein (stenotic)
Accessory veins (side branches)
For an AVF to develop and function adequately for
hemodialysis there must be good blood inflow. Both maturation and
adequacy of flow are dependent upon pressure and volume of flow.
Abnormalities of the feeding artery can result in early failure of the
access. Anomalies such as an artery that is too small for the creation of a
functional access and the presence of arterial disease such as
atherosclerosis can prevent the development of an adequate AVF or result
in its early demise. However, both of these problems should be
preventable by proper patient evaluation prior to access placement.
Fig. 4. Juxta-anastomotic stenosis; R-radial artery, C-cephalic vien, S-area of
stenosis(FFBI, 2011).
The unique problem that results in early access failure due to
inflow difficulties is an acquired entity that is referred to as juxta-
anastomotic stenosis. This is a specific type of venous stenosis
characterized by a very typical appearance (Figure 4). This lesion occurs
in the segment of vein that is immediately adjacent to the anastomosis;
thus the term juxta-anastomotic
The etiology of this lesion (Figure 4) is not clear. However,
this is the segment of vein that is mobilized and manipulated by the
surgeon in creating the fistula. It may be related to stretching, torsion or
other types of trauma. This segment is often skeletonized in the process
of mobilizing it for the creation of the fistula. This causes a loss of the
vasa venosum, which supplies blood to the vein. The effect of the lesion
is to obstruct fistula inflow. Since it occurs early, it results in early access
failure. This lesion is amenable to treatment. It can generally be
successfully treated by percutaneous angioplasty or surgically It is
important to realize that Juxta-anastomotic stenosis can be easily
diagnosed by physical examination
Outflow Problems Resulting in Early Failure
For an AVF to develop and function adequately for
hemodialysis there must also be adequate, low resistance blood outflow.
The absence of good out flow can result in failure of the access.
Anomalies that lead to outflow problems include veins that are too small
for fistula development, veins that are fibrotic or stenotic due to past
trauma such as venipuncture and the presence of accessory veins. The
first two of these should be preventable by proper patient evaluation prior
to access placement. Frequently, the presence of accessory veins is
recognized and dealt with by the surgeon at the time of fistula creation;
however, this is not always the case. In addition it must be remembered
that all of the veins receiving the drainage from the newly created
anastomosis enlarge. A small accessory vein may become enlarged with
time (Fistula First National Access Improvements Initiative, 2011).
Fig. 5a. Accessory vein; A – accessory vein, B – fistula. Fig. 5b. Collateral vein;
A – fistula, B – collateral (below stenosis), C –stenosis, D – accessory vein (above
stenosis), E – upper fistula
The optimum anatomy for the creation of a fistula is a single
vein without side branches. Unfortunately, this is not always the case.
The vein that is to become an AVF may have side branches. These side
branches, referred to as accessory veins (Figure 5a), are normal anatomy.
However, they must be distinguished from collateral veins (Figure 5b),
which are pathological anatomy and always associated with a
downstream (antegrade) stenosis. In ideal situations the presence of an
accessory vein may be viewed as an advantage, the patient may develop
an additional venous channel suitable for cannulation. However, under
less than optimal conditions, its presence can result in early AVF failure
(Haskal ZJ et al, 2010)
Fistula development is dependent upon flow and pressure.
Pressure necessary for fistula development is dependent upon the inflow
pressure and the upstream resistance of the draining vein. Downstream
(ante grade) resistance is decreased if the vessel branches because of the
increased effective cross-sectional diameter represented by multiple
vessels. Additionally, flow that should be limited to a single channel is
partitioned into two or more channels, each receiving less than the total.
Accessory veins may be single or multiple. It is important to
note that this anomaly can also be easily diagnosed by physical
examination (Beathard GA, 2002).
These veins can be ligated to convert the branched unusable
fistula into a functional AVF. Accessory veins along with juxta-
anastomotic stenosis represent the two most common causes of early
AVF failure in cases that have been properly evaluated prior to access
creation . These two lesions often occur together (Beathard GA, 2002).
Not all accessory veins need to be obliterated. The significance
of the additional venous structure can be judged by its size and apparent
blood flow. Small accessory veins seldom contribute significantly to the
fistula’s failure to develop. In general, an accessory vein that is less than
one-fourth the diameter of the main fistula is unlikely to prove to be
significant. Palpation of the upper fistula when the accessory vein is
manually occluded will also aid in determining the side branch’s
significance. If it is affecting the fistula, an apparent augmentation should
be evident when it is occluded.
If there is a downstream (ante grade) stenosis, the side branch is
either a collateral that has developed because of the stenosis or an
accessory (meaning that it is a normal venous structure) that is being
augmented by the presence of the stenosis. There is no way to distinguish
between these two possibilities. In any case, the significance of a side
branch associated with a downstream stenosis cannot be evaluated
adequately until the stenosis has been successfully treated. When
presented with the combination of a large side branch associated with a
downstream stenosis, the procedure that should be followed is to first
treat the stenosis and then determine the significance of the side branch.
In many instances it will be seen to have disappeared. (Fistula First
National Access Improvements Initiative, FFBI 2011).
Late Fistula Failure
Late fistula failure is defined as failure that occurs after 3
months. The primary causes of failure occurring at this time are venous
stenosis and acquired arterial lesions. These lesions are manifest as
pathological changes in the fistula from increased pressure, and decreased
flow leading to inadequate dialysis and eventually thrombosis. It is
important to realize that the lesions typical of early failure are also
commonly seen during this later period because they were not addressed
in a timely fashion. (FFBI, 2011).
Venous Stenosis
Fortunately, venous stenosis does not occur in AVFs with the
same degree of frequency as is seen with synthetic grafts. Nevertheless it
is the most common cause of late fistula loss. For this reason it is
important that each dialysis facility have in place an organized program
for the prospective diagnosis of venous stenosis (NKF-K/DOQI Clinical
Practice Guidelines for Vascular Access, 2007).
This program should consist of weekly monitoring (done by
physical examination) and regular surveillance (done using specific tests).
Unlike the case with grafts, venous stenosis associated with the AVF
generally develops more centrally at areas of vein bifurcation, pressure
points and in association with venous valves. The development of
collateral veins is frequent and often preserves flow in the access.
Prospective treatment of stenosis before thrombosis is
important and will materially prolong access survival. Percutaneous
angioplasty has come to be the treatment of choice for these lesions with
greater than 95% success rate Long-term primary patency rates have been
in the range of 84% at 3 months, 57% to 67% at 6 months and 35 to 51%
at one year Unlike the situation for dialysis Grafts, pressure and flow
measurements are not very sensitive for the detection of stenosis
associated with AVFs. Blood entering the venous system of the AVF can
return through multiple collateral veins originating peripheral to a
stenosis. This can decrease the degree of pressure elevation despite the
presence of a significant stenosis. Detection of recirculation on the other
hand is valuable for screening because most AVFs can maintain patency
at very low flow rates, less than those needed for dialysis. When the flow
in the AVF is less than that of the blood pump, recirculation
occurs(Haskal ZJ et al, 2010)
Thrombosis
Even though AVFs have one-sixth the thrombosis rate of grafts,
thrombosis is the most common mechanism for late fistula failures. This
problem is generally associated with some type of anatomic lesion in the
draining veins. Problems on the arterial side of the AVF have been
reported to account for 17% of AVF thrombosis (El Minsh et al 2004).
Early studies reported relatively poor results with the treatment
of thrombosed AVFs. However, recent reports have documented
excellent success Success in the treatment of thrombosed fistulas has
ranged from 88 to 94% in these recent reports. Long-term primary
patency has been reported in the range of 63 to 89% at 3 months, 52 to
74% at 6 months and 27 to 47% at one year.
These numbers are considerably better than those seen for treatment of
thrombosed grafts. (El Minsh et al 2004)
When referring to an AVF, thrombosis is actually only a
clinical diagnosis. Many ―thrombosed‖ fistulas contain very little or no
thrombus. The flow has either stopped or decreased to a level that is
undetectable clinically, but the fistula continues to be patent. Its patency
is preserved by the presence of small side branches and the fact that it is a
native vein. The problem is due to the presence of a severe anatomical
lesion – stenosis. Treatment of the anatomic lesion resolves the situation
and restores flow. Failures are due to an inability to resolve the
anatomical lesion.(Fistula First National Access Improvements Initiative, 2011).
MANAGEMENT OF
DYSFUNCTIONAL
FISTULAE
Endovascular management of dysfunctional arterio-
venous fistula
I-INTRODUCTION
Routine surveillance programs for the early detection of stenoses
are advocated by both American and European DOQI guidelines. If these
are put into practice and combined with elective angioplasty, they have
been shown to substantially reduce the number of thrombosis per patient
year. Also, the use of catheters, the duration of hospitalization, the
number of missed dialysis treatments and even the total cost of treatment
of thrombosis-related events for grafts can be substantially reduced by
aggressive access surveillance. (Aamir S. et al 2012)
The NKF-K/DOQI taskforce has suggested PTA as one of the
preferred treatments for vascular access stenosis (NKF-K/DOQI clinical
practice guidelines for vascular access, 2007). Compared with surgery, PTA
has several advantages. PTA is an outpatient procedure, which preserves
access sites and guarantees use of the access for dialysis immediately
after the treatment. Also even centrally located stenoses are accessible
with PTA.
Endovascular management results in reduced morbidity compared
to standard surgical therapy with less post-procedure pain and wound
edema. Endovascular management of the thrombosed or dysfunctional
hemodialysis access (EMDA) is usually performed on outpatient basis
with the patient returning home or to the dialysis unit for treatment.
Subsequently, if the clinical and hemodynamic parameters
become abnormal, the patient should undergo re-evaluation of the
vascular access to identify recurrent stenosis requiring additional
intervention (Clinical practice guidelines for vascular access, 2007).
Balloon assisted maturation of AVF
As the understanding necessary to promote maturation of failing
fistulas has evolved, the old ―watch-and-wait‖ approach to fistula
maturation has been replaced by early endovascular interventions over
abandonment and surgical revision. KDOQI guidelines support
evaluating fistulas for failure to mature if they are not usable at 6 to 8
weeks. More recently, accelerated maturation techniques including forced
balloon angioplasty maturation (BAM) of both arterial and venous
segments as long as 20 to 30 cm in length have been promoted to rapidly
facilitate AVF usage in as little as 2 to 6 weeks after the initial 6- to 8-
week waiting period. (Miller GA et al 2010)
II. DEFINITIONS (ACR–SIR PRACTICE GUIDELINE, 2013)
o Thrombosed hemodialysis access: an autogenous fistula or
prosthetic graft/biologic graft that contain occlusive thrombus and
have no significant blood flow. Thrombus may extend into the
runoff veins or inflow arteries. Autogenous fistulae, particularly
those with aneurysmal segments, may harbor significantly larger
amounts of thrombus than prosthetic grafts. The diagnosis of a
thrombosed access is most frequently made by physical
examination.
o Dysfunctional hemodialysis access: (a) an access that has a
hemodynamically significant stenosis and an abnormal
hemodynamic or clinical indicator, or (b) an autogenous fistula that
has failed to mature during an adequate time period, or (c) an
access that cannot be successfully punctured to perform dialysis.
o Functionally significant stenosis: an anatomically significant
stenosis (>50% reduction of normal vessel diameter) accompanied
by a hemodynamic or clinical abnormality such as:
1. Change in physical examination characteristics of the thrill.
2. Elevated venous pressures recorded during hemodialysis (static
and dynamic pressures) or measured within the vascular access during a
diagnostic study (static pressures).
3. Detection of decreased intra-access blood flow at dialysis.
4. Swollen extremity.
5. Unexplained reduction in dialysis kinetics.
6. Clinical parameters such as prolonged bleeding after needle
withdrawal, altered physical examination characteristics of vascular
access, or thrombosis.
7. Elevated negative arterial pre-pump pressures that prevent
increasing to acceptable blood flow.
8. Inability to puncture to perform hemodialysis.
9. Abnormal recirculation values (Clinical practice guidelines for
vascular access, 2007).
Note: Prospective trend analysis is more valuable than isolated
abnormalities in the above hemodynamic and clinical parameters.
Abnormalities should be persistent over time to prompt treatment of the
access.
Anatomically significant stenoses include:
1. Inflow problems
a. Stenosis of the inflow artery to the access.
b. Stenosis at the anastomotic site of an autogenous
fistula.
c. Stenosis at the juxta-anastomotic segment of an
Autogenous
fistula.
d. Stenosis at the arterial anastomosis of synthetic grafts.
2. Access problems
a. Stenosis of the hypertrophied venous segment of an
autogenous fistula.
b. Intra-graft stenosis within prosthetic grafts.
c. The great majority of anatomic causes are intrinsic to
the graft or vessel. Rarely, however, extrinsic compression can
contribute to access dysfunction (e.g., prosthetic graft kinking,
pseudoaneurysm compression of the access, or compression
from a peri-access hematoma).
3. Outflow problems
a. Stenoses of the venous runoff from the venous
anastomosis to the central veins.
b. Failure to mature. In the case of the autogenous fistula,
multiple venous runoff channels that divert blood flow away
from the primary outflow vein can prevent the development of a
hypertrophied outflow vein suitable for puncture (Clinical practice
guidelines for vascular access, 2007).
c. Venous anastomotic stenosis of prosthetic grafts.
d. Central vein stenosis that may occur following the
placement of a central venous catheter ipsilateral to the site of
the access. These can also be caused by fibrous bands,
clavicular fractures, pacemaker wires, etc.
Note: While over 90% of access thromboses and dysfunction are due to
underlying anatomic stenoses, a physiologic process such as low cardiac
output, post-dialysis hypotension, access site infection, dehydration, or a
hypercoagulable state can result in thrombosis of a prosthetic graft or
autogenous fistula in the absence of an anatomic cause, or have a
synergistic effect with an anatomic stenosis to accelerate failure of the
hemodialysis access.
o Fistulogram: a specific type of angiogram to evaluate an
autogenous fistula or prosthetic graft used as vascular access for
hemodialysis treatment. A fistulogram should include imaging the
entire vascular access circuit including the arterial anastomosis, the
fistula or graft, the runoff veins, the ipsilateral central veins, and
the superior/inferior vena cava. Oblique projections are often
needed to optimize visualization and characterization of arterial
and venous stenoses. Evaluation of the inflow arteries may be
necessary when hemodynamic indicators or clinical symptoms are
not explained by fistulography.
o Endovascular thrombus removal: the removal of occlusive
thrombus from within the graft or fistula, including the outflow
veins and inflow arteries to restore blood flow to the access.
Removal of thrombus may be accomplished by any of several
catheter-directed methods, such as thrombolysis, aspiration
thrombectomy, balloon thrombectomy, clot maceration, or
mechanical thrombectomy.
o Endovascular treatment of a stenosis: the restoration of an
acceptable luminal diameter to the segment (anatomic success) and
resolution of the functional abnormality (Clinical practice guidelines for
vascular access, 2006). The stenosis may be treated with balloon
angioplasty. In selected instances, stents, stent grafts, or cutting
balloons may be required to improve luminal dimensions or repair
a vascular injury. Prospective intervention is currently warranted
for anatomical stenoses found in hemodialysis accesses and
draining veins that also have an associated hemodynamic or
clinical abnormality (Clinical practice guidelines for vascular access, 2007).
o Anatomic success of a treated stenosis: restoration of luminal
diameter with less than a 30% residual diameter stenosis. For
treatment of thrombosed accesses, both restoration of flow and a
less than 30% residual diameter stenosis for any significant
underlying stenosis are required to report anatomic success.
However, several studies have reported that there is poor
correlation between the degree of stenosis and the rate of blood
flow through a prosthetic graft Depending on the rate of blood flow
through the vascular access and the location of the treated lesion, a
30% residual stenosis may be hemodynamically significant. (donad
L. et al, 2013).
o Clinical success: the resumption of normal hemodialysis for a
minimum of at least one session. After treatment of a stenosis,
clinical success is defined as the improvement of clinical and
hemodynamic parameters. After treatment of either a thrombosed
access or an access-related stenosis, a continuous palpable thrill
with minimal or no pulsatility extending from the arterial
anastomosis can be considered one indicator of clinical success.
Physical examination of the access has the advantage of being
easily performed in the interventional suite, unlike most of the
monitoring tests. (Stephen B. et al 2013)
o Hemodynamic success: the restoration of hemodynamic
parameters. Increase of volume flows to above predefined
threshold values or reduction of venous dialysis or static pressures
to below predefined threshold values can be considered evidence of
hemodynamic success. Blood flow rates are not universally
available in interventional suites or dialysis clinics but have been
correlated with degree of stenosis for a single lesion (Amin MZ et al,
2004).
o Procedural success: anatomic success and at least one indicator of
hemodynamic or clinical success (Sidawy AN et al, 2002, Gray RJ et al,
2003).
o Post-intervention primary patency (PP): uninterrupted patency
after intervention until the next access thrombosis or
reintervention. Primary patency ends with treatment of a lesion
anywhere within the access circuit, from the arterial inflow to the
superior vena cava-right atrial junction (Sidawy AN et al, 2002, Gray
RJ et al, 2003).
o Post-intervention assisted primary patency (APP): patency
following intervention until access thrombosis or a surgical
intervention that excludes the treated lesion from the access circuit.
Percutaneous treatments of restenosis or a new arterial or venous
outflow stenosis/occlusion (excluding access thrombosis) are
compatible with APP. APP ends with percutaneous
thrombolysis/thrombectomy or simple surgical thrombectomy
(Gray RJ et al, 2003).
o Post-intervention secondary patency (SP): patency until the access
is surgically declotted, revised, or abandoned because the patient
undergoes renal transplant, or is lost to follow-up, etc.
Thrombolysis and percutaneous thrombectomy are compatible with
secondary patency, as are multiple repetitive treatments (Gray RJ et
al, 2003).
o Cumulative patency rate (CP): the total time that the access
remains patent (regardless of the number of primary interventions
and/or thrombectomy) during the given time period. CP begins at
the time that the graft is first placed (Clinical practice guidelines for
vascular access, 2007).
o Post-intervention lesion patency: the interval following
intervention until the next reintervention at or adjacent to the
original treatment site or until the extremity is abandoned for
permanent access due to surgeon choice, transplant, loss of follow-
up, etc. Endovascular or surgical treatments of other lesions in the
access circuit and creation of a new prosthetic graft or autogenous
fistula that incorporates the original lesion into the access circuit
are compatible with lesion patency.
o Mature arteriovenous fistula: a fistula suitable for use when the
diameter of a vein is sufficient to allow successful cannulation 4 to
6 weeks after construction (Clinical practice guidelines for vascular access,
2007).
o Steal syndrome: ipsilateral extremity ischemia in the presence of a
functional graft or fistula. Etiologies include atherosclerotic arterial
stenosis diffuse disease in the native arteries of the extremity or
excessive blood flow through the fistula or graft. High flow fistulas
with 20% to 50% of the cardiac output shunted through the access
can also result in cardiac overload (Raynaud A et al, 2010)
III. INDICATIONS (ACR–SIR PRACTICE GUIDELINE, 2013)
A. Indications for EMDA include, but are not limited to:
1. Stenoses without thrombosis occurring in a hemodialysis graft or
fistula if the stenosis is greater than 50% reduction in luminal diameter
and is considered functionally significant (see definitions above). The
percent stenosis reported can vary considerably depending on the
reference chosen, that is, the smaller graft or vein upstream (relative to
direction of blood flow) to the lesion versus a larger vein downstream
(relative to direction of blood flow). Percent stenosis may also be affected
by the presence or absence of blood flow in the access at the time of
measurement.
2. Stenosis associated with thrombosis. Thrombosis is associated with
underlying venous stenosis in greater than 85% of cases.
3. Central vein stenosis greater than 50% lumen reduction, when the
vascular access is haemo-dynamically compromised, and clinical
parameters such as arm swelling or frequently failing access are present.
Endovascular intervention with transluminal angioplasty is the preferred
treatment of central vein stenosis (Clinical practice guidelines for vascular access,
2007).
4. Autogenous fistulae that have failed to mature after 4 to 6 weeks.
Treatments include:
a. Balloon angioplasty of the inflow artery, arterio-venous
anastomosis, Juxta-anastomotic segment or outflow segments to increase
blood flow to the native vein. Multiple areas of stenoses may exist in non-
maturing fistulae
b. Interruption of venous tributaries that divert blood flow from
the primary venous segment improves blood flow and thereby promotes
maturation of the fistula
B. Indications for Endo-luminal Stent Placement
Several studies have demonstrated acceptable patencies for stent
deployment following balloon angioplasty failure, especially for central
vein lesions. However, several prospective randomized trials have failed
to show a benefit of bare stents over percutaneous transluminal
angioplasty (PTA) alone in the treatment of peri-anastomotic stenoses.
Current indications for endo-luminal stent placement include:
1. Persistence of a significant venous stenosis that has failed
balloon angioplasty and surgical access is difficult, surgery is
contraindicated, or there are limited remaining access sites.
2. A significant central vein stenosis that has either failed balloon
angioplasty or recurred within a 3 month period following an initially
successful balloon angioplasty (Clinical practice guidelines for vascular access,
2007).
3. Rupture of an outflow vein following balloon angioplasty that
cannot be controlled with balloon tamponade.
The threshold for these indications is 95%. When fewer than 95%
of procedures are for these indications, the department will review the
process of patient selection.
Stent grafts may provide longer patency than bare stents for the
venous anastomosis of grafts. A recent prospective randomized
multicenter study showed better primary target lesion and circuit
patencies after stent graft placement at the venous anastomosis of grafts
than after angioplasty alone). Stent grafts have also been used to treat
intra-access pseudo-aneurysms in case reports and small series. More
studies are needed before the role of covered stents for prosthetic graft
venous anastomoses and other applications including pseudo-aneurysms,
autogenous fistulas, and central veins can be determined. (Haskal ZJ et al,
2010)
C. Indications for Treatment of Steal
Steal can manifest by cardiac failure or ischemic symptoms,
including paresthesias, pain, motor weakness, sensory loss, or tissue loss.
When ischemic symptoms occur in the presence of an atherosclerotic
stenosis in the native arterial supply to the extremity, arterial angioplasty
can relieve the symptoms When there is no arterial lesion, decreasing the
flow in the graft or fistula by placing a flow restricting band across the
access near the arterial anastomosis can also improve or relieve
symptoms of steal. Due to access thrombosis complications after surgical
banding , a modified banding technique using an inflated angioplasty
balloon to accurately size the residual lumen has been used. A more
complicated surgical procedure known as distal revascularization with
interval ligation (DRIL) can also relieve symptoms. (Raynaud A et al, 2010).
IV. CONTRAINDICATIONS (ACR–SIR PRACTICE GUIDELINE,
2013)
The decision to treat a hemodialysis access with endovascular
techniques is always made in light of the patient’s clinical condition, the
number of alternative access sites available, and the expertise of the
treating physician.
A. Absolute Contraindication
Active infection of the vascular access.
B. Relative Contraindications
1. Severe contrast allergy.
2. Severe hyperkalemia, acidosis, or other life-threatening
abnormality of blood chemistry that requires immediate dialysis.
3 Known right to left shunt.
4. Severe cardiopulmonary disease.
IV. TECHNIQUE
Fistulography
The most common cause of AV graft or fistula failure resides in
stenosis at the venous anastomosis or in the venous outflow tract. An
approach to diagnostic fistulography, therefore, begins with cannulation
of the venous limb of the graft or the dilated venous outflow of the fistula
using the Seldinger over-the-wire technique with a simple 18-gauge
angio-cath. Digital subtraction techniques permit the acquisition of
abundant information with small hand injections of contrast agents.
Several injections utilizing multiple projections are usually required to
adequately visualize the venous anastomosis and often complex collateral
network of venous outflow channels. It is imperative to visualize the
entire venous outflow, including the central venous system, to exclude the
presence of occult occlusive disease. There is a significant incidence of
subclavian vein stenosis in patients who have previously undergone
placement of subclavian dialysis catheters. Only visualization of the
central venous system can exclude pathology at this site as the cause for
access dysfunction. A qualitative appraisal of fistula flow is made during
contrast injection. Flow through a patent, obstruction-free access site
should be rapid and should not demonstrate any areas of stagnation (miller
G. et al 2010).
By manipulating the diagnostic catheter under fluoroscopy toward
the arterial limb of the graft or the AV anastomosis of the fistula, of the
arterial inflow can be accomplished. A tourniquet or blood pressure cuff
inflated above the elbow to a pressure exceeding systemic blood pressure
will interrupt flow and allow contrast to reflux into the arterial limb of the
graft, enabling visualization of the arterial anastomosis and arterial
inflow. If needed, a guide wire followed by a diagnostic catheter can be
advanced retrograde up the brachial artery to the takeoff of the subclavian
artery to completely assess the arterial tree and exclude obstructive
lesions of the arterial inflow as a cause of access dysfunction. (Roach et al,
2011).
As an alternative, diagnostic fistulography can be performed
through indwelling dialysis needles following a dialysis treatment. The
needles are capped and secured by the dialysis staff after the run is
completed and the patient is transported to the imaging suite. The
indwelling dialysis needles provide a conduit for contrast injection
without the need for additional cannulation of the access. (Roach et al,
2011).
If therapeutic intervention such as balloon angioplasty is
subsequently indicated, guide wires may be introduced and the needles
exchanged for appropriately sized sheaths.
Intervention
Balloon angioplasty is readily accomplished at the time of
diagnostic fistulography. An appropriately sized sheath is advanced over
a guide wire into either the venous or arterial limb of the fistula or graft.
Sheath size will be guided by the selection of balloon catheters and
should always begin with the smallest diameter possible to accomplish
the intervention. Generally, simple balloon angioplasty can be performed
through a 6F sheath; however, sheaths ranging in size from 5 F to 11F
should be at hand. An appropriate selection of guide wires is necessary
and should be available in a range of sizes (0.025 to 0.038 in.) and
variable qualities (stiff, steerable, hydrophilic). Similarly, angioplasty
catheters—which come in a number of different balloon diameters,
balloon lengths, shaft size and balloon materials—should be readily
accessible. (Roach et al, 2011).
A guide wire is advanced through the sheath and across the
stenotic lesion. Once guide wire access is obtained, the balloon
angioplasty catheter can be advanced across the lesion as well. Balloon
inflation is performed using a dilute solution of contrast and a syringe
with pressure monitoring capabilities. (Roach et al, 2011).
Most patients require conventional angioplasty balloons for
stenosis at or adjacent to arteriovenous anastomosis, ultra-high pressure
balloons capable of exceeding pressures more than 20 atm are required
for lesions in the draining vein for full effacement of the waist of the
balloon. Cutting balloons are used for lesions resistant to ultra-high
pressure balloons. (Trerotola SO et al, 2011).
For venous anastomotic lesions 8-9 mm balloons are required, for
stenosis in the vein periphery balloons of 9-12 mm is required and for
arterial or anastomotic arterial lesions 5-6 mm balloons are required.
(Friedman A. et al 2010).
At the conclusion of the angioplasty procedure, completion
fistulography should confirm a widely patent access with brisk flow
throughout if the intervention was successful. Any residual focal
pressure gradient should prompt repeat angioplasty with upsizing of the
balloon by 1 mm.
Tran-radial arterial puncture technique:
The radial artery is retrograde punctured with a 30 mm 20-G
sheathed needle (Terumo, Tokyo, Japan) and then slowly withdrawn to
allow for blood purge from the central hub of the needle. After the needle
is removed, a 45-cm, 0.025-in hydrophilic guide wire is inserted through
the bleeding hub. The 20-G soft sheath is removed and a 6-Fr short sheath
(7 cm; Terumo, Tokyo, Japan) is introduced into the radial artery through
the guide wire, near but distal to the radial-cephalic anastomotic site. The
guide wire is then removed, leaving the sheath in place, and normal saline
is flushed into the sheath. The 6-Fr short sheath is then fixed in place.
Heparin (5000 IU per intravenous bolus) is routinely given after the
sheath was inserted. The contraindications to the trans-radial approach is
any of the following: (1) radial artery not palpable, (2) abnormal Allen’s
test, (3) radial-cephalic anastomosis located <2 cm proximal to the radial
styloid process. (Wu CC et al, 2011).
TECHNIQUES FOR MATURATION (Miller G. et al 2010)
A complex series of techniques are used to successfully mature
AVFs. First, detailed ultrasonography of the AVF is performed to
determine the vein size (1–3 mm, 3–6 mm, > 6 mm), fistula vein depth
(greater or less than 6 mm), location of competing branch veins (if any),
and the best site for micro-puncture needle cannulation. Small veins
require an initial sheath less approach and use of 0.018-inch wires and
balloon catheters to prevent occlusion of the lumen by a sheath.
Frequently, the best site for initial cannulation is under ultrasound
guidance into the distal radial artery or in an outflow vein where the
lumen is larger. Bidirectional wires should always be present to stabilize
both inflow and outflow venous and arterial pathways before the initial
angioplasty. Heparin is generally not necessary, but if long segments of
vein (> 10 cm) require angioplasty, 3,000 units of heparin should be
administered.
Ultrasound will also help determine if the fistula has a primary
outflow vein. Frequently, numerous outflow choices exist, and the
primary outflow should be chosen with the strongest consideration given
to whether it has a straight-line pathway that connects into the brachial
and basilic veins. Angioplasty of this selected vein, no matter how
initially small in diameter, should occur in 1-mm increments up to 6 mm
at the first visit. Residual collateral vessels that continue to show
diversion of flow on angiography should then be eliminated. Bidirectional
access should be used to dilate all segments of the fistula with long-length
balloons from the arterial anastomosis to the outflow veins. Significant
venous spasm after angioplasty indicates that a larger balloon is needed to
fracture the circumferential muscle fibers that are contracting in response
to an undersized balloon.
o Flow rerouting is a deliberate process of diverting blood flow into
veins that are known to have straight line flow to the central
circulation. Under road map guidance, a guide wire is used to
traverse the intended fistula vein. Then, balloon angioplasty
follows the guide wire, and a pathway of least resistance is created.
o Staged balloon angioplasty maturation with long-length balloons
(80–100 mm) entails sequentially dilating the entire length of the
fistula body to increase the fistula target size for cannulation.
Dilatation of the fistula is performed with an angioplasty balloon to
treat any focal stenoses or to simply upsize the entire length of the
fistula. Any residual stenoses are then fully effaced using ultra-
high-pressure balloons at up to 36 atm.
o Limited controlled extravasation is an arterial inflow control
technique and systematic process of angioplasty across the
proximal vein (toward central and outflow) followed by the distal
vein (toward periphery and arterial anastomosis) to avoid inflow
pressure from exerting pressure forces on angioplasty-weakened
tissues. This technique utilizes either an inflow occlusion balloon
or manual pressure on the arterial anastomosis. Inflow control must
be maintained during all phases of balloon inflation/deflation to
avoid intrafistula pressure spikes with subsequent back-pressure
injuries, complicating angioplasty across long segments of vein.
o Competing branch vein elimination involves coil embolization or
surgical ligation of competing branch veins. Veins should only be
considered to be significant only if they are 3 to 8 mm in diameter
and have a persistent high-velocity imaged flow or a palpable thrill
after angioplasty of the main fistula channel. Coil embolization is
the method of choice for veins deeper than 3 mm. surgical ligation
of competing branch veins is used to eliminate superficial veins (<
3 mm deep).
o Vessel thickening angioplasty refers to a method of angioplasty we
use to help elderly patients with exceedingly thin skin avoid severe
infiltrations upon needle cannulation. Angioplasty of a 6-mm-
diameter vein with a 7-mm-diameter balloon will result in fracture
of the wall and inflammation of the vein. Three weeks after
angioplasty, the vein dilates and the wall thickens. Inflammation of
the vein wall also facilitates incorporation of the skin with the vein
wall, which is essential in preventing infiltrations.
Usually, a fistula < 6 mm deep is ready for use after the first
maturation treatment. Deeper fistulas must have a larger circumference in
order to be cannulated and therefore require more maturation procedures.
Continue to angioplasty the AVF in this manner every 2 to 3 weeks until
it becomes suitable for dialysis and easy to cannulate. This 2- to 3-week
interval between angioplasty procedures is necessary to allow for healing
of the vessel wall.
V. COMPLICATIONS
With a clinically significant morbidity rate of less than five
percent, PTA can be considered a safe procedure. The most common
complications are vein rupture at the angioplasty site, acute access
thrombosis and pseudoaneurysm formation. If possible, self-expanding
stents are used to treat vein ruptures, otherwise surgical intervention is
needed. Other reported complications include puncture site bleeding,
bacteremia and allergic reactions to contrast medium.
VI. EVALUATION OF THE EFFECT OF PTA
K/DOQI recommends a residual stenosis of less than 30% after
PTA. However, several studies have shown that angiographic result of
PTA is poorly related to its subsequent patency. Furthermore, the
likelihood of access thrombosis is 80% if angioplasty fails to improve
access flow by at least 20%. Recently the SCVIR Technology
Assessment committee recommended that PTA success should be
expressed in both angiographic and functional parameters. A successful
PTA procedure should lead to an increase in access flow of 250-300
mL/min, The percentage of PTA procedures resulting in access flow less
than the threshold value of 600 mL/min was 34% in AVG and 50% in
AVF. Schwab et al defined failure of PTA as an increase in access flow
less than 20%, which occurred in 21% of grafts. This lack of effect in a
minority of patients may be caused by rapid recoil of stenotic lesion,
occurring in the period between PTA and the first access flow
measurement. Intravascular ultrasound after PTA showed that immediate
elastic recoil occurred in 50% of the stenotic lesions. Access flow
measurements, during or immediately after PTA, made in the intervention
room could be helpful to optimize procedure results. (Farquharson F. et al
2013).
VII. PATENCY RATES
Numerous reports have demonstrated that PTA effectively
improves access function. However, comparing patency rates is difficult
because of differences in patient selection, access types and definitions of
efficiency of the PTA procedure. Initial success rates of PTA i.e. post–
PTA rest stenosis less than 30%, range from 80 to 94. The highest rate of
technical failure is associated with central lesions. Primary patency rates
at six months after PTA range from 43 to 77%, again with poorest long
term success in central lesions (ranging from nearly 25% to 42% at 6
months).
Only one controlled surveillance study evaluated PTA results in
AVF With a six-month patency of more than 95% PTA seems to be more
successful in AVF than in AVG. Also, the mean time interval for re-PTA
is longer for AVF than AVG (169 vs. 109 days), indicating a slower
development of restenosis in AVF. Recently, Beathard et al reported on
the beneficial effect of PTA in AVF that failed to mature. Angioplasty
was performed to treat venous and arterial stenosis with a success rate of
nearly 100%. In the great majority of AVF, hemodialysis could be
initiated. Clark et al along with others, (KDOQI Clinical Practice Guidelines,
2007) linked non-maturation of AVFs to stenotic lesions within the access,
while Beathard et al has proposed that competing side branches unrelated
to stenosis account for inadequate maturation. Endovascular
interventional techniques proved to be successful in treating both
problems using percutaneous transluminal angioplasty to treat focal
stenoses and coil embolization and ligation to eliminate competing
branch veins Turmel-Rodrigues et al (2009) recently facilitated maturation
in 96% of patients with failing Brescia-Cimino fistulas who underwent
long-segment arterial angioplasty of the radial artery to 4 mm in diameter
to support the flow rates necessary to promote maturation. (Clark TW et al,
2007)
In a 2009 study published in the Journal of Vascular Access, 118
of 122 nonmaturing fistulas were salvaged by simultaneously dilating
both focal and long-segment arterial and venous stenoses and eliminating
collateral veins (Miller G. et al, 2010). An important aspect of this study was
the concept of relative fistula depth and its impact on maturation; fistula
diameter and depth are interdependent factors, and the appropriate
diameter for a fistula is relative to the depth of the target vein. Although
Nassar et al salvaged 83% of AVFs, in this study 97% of non-matured
AVFs were salvageable with a more aggressive approach to dilating
diffusely strictured veins, forced BAM of deep veins up to 16 mm in
diameter, and elimination of nearly all distal and mid-fistula collateral
veins. These otherwise abandoned AVFs were successfully matured and
supported hemodialysis in as little as 1 to 6 weeks after the initial
angioplasty.
Results of PTA after vascular access thrombosis are generally
worse, with a reported six-month patency rate of only 19% in one study
including AVG only. This finding suggests that the outcome of PTA of
less severe stenosis is superior to the outcome of PTA of more severe
stenosis that lead to thrombosis, emphasizing the importance of effective
surveillance of access stenosis and pre-emptive PTA. Primary patency
after surgical thrombectomy seems slightly better, but remains
disappointing. Dougherty et al (1999) stressed the fact that endovascular
treatment is more expensive because of frequent secondary surgery after
technical failure. However, it is important to keep in mind that surgical
thrombectomy is followed by reconstruction of the anastomosis in most
cases. As a consequence, after several surgical revisions a new
anastomosis often can no longer be created. Of course, the creation of a
new access also results in extra costs and morbidity. (Robert D. et al, 2013).
PTA results in substantial vascular injury, which may trigger
development of restenosis. However, several authors found similar
success rates after first, second or third PTA (Robert D. et al, 2013).
PATIENTS
AND
METHODS
Patients and methods
This study included 30 patients who presented to surgical unit in Fayoum
University Hospital (FUH) and Kasr Al-ainy Hospital with failed to
mature arterio-venous fistula in the period from April 2014 to January
2015. We performed thirty interventions for those thirty patients on
hemodialysis for chronic renal failure. The study included eighteen
women and twelve men with different age groups. All Patients who were
referred from the dialysis unit were subjected to diagnostic duplex
ultrasonography (DUS) and or diagnostic fistulogram.
1. Selection criteria
The aim of the study: was to evaluate the most possible causes behind
Arterio-venous fistula immaturity in ESRD patients with suitable AVF,
roles played by age, sex, DM and hypertension and evaluate the
endovascular management in this issue.
Inclusion criteria: the study included patients with :
Mal-functioning arterio-venous fistula during first 6-8 weeks of setup
presented with:
Fistula with weak thrill
Pulse with no thrill
Venous hypertension
Edema of the limb.
Insufficient flow during dialysis
Difficult cannulation.
Exclusion criteria: the patients excluded include:
Thrombosed arteriovenous fistula which means there is no even
pulse palpable by physical examination.
Physical evidence of arteriovenous fistula related infection.
Patient with history of major allergic reaction to IV radio contrast
agents.
Patients unwilling to undergo the procedure or missed with follow
up.
2. Pre-procedural evaluation
All patients were subjected for full history taking including personal
history (age and gender) , risk factors as hypertension and Diabetes
mellitus and clinical examination
A. Complaints as :
Insufficient flow on dialysis or inability to dialyze from the fistula.
Difficult multi trial cannulation in each dialysis session.
Swelling of the upper limb.
B. Physical examination:
Normally, the mature AVF has a soft pulse and the entire structure is
easily compressed. When the extremity is elevated the entire fistula will
generally collapse, at least partially.
1) Juxta-Anastomotic Venous Stenosis
This lesion can be easily diagnosed by palpation of the anastomosis and
distal vein. Normally, a very prominent thrill is present at the
anastomosis. In the absence of abnormalities, the pulse is soft and easily
compressible. With Juxta-anastomotic stenosis, a water-hammer pulse is
felt at the anastomosis. The thrill, which is normally continuous, is
present only in systole. As one move up the vein from the anastomosis
with the palpating finger, the pulse goes away rather abruptly as the site
of stenosis is encountered.
2) Accessory Veins
Frequently they are visible. If not, they can be detected by palpating the
fistula. Normally, the thrill that is palpable over the arterial anastomosis
disappears when the downstream (ante grade) fistula is manually
occluded (this causes flow to stop). If it does not disappear, an outflow
channel (accessory vein) is present below the point of occlusion.
Palpation of the fistula below the occlusion point will generally reveal the
location of the accessory vein by the presence of a thrill over its trunk. As
long as the main channel can be identified for occlusion, the entire length
of the vein can be evaluated by moving the point of fistula occlusion
progressively upwards.
3) Venous Stenosis
With downstream (ante grade) stenosis, the AVF becomes more forcibly
pulsatile and firm. It also enlarges rapidly, often taking on aneurysmal or
near-aneurysmal proportions. When the extremity is elevated, that portion
of the fistula distal to point of stenosis remains distended, while the
proximal portion collapses in the normal fashion. In addition, the pulse
diminishes abruptly as does the caliber of the vessel. Changes in the
location and character of thrills and bruits could be noted.
4) Central vein stenosis
In cases of severe stenosis, gross swelling of the access arm is frequently
seen. Catheter scar over the subclavian vein, both the disease and its
etiology become obvious. Multiple subcutaneous collaterals will
frequently be evident over the neck, upper chest and shoulder.
5) Difficult cannulation
Some patient complained of difficult cannulation in each session for
hemodialysis. DUS shows deep draining vein more than 10 mm.
3. Procedural technique
A. Endovascular intervention: A 6 French vascular introducer
sheath was inserted either percutaneous into the venous limb of the
AVF or in the radial artery .Open technique in the radial artery was
used as well. Diagnostic angiography was performed through the
sheath. A hydrophilic-coated, 0.035 inch terumo guide wire was
passed.
2000 units of heparin were administrated through the side port of the
introducer sheath into the AVF.A balloon catheter was then passed over
the guide wire and advanced to the lesion assisted by fluoroscopy.
According to the site 6-14 mm balloons were used. Balloon size was
determined based on the findings of fistulography. The balloon was then
inflated with a pressure inflation syringe until it opened fully (i.e. until
the waist of the stenosis impinged on the balloon). Inflation was sustained
for 30-60 seconds with a pressure of 12-14 atm applied. Multiple
inflations were used for resistant lesions. In case of central venous
stenosis, large caliber stents 10, 12 or 14 mm with variable lengths were
used successfully.
After PTA balloon and stenting, a set of arteriovenous fistulograms were
again performed to document the result of angioplasty.
Procedural assessment:
The result of PTA was considered technically successful if the degree of
residual stenosis was less than 30% as visualized using the fistulogram. A
clinically successful PTA procedure was defined as the ability to dialyze
3 consecutive times.
Primary patency was defined as patency during the interval between
primary intervention and repeated radiologic intervention because of
dysfunction. Secondary patency was defined as patency during the
interval between primary intervention and the time when the fistula was
surgically declotted, revised, or abandoned; the time when the patient
received a renal transplant; death or the time when the patient was lost to
follow up.
B. Ligation of accessory veins: Under local anesthesia, small skin
incision was done to ligate theses veins.
Procedural assessment:
The results were good. Follow up of these patients by DUS showed
increased flow and adequate dialysis session.
C. Superficialization of deep vein: Patients who complain of
difficult cannulation have undergone this procedure under local
anesthesia. All cases were female patients have brachiocephalic
shunt.
Procedural assessment:
Immediate improvement could be seen after that procedure which
was satisfactory for the patient and dialysis unit nurse.
4. Follow up
All patients were followed for 1week after the intervention with 3
successful sessions of dialysis. Complications and interventions were
recorded for this period. All patients showed primary patency for that
period.
RESULTS AND
DEMOGRAPHICS
Results and Demographics
This study included 30 patients presented with failed-to-mature arterio-venous fistula.
They had 9 open surgical and 21 peripheral endovascular interventions in the form of
percutaneous trans-luminal angioplasty.
Table (6) : Frequencies of demographic characters among studied
patients.
The age of patients ranged from 22 to 66 years old with high frequency of
66.6% are between 40-59 years old. The study included 12 (40%) males
and 18(60%) females. As regarding risk factors in our study; 36.6% of
patients have diabetes mellitus, (40%) have hypertension and 20%
patients have both.
Variables Number Percentage
Age groups
20-39 y 7 23.3 %
40-59 y 20 66.6 %
60-80 y 3 10 %
Sex
Male 12 40%
Female 18 60%
Risk factors
DM 11 36.6 %
HTN 12 40 %
Both 6 20 %
Fig6: Age groups and number of studied patients
Fig 7 frequency of Sex in studied group
40%
60%
Sex among study group
Male Female
23.3%
66.6%
10%
0%
10%
20%
30%
40%
50%
60%
70%
80%
20-39 yr 40-59 yr 60-80 yr
Age Groups among studied patients
Fig8: Risk factors among study groups
Table (7): Frequencies of Types of arterio-venous fistulae among
studied patients.
Our study included (40%) brachiocephalic AVFs, (36.6%) radio-cephalic
AVFs, (10%) brachio-basilic AVFs with Superficialization, (10%)
brachio-axillary PTFE bridge graft AVFs and (3.3%) brachio-axillary
saphenous graft AVF.
Types of AVF Number Percentage
Brachio-cephalic AVF 12 40 %
Radio-cephalic AVF 11 36.6 %
Brachio-basilic AVF 3 10 %
Brachio-axillary PTFE bridge graft Fistula 3 10 %
Brachio-axillary- saphenous graft Fistula 1 3.3 %
40% 36.6%
20%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
HTN DM Both
Risk Factors among study group
Fig9: Types of AVFs among study group
Table (8): Frequencies of Modes of Interventions among studied
patients.
Open surgery was performed in (30%) of patients 16.8% of them did
superficialization, and 6.6% did Disconnection of veins under LA, same
percentage for Proximalization of fistula. Endo-vascular surgery was
performed in (70%) of patients 43.3% of them did PTABS, and 26.7%
did PTAB.
Type Number Percentage
Open Surgery n= 9 (30 %)
Superficialization 5 16.8%
Disconnection of vienS under LA 2 6.6%
Proximalization of fistula 2 6.6%
40% 36.6%
10% 10%
3.3%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Brachio-cephalicAVF
Radio-cephalic AVF Brachio-basilic AVF PTFE bridge graft Saphenous bridgegraft
Types of AVF among study group
Endovascular Surgery n=21 (70 %)
PTABS 13 43.3%
PTAB 8 26.7%
Fig 10: Types of interventions among study group
Table (9): Frequencies of Endovascular access among studied
patients.
Trans-arterial approach was applied in 46.6% of cases where trans-
venous approach was applied in 20% of cases and trans- PTFE graft in
3.3% of case.
Type Number Percentage
Arterial 14 46.6 %
Venous 6 20 %
30%
70%
Modes of Intervention among study group
Open surgery Endovascular surgery
Bridge graft 1 3.3 %
Fig 11: Types of Endo-vascular access among study group.
Table (10): Frequencies of different causes of failed AVF Maturation
among studied patients.
We'd found that causes of failed maturation were 30% because of central
vein stenosis followed by 23.3% to Juxta-anastomotic venous stenosis
then 16.7% deep afferent vein, 13.3 % arterial occlusive disease 10%
proximal venous stenosis and , 6.7%for each accessory veins.
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Arterial Venous PTFE graft
46.6%
20%
3.3%
Tpes of Endovascular access among study group
Cause of failure Number Percentage
1 Central vein Stenosis 9 30%
2 Juxta-anastomotic venous stenosis 7 23.3%
3 Deep afferent vein 5 16.7%
4 Arterial occlusive disease 4 13.3%
5 Proximal venous stenosis 3 10%
6 Accessory veins 2 6.7%
Fig 12: causes of failed AVFs Maturation
Table (11): Frequencies of Failure of surgical intervention among
studied patients.
There were 86.6% of cases ultimate successful procedures with technical
and clinical success. All of which showed functional patency for 1 week.
Therewere2 cases of failed endo-vascular interventions which showed
recoil of innominate vein stenosis and multiple vein perforations for
30%
23.3%
16.7%
13.3%
10%
6.7%
0%
5%
10%
15%
20%
25%
30%
35%
Cause 1 Cause 2 Cause 3 Cause 4 Cause 5 Cause 6
Frequency of cases of AVF maturation failure
Juxta-anastomotic stenosis. There were2 cases of failed open surgery
which showed injured cephalic vein after Superficialization for deep
cephalic and injured cephalic vein for ligation of accessory veins.
Result Number Percentage
Success 26 86.6 %
Failure (n=4)
Surgical failure 2 6.6 %
Endovascular failure 2 6.6 %
Fig 13: Frequencies of Failure of surgical intervention among studied patients.
Table (12): Comparison of age among different causes of failure.
There is statistical significance difference with p-value <0.05 between different
causes of failure as regards to age with high mean of age among patient with central
vein stenosis followed by patients with Arterial occlusive disease.
86.6%
6.6%
6.6%
Incidence of Failed interventions
succeeded Interventions Failed Open surgery
Failed Endo-vascular Surgery
Cause of failure Age (years) p-
value No. Mean SD
1 Juxta-anastomotic venous
stenosis 7 43 11.2
0.04*
2 Proximal venous stenosis 3 39.3 6
3 Central vein Stenosis 9 53.7 9.2
4 Deep afferent vein 5 44.8 8.5
5 Accessory veins 2 31 12.7
6 Arterial occlusive disease 4 48.5 6.7
Fig. 14: Mean age among different failure causes
Table (13): Comparison of different causes of failure among different
gender.
0
10
20
30
40
50
60
Central veinStenosis
Arterial occlusivedisease
Deep afferentvein
Juxta-anastomoticvenous stenosis
Proximal venousstenosis
Accessory veins
53.7
48.5 44.8
43 39.3
31
Mean age among different failure causes
There is no statistical significance difference with p-value >0.05 between
different gender as regards to causes of failure.
Cause of failure
Male (n=12)
Female (n=18) p-
value No. % No. %
1 Juxta-anastomotic venous
stenosis 3 25% 4 22.2%
0.1
2 Proximal venous stenosis 1 8.3% 2 11.1%
3 Central vein Stenosis 3 25% 6 33.3%
4 Deep afferent vein 0 0% 5 27.8%
5 Accessory veins 2 16.7% 0 0%
6 Arterial occlusive disease 3 25% 1 5.6%
Table (14): Comparison of different causes of failure among diabetic
groups.
There is statistical significance difference with p-value <0.05 between
different diabetic groups as regards to causes of failure with high
percentage of Deep afferent vein cause of failure among diabetic group,
and Central vein stenosis cause of failure among non-diabetic group.
Cause of failure
DM (n=11) Not- DM
(n=19) p-
value No. % No. %
1 Juxta-anastomotic venous
stenosis 1 9.1% 6 31.6%
0.006*
2 Proximal venous stenosis 1 9.1% 2 10.5%
3 Central vein Stenosis 1 9.1% 8 42.1%
4 Deep afferent vein 5 45.5% 0 0%
5 Accessory veins 0 0% 2 10.5%
6 Arterial occlusive disease 3 27.3% 1 5.3%
Fig 15: Different causes of failure among diabetic groups
Table (15): Comparison of different causes of failure among
hypertension groups.
There is no statistical significance difference with p-value >0.05 between
different hypertension groups as regards to causes of failure.
Cause of failure
Hypertensive (n=12)
Not-
hypertensive (n=18)
p-
value No. % No. %
1 Juxta-anastomotic venous
stenosis 3 25% 4 22.2%
0.1
2 Proximal venous stenosis 1 8.3% 2 11.1%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Juxta-anastomoticvenous stenosis
Proximal venousstenosis
Central veinStenosis
Deep afferent vein Accessory veins Arterial occlusivedisease
9.1% 9.1% 9.1%
45.5%
0%
27.3% 31.6%
10.5%
42.1%
0%
10.5%
5.3%
DM Not-DM
3 Central vein Stenosis 2 16.7% 7 38.9%
4 Deep afferent vein 1 8.3% 4 22.2%
5 Accessory veins 1 8.3% 1 5.6%
6 Arterial occlusive disease 4 33.3% 0 0%
Table (16): Comparison of different causes of failure among types of
AVF.
There is no statistical significance difference with p-value >0.05 between
different types of AVF as regards to causes of failure.
Cause of failure Natural
AVF
Synthetic
AVF
p-
value
1 Juxta-anastomotic venous stenosis 7(26.9%) 0
0.2
2 Proximal venous stenosis 2(7.7%) 1(25%)
3 Central vein Stenosis 8(30.8%) 1(25%)
4 Deep afferent vein 5(19.2%) 0
5 Accessory veins 2(7.7%) 0
6 Arterial occlusive disease 2(7.7%) 2(50%)
Table (17): Comparison of different causes of failure among results
of intervention.
There is no statistical significance difference with p-value >0.05 between
different results of intervention as regards to causes of failure.
Cause of failure
Success (n=26)
Failed (n=4) p-
value No. % No. %
1 Juxta-anastomotic venous
stenosis 6 23.1% 1 25% 0.6
2 Proximal venous stenosis 3 11.5% 0 0%
3 Central vein Stenosis 8 30.8% 1 25%
4 Deep afferent vein 4 15.4% 1 25%
5 Accessory veins 1 3.8% 1 25%
6 Arterial occlusive disease 4 15.4% 0 0%
Table (18): Comparison of different causes of failure among results
of intervention.
There is no statistical significance difference with p-value >0.05 between
different results of intervention as regards to types of intervention.
Intervention types
Success (n=26)
Failed (n=4) p-
value No. % No. %
1 Open Surgery 7 26.9% 2 50%
0.3 2
Endovascular
Surgery 19 73.1% 2 50%
Statistical Analysis
Data was collected and coded to facilitate data manipulation and
double entered into Microsoft Access and data analysis was
performed using SPSS software version 18 under windows 7.
Simple descriptive analysis in the form of numbers and percentages
for qualitative data, and arithmetic means as central tendency
measurement, standard deviations as measure of dispersion for
quantitative parametric data, and inferential statistic test:
- For quantitative parametric data :
One way ANOVA test in comparing more than two
independent groups of quantitative data.
For qualitative data
Chi square test to compare two of more than two
qualitative groups.
The level P ≤ 0.05 was considered the cut-off value for
significance.
DISCUSSION
Discussion
Vascular access complications are one of the main causes
associated with an increase in morbidity and mortality in stage 5 chronic
kidney disease patients. To improve QOL and overall outcomes for HD
patients, 2 primary goals were originally put forth in the vascular access
guidelines to emphasis placement of a functioning fistula.
• Increase the placement of native fistulae
• Detect access dysfunction before access thrombosis.
(DOQI CPGs for VA 2007)
The AVF is regarded as the vascular access of choice for he-
modialysis because of its superior patency and lower complication rates.
Central venous stenosis is considered the major cause of AVFs failed
maturation. The pathogenesis of venous stenosis is not fully understood.
The pathophysiology underlying the occurrence of stenosis is complex. It
includes cellular proliferation, microvessel formation leading finally to
venous intimal hyperplasia. The National Kidney Foundation/Kidney
Disease Outcomes Quality Initiative Task Force has suggested PTA as a
preferred treatment for vascular access stenosis ≥ 50% with clinical or
physiologic abnormalities. (David C. et al. 2013)
In our study, we had found that central venous stenosis
representing 30% of cases (9/30), followed by Juxta-anastomotic stenosis
being 23.3%. More than 16% of cases showed deep afferent veins,
followed by arterial causes and proximal vein stenosis with percentage of
4 and 3 % respectively.
In our study, Brachio-cephalic and radio-cephalic VA represented
60% and 36% of failed to mature vascular access respectively.
As the understanding necessary to promote maturation of fistulas
has evolved, the old ―watch-and-wait‖ approach to fistula maturation has
been replaced by early endovascular interventions over abandonment and
surgical revision. KDOQI guidelines support evaluating fistulas for
failure to mature if they are not usable at 6 to 8 weeks. More recently,
accelerated maturation techniques including forced balloon angioplasty
maturation (BAM) of both arterial and venous segments as long as 20 to
30 cm in length have been promoted to rapidly facilitate AVF usage in as
little as 2 to 6 weeks after the initial 6 to 8 week waiting period. (William
D. et al 2013)
Results of PTA after vascular access thrombosis are generally
worse, with a reported six-month patency rate of only 19% in one study
including AVG only. This finding suggests that the outcome of PTA of
less severe stenosis is superior to the outcome of PTA of more severe
stenosis that lead to thrombosis, emphasizing the importance of effective
surveillance of access stenosis and pre-emptive PTA. (Bart L. et al.
2012)
In our study all patients exhibited insufficient flow on
hemodialysis which is a strong predictor of imminent thrombosis which is
associated with higher risk of subsequent failure of the vascular access.
Ten patients underwent fistulography. All patients exhibited baseline
stenosis ≥50% with clinical abnormalities. Of the twenty one cases
subjected to angioplasty, nineteen cases showed 1 week patency rate,
which may be explained by intervention prior to thrombosis with more
favorable outcome.
In most studies, post-PTA stenosis is used to express the
efficiency of PTA procedures. However, post-PTA stenosis poorly
predicts patency rates after PTA (Chinenye O.et al 2014).
The society for cardiovascular interventional radiology (SCVIR)
Technology Assessment Committee recommended reporting both
angiographic and functional data as efficacy parameters for PTA. A
successful PTA procedure should lead to an increase in access flow of
250-300 mL/min (Farquharson F. et al 2013).
(Oleg L. et al. 2014) defined failure of PTA as an increase in
access flow less than 20%, which occurred in 21% of grafts. This lack of
effect in a minority of patients may be caused by rapid recoil of stenotic
lesion, occurring in the period between PTA and the first access flow
measurement. Intravascular ultrasound after PTA showed that immediate
elastic recoil occurred in 50% of the stenotic lesions Access flow
measurements, during or immediately after PTA, made in the intervention
room, could be helpful to optimize procedure results. (Anil K. et al, 2014).
The highest rate of technical failure is associated with central
lesions. Primary patency rates at six months after PTA range from 43 to
77%, again with poorest long term success in central lesions. (Ayumi S. et
al. 2013).
In our study success was expressed in both technical and
functional success. Technical success was achieved in 86.6 %of cases in
the form of residual stenosis less than 30% after PTA. Functional success
which means ability to dialyze three consecutive times was achieved in
all cases with good flow on hemodialysis with primary patency of one
week.
A more recent study evaluated PTA results in AVF. PTA seems to
be more successful in AVF than in AVG. Also, the mean time interval for
re-PTA is longer for AVF than AVG, indicating a slower development of
restenosis in AVF (Allon M. et al, 2013)
(H. Han et al 2013) Technical and clinical success rates were
95.7% in AVFs and 86.5% in AVGs, respectively. The primary and
secondary patency rates were 71.9% and 82.8% at 1 year, 60.1% and
82.0% at 2 years, and 54.5% and 82.0% at 3 years, respectively. All
immature AVFs had significant anatomical causes of failure to mature,
which could be safely and effectively salvaged with endovascular
treatment. A degree of stenosis >90% was an independent predictor for
both the primary and secondary patency after the treatment.
In our study, This remarkable primary patency (nineteen cases out
of twenty (70%) subjected to PTA showed primary patency for 1week
may be explained by early referral of cases prior to thrombosis, all cases
with central lesions subjected to PTA which is associated with fair
outcome and finally the study didn't only include cases with AVF but also
with AVG of synthetic and native material.
PTA results in substantial vascular injury, which may trigger
development of restenosis. However, several authors found similar
success rates after first, second or third PTA (Bernardo F. et al. 2011).
In our study none of the subjects was subjected to re-PTA, so
results after re-PTA could not be evaluated. However substantial vascular
injury may have occurred in the form of clinically insignificant stenosis.
The trans-arterial approach was used in the majority of cases
(46%, 14/30) either percutaneous or open and proved to overcome the
trans-venous approach regarding sheath position being sufficient to treat
all lesions and post puncture compression without the flow within the
fistula being compromised.
PTA can be considered a safe procedure. The most common
complications are vein rupture at the angioplasty site, acute access
thrombosis and pseudoaneurysm formation. If possible, self-expanding
stents are used to treat vein ruptures, otherwise surgical intervention is
needed. Other reported complications include puncture site bleeding,
bacteremia and allergic reactions to contrast medium (Brenda L. et al.
2011)
In our study complications occurred in only 4 patients in the form
of hematoma and post puncture site bleeding and the procedure was
aborted.
The current study was conducted in a relatively small number of
patients. Therefore, further randomized, large-scale studies are required.
In our study, open surgical intervention was done for nine patients
(30%). Two patients were subjected for failure due to injured cephalic
vein during superficialization and another one for injured cephalic vein
for ligation of accessory veins.
Overall AVF functional maturation rate in one study was 53.7%
(52/97). Female gender showed significant association with non-
maturation (P = 0.004). . (Khalid B. et al. 2014)
In our study, Female patients were 60% (18/30) of failed to mature
VA patients but there is no statistical significance difference with p-value
>0.05 between different gender as regards to causes of failure
Age older than 85 years showed 60% of failed to mature VA.
Limitation was lack of access creation history before dialysis therapy
initiation. He concluded that even patients judged at highest risk can have
successful AVF construction and initiate dialysis therapy through a
functioning AVF. (Michael P et al. 2012)
In our study, age group (40-59) years old represented 66% (20\30)
of the failed to mature VA. Age range from 20 to 39 and 60 to80 being
23% and 10% respectively. There is statistical significance difference
with p-value <0.05 between different causes of failure as regards to age
with high mean of age among patient with central vein stenosis(Mean
53.7, SD 9.2) followed by patients with Arterial occlusive disease(Mean
48.5,SD 6.7)
AVF non-maturation was not associated with patient age or
diabetes, although both variables were associated significantly with
severe medial fibrosis. Conversely, AVF non-maturation was higher in
women than men despite similar medial fibrosis in both sexes (Michael
A. et al. 2011).
In our study, 36.6 %( 11/30) of patients has DM was associated
with failed to mature VA and 20% (6/30) had both DM and
Hypertension. 6.6% of total patients failed to have mature VA were
medically free.
There is statistical significance difference with p-value <0.05
between different diabetic groups as regards to causes of failure with high
percentage of Deep afferent vein(45.4%) cause of failure among diabetic
group, and Central vein stenosis(42.1%) cause of failure among non-
diabetic group.
There is no statistical significance difference with p-value >0.05
between different hypertension groups as regards to causes of failure
In conclusion, PTA is an effective therapy in securing the
maturation of AVFs. Compared to surgery, PTA has several advantages,
including the fact that it is relatively simple, less invasive, shorter
procedure, causes less stress to the patient, enables immediate dialysis
without the need for central venous catheter, reduces the risk of infection,
and saves the patient’s veins. However, the open surgical and
endovascular treatment should be viewed as alternative or complementary
approaches rather than competitive ones (NKF-K/DOQI Clinical practice
guidelines for vascular access, 2007).
In our study, PTA Ballooning ±stenting was used
successfully in 70% of cases. Being relatively easy, done under local
anesthesia and could be done as outpatient procedure. Female patients
were associated with high incidence of failure to mature fistula. Age
group range from 40 to 59 years has more than 66% incidence of failure.
Brachio-cephalic AVFs and Radio-cephalic AVFs represent 40% and
36% of the failed to mature AVFs.
In our study, 23% of patients with failed to mature VA
complained of weak thrill and the same percentage for pulse with no
thrill, followed by swelling of the upper limb and difficult cannulation.
We had used duplex ultrasound in 66% of cases and
fistulogram for other cases.
SUMMARY
Summary
Chronic kidney disease is a major public health problem.
Vascular access to facilitate hemodialysis is provided by one of the
following three options: native arterio-venous fistula, prosthetic arterio-
venous grafts and central venous catheters.
Native arterio-venous fistula are the preferred mode of vascular
access worldwide due to its ability to provide high blood flow rates with
superior patency and low rate of complications.
Vascular access failure is a major source of morbidity,
mortality and expense for patients undergoing hemodialysis. Several
techniques have been described to maintain a hemodialysis access site;
varying from open surgical ones to percutaneous endovascular
approaches and sometimes a hybrid combination.
We have studied the causes of failed AVFs maturation and the
roles played by age, sex, DM, hypertension and evaluate the role of
endovascular interventions in assisted maturation.
Our study has included thirty patients fulfilling our eligibility
criteria with immature fistulae between April 2014 and January 2015 who
were followed up during the period of maturation (6-8 weeks) and for the
first 3 sessions.
Our study included thirty cases with age ranges from 22-65
years with 66.6% in the age 40-59 group. Female patients represented
60% of failed to mature fistula. 36.6% of patients had DM and 40% had
hypertension and 20% had DM and Hypertension.
Central venous stenosis was the most common cause of failure
to mature with a percentage of 30% (9/30). Juxta-anastomotic venous
stenosis came next with percentage of 23.3%. Deep afferent veins that
needed superficialization were 16.6% of cases. Brachio-cephalic shunt
made 40% of AVFs failed to mature and 36.6% for radio-cephalic shunts.
The most common presentations were weak thrill and pulse with no thrill
(23%) each followed by swelling of the upper limb (20%). Open surgery
was done for 30% and EVM was done for the rest.
We have used diagnostic ultrsound in 66% of total cases
managed. Fistulogram has been used for the remaining percentage of
cases.
Endovascular management has treated 70% of cases. Open
surgery was used for the remaining percentage.
The native arterio-venous fistula (AVF) is recommended as the
first choice due to its superior patency and lower complication rates over
grafts and catheters. Although arterio-venous fistula is the best available
form of hemodialysis access, yet a significant number of fistulas never
mature to support dialysis (early failure). EMDA can save many AVFs.
Female patients are associated with high incidence of failure to mature.
Also diabetic patient has more chance to fail to mature. Central venous
stenosis is the leading cause of failure to mature AVFs. Brachio-cephalic
AVFs and radio-cephalic AVFs had the highest chance of failure to
mature. DUS is invaluable tool in ESRD patient eligible for vascular
access placement regarding monitoring and early salvage prior to
thrombosis.
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Arabic
Summary
اىيخص باىيغة اىعشبة
الملخـص العـربـي
:مقذمة
عببا ببز اىنيبب اىببش شحيببة ىاببة اىنبب اىعبب اىضببة اىنيبب غسببو أصبب
اىتنبببشس اىصبببه تتببب اىتببب اىخاسجبببة ىيتحيبببة سبببنش ش متببب ابتنببباس بعبببذ 0691
.اىذة اىذسة اى
اال سببببب اىذبببببة االعبببببة اىببببب اىصبببببه اجبببببضة ىطبببببش اى حببببب اىتطبببببس
.عقد ذاس عي مي غسو عي باىحفاظ ىيشض
ىيبببذسة تنبببشس صبببه ببب ش ا اىثببباى اىذبببة االعبببة اىببب اىصبببه ىظبببا غببب
اخفببببا طيببببة ىفتببببشا اسبببب ميبببب غسببببو ىتحقبببب ما ببببة تببببذ عببببذال اىذببببة
. اىضاعفا عذال
اىصبببه طبببش صببباة باشبببا اىشت طبببة اىتنببباى اىبببش شبببذة بببا رىبببل ببب
ظببا تحقبب عبب بعببذا ببذ عيبب ؤشببش بب اىنيبب اىغسببو شضبب بب اىذببة ى عببة
.اىثاى اىذة ى عة اىصه
ىشضبببب اىستشببببف ىببببذ ه شببببعا االمثببببش اىسبببب بببب اىنيبببب ىيغسببببو اىصببببه شببببو
.اىتظة يضةاىذ
اجبببباى بببب% 01 حبببب تشببببنو اىصبببباة اىذببببة االعببببة اىبببب اىصببببه اشببببا
.اىتحذة اىالا اىني اىغسو ىشض اىصحة اىشعاة عي االفا
اىن بببش اىببب تجبببة اىذبببة االعبببة اىببب اىصبببه ىعبببذ االجتببباع االثبببش صاد ىقبببذ
اىعقببببذ ببببذ عيبببب اىنيبببب اىببببش شحيببببة اببببة بببب عببببا ىببببزا اىشضبببب عببببذد بببب
.اىاض
اىصبببحة اىشعابببة بشبببا ببب اىشضببب عبببذد تضببباع 1110 0660 عبببا بببب
ببب 311111 ببب امثبببش اىببب 111111 ببب اىنيببب ىيبببش اىائبببة اىشحيبببة ىشضببب
.ششع اىحاد اىقش م ش بشنو اىشق زا ضذ ا اىتق
االعبببت ه عبببذال ببب م بببش بشبببنو تقيبببو أ شببباا ببب تنىجبببة طفبببشة ظبببش ال
بببزا ضببب ببب , اال ببب ببب ىتنببب اىذبببة االعبببة اىببب باىصبببه اىشت طبببة اىتنببباى
عبببباش ىتحذببببذ اسصببببا ىضبببب ببببؤ شا اىجببببد تشمببببض تبببب, االعت بببباس بببب االدساك
.اىذة ى عة صه ضوأ طشقة اجو اىشض ا تاس
الهذف من العمل:
تببذه ببز اىذساسببة اىبب تقبب امثببش االسبب اء اىحتيببة سا عببذ ضبب اىصببية اىشببشاة
اىسذبببة ببب اىشضببب اىبببز عبببا اىبببذا اىنيببب بشاحيببب اال بببشة ببب جبببد صبببية
ببببة ىببببؤال اسبببب ة سبببب قا. ضبببب اىحيببببه اىنببببة بببب شببببنو تببببذ ببببادا تج
اىشض.
المرضى واآلليات:
معايير اخيار المرضى:
جيسببببا 2أسبببباب ت حتبببب اه 8اىبببب 9ببببت تابعببببة اىشضبببب بببب ه تببببشة اىضبببب بببب
ىيغسو اىني.
تببب تعشببب عببباش اىضببب مببباالتس جبببد استجببباه سبببية اىصبببه ببب مبببو جيسبببة غسبببو
و ىنو دققة 911 ع طش اىحق عذه تذ امتش ا سا
ببب تحقبب اىعبباش اىضمبببسة سببابقا اىبببس اىتقبب اىسبببشش تعببش اىشضبب اىبببز شببيا
اىجبببا ببب اىصبببتة اىضدجبببة ىت ببب ا ببب اسببب اء شبببو اىضببب ثبببوس قطبببش اىسبببذ
اىشببباسك ببب اىصبببية , ا يبببو ببب االسدة اىشمضبببة, بعبببذ اىسبببا ة بببب اىسبببذ اىجيبببذ
اىششا اىشاسك اىفاغشة.
سىمعايير استبعاد المرض
بببت اسبببت عاد اىشضببب اىيبببز جببب اىضببب ىبببذ اىشضببب اىشا ضببب ىيشببباسمة ببب بببز
اىذساسة.
سمعايير التقييم
اىفحص اىسشش.
االشعة اىجا اىصتة اىضدجة.
سببت اد بباه اىتبببائ اىبب بشببا امسبببو ىيتحيببو ببا خبببتص باىسبب اىجبب االبببشا
اىصاح ة.
ملخص:
إ جبببد بببذ و عبببرائ ضبببرشس ىتحقببب اى قبببرا اىطربببرو اىعبببرة اىثاىبببرة بببر
اىحببببراة ىشضببببر اىفشببببرو اىنيببببر اىببببض. اىخببببراسا اىثراىببببرة اىحراىببببرة تتضبببببر,
اىصببببببر اىشرشاببببببرة اىسرذببببببرة اىصببببببر اىصراعببببببرة اىقسراطببببببرش اىسرذببببببرة
شنببببرو اىفضببببرو ببببر اىصريببببرة اىشرشراببببرة اىسرذببببرة, ببببرا ا قببببرو اىرشمرضببببرة. اى
عشضرة ىيتخثرش ىيعرذ.
اى بببا ىيشاضبببة سئسببب صبببذس ببب بببذ و عبببائ دببب اىببب اىصبببه شبببو
نببب ببا ببب اىعائببة اىصبببه اقبب . اىنيبب ىغسبببو خضببع اىبببز اىشضبب حسبباء
عيبببا يحفببباظى نببب جبببذ مبببو بببزه أ جببب اىتببب "اىبببث باظبببة اىعقببباسا " بأبببا صبببفا
قببببذ. اىنيبببب غسببببو عيبببب اىتظبببب شيببببى قبببب ثببببشبببب أمثببببش قتببببا باعت اسببببا
جشاحبببة ببب تفاتبببة اىنيببب غسبببواىبببذ و اىعبببائ ىي عيببب ىيحفببباظ تقبببا عبببذة صبببف
.ج ض أحاا اىجيذ طش ع ىتيل اىت تت فتحة
ا س بببراء ىفشبببرو اىصبببر اىشرشرابببرة اىسرذبببرة بببر اىتضبببر اىترضابببرذ برسبببرذ
اىصيرة اىشرشرارة اىسرذرة ىيتخثرش اىرذر.
ا بببببرئ بببببرذه رشاق بببببرة بببببز اىصببببب بببببر االمتشبببببراه اى نبببببرش ىيتضبببببر زىبببببر
ىرعرائر.تقرر ق رو أ حرذث تخثرش ىيرذ باىرصره ا
ا ىيقسبببطشة اىتذا يبببة ضابببا عبببذة عببب اىتبببذ و اىجشاحببب قببب عاىجبببة اىتضببب بسبببذ أ
شببببشا اىصببببية اىشببببشاة اىسذببببة اىصببببحبة بتغببببش سببببىج أ ظفبببب ببببا اببببا
غببش ختشقببة سبب ا, تحتببا ىقبب أقببو, احتبباال حببذث عببذ بنتشببة أقببو, تحببا ع عيبب
تنببب اىبببش ببب االسبببتخذا اىفبببس ىيصبببية اىشبببشاة اىسذبببة ببب أسدة اىبببش
عية اىغسو اىني.
الوريدية من اجل الغسيل -دراسة ألسباب عدم نضج الوصمة الشريانية الكموي
مقدمه من
دمحم محمود عبد الرحمن مرسي هواري
توطئة للحصول على درجة الماجستير
في الجراحة العامة
كمية الطب جامعة الفيوم
5102
الوريدية من اجل الغسيل -دراسة ألسباب عدم نضج الوصمة الشريانية الكموي
توطئة لرسالة ماجستير الجراحة العامة الرسالة للطبيب
دمحم محمود عبد الرحمن مرسي هواري بكالويوس الطب والجراحة
المشرفون
أ.د أيمن عيسوي الدموية والجراحة العامة أستاذ جراحة األوعية
كلية الطب, جامعة الفيوم
د/ دمحم المعداوي أستاذ مساعد جراحة االوعية الدموية والجراحة العامة
كلية الطب, جامعة القاهرة
د/ صالح سعيد سميمان مدرس الجراحة العامة
كلية الطب, جامعة الفيوم
قسم الجراحة العامة كلية الطب جامعة الفيوم
1025