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

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