Early evaluation of the newly created hemodialysis arteriovenous fistula

INTRODUCTION — The goal of hemodialysis arteriovenous (AV) fistula creation is to achieve a functional dialysis access. This means that the AV fistula must be of adequate size to allow for successful repetitive cannulation and provide adequate blood flow to support the hemodialysis prescription.

The evaluation of the newly created hemodialysis arteriovenous fistula for development and maturation and to identify correctable problems to improve maturation and longevity is reviewed. (See "Primary failure of the hemodialysis arteriovenous fistula" and "Failure of the mature hemodialysis arteriovenous fistula".)

Creation of the AV fistula and complications are reviewed separately. (See "Arteriovenous fistula creation for hemodialysis and its complications".)

DEVELOPMENT PHASES AND PROBLEMS — Evolving from creation to loss of function, changes occurring with an AV fistula can be divided into five phases: creation, maturation, initial clinical use, sustained clinical use, and dysfunction (figure 1) [1].

Phase 1: fistula creation — Phase 1 is characterized by the creation of a patent AV fistula using open surgery (sAV fistula) or a percutaneous approach (pAV fistula). (See "Arteriovenous fistula creation for hemodialysis and its complications" and "Percutaneous hemodialysis arteriovenous fistula".)

To create an AV fistula, an anastomosis is made between a feeding artery and an outflow vein to provide access to the bloodstream for hemodialysis [1]. The endpoint of AV fistula creation is either success or failure, which will be immediately apparent. The success of AV fistula creation is confirmed by demonstrating blood flow throughout the venous component of the intended course of the AV fistula [2]. Examination of the newly created AV fistula by the clinician who created the access is recommended to assess for complications within two weeks of its creation [3].

Early thrombosis — Although salvage may be possible if too much time has not elapsed [4,5], a major cause of primary failure of newly created AV fistulas that cannot be salvaged is early thrombosis. (See "Primary failure of the hemodialysis arteriovenous fistula", section on 'Thrombosis of newly created AV fistula'.)

In a study derived from 11 centers, among 428 AV fistulas with known outcomes, 171 (40 percent) had primary failure. Of these, only 44 (26 percent) could be salvaged [6]. Early thrombosis was the cause in 61 (35.6 percent). In the Hemodialysis Fistula Maturation Study, which was a prospective, multicenter, cohort study, early thrombosis occurred in 32 of 602 study participants (5.3 percent) [7]. Early thrombosis was associated with female sex (odds ratio [OR] 2.75, 95% CI 1.19-6.38), fistula location (forearm versus upper arm, OR 2.76, 95% CI 1.05-7.23), feeding artery (radial versus brachial, OR 2.64, 95% CI 1.03-6.77), arterial diameter (OR 1.52, 95% CI, 1.02-2.26; per 1 mm smaller), and draining vein diameter of 2 to 3 mm. An absent or attenuated intraoperative thrill and surgeon frustration and concern about successful maturation during surgery correlated strongly with early thrombosis. The risk of early thrombosis was higher when protamine was used to reverse the heparin effect than when heparin was used without reversal during the surgical procedure. Of interest was the fact that there was a decreased frequency of early thrombosis in those with diabetes, occurring in 2 percent of those with diabetes compared with 10 percent of those without.

Hemodialysis access induced distal ischemia – Hemodialysis access-induced distal ischemia (HAIDI) can appear immediately upon the creation of an AV access. In a systematic review among 464 cases of HAIDI, acute HAIDI (occurring immediately after surgery or within hours) was seen in 104 cases [8]. While most of these occurred in association with an AV graft, 13 percent were in patients with an AV fistula. (See "Hemodialysis access-induced distal ischemia".)

Phase 2: maturation — Phase 2 is characterized by the development of a physiologically mature AV fistula, which has been defined as an AV fistula having a minimum internal vessel diameter that is ≥0.5 cm and a blood flow that is ≥500 mL/min [1]. These metrics can generally be adequately defined using Doppler ultrasound, with blood flow being assessed from the brachial artery. (See 'Measures of maturation' below.)

Once an AV fistula is created, the involved blood vessels (both artery and vein) are subjected to marked changes in hemodynamics that trigger vascular remodeling. Blood flow must increase to a level that provides adequate delivery to the dialysis machine. In addition, to accommodate repeated cannulation, the vein must increase in diameter, and its wall must increase in thickness [9].

Physiology of maturation — A substantial increase in blood flow occurs in the feeding artery at the time of AV fistula creation due to the decrease in outflow resistance as blood is shunted into the vein. This increase in blood flow initiates responses that lead to vessel remodeling.

For an AV fistula to successfully mature after creation, functional and structural adaptations to the inflow artery and outflow vein must occur [9-14]. The marked increase in blood flow in the vein results in a proportional increase in wall shear stress (WSS), which stimulates endothelium-dependent vasodilation in the feeding artery in the outflow vein, mediated primarily by nitrous oxide and activation of matrix metalloproteinases (MMPs). This dilates both vessels and inhibits neointimal hyperplasia. WSS is inversely proportionate to vessel diameter. Therefore, as the diameter of the vessel increases, WSS decreases. Upregulation of MMPs results in matrix degradation and restructuring of the vascular scaffold, leading to luminal expansion. Arterial and venous remodeling restores WSS toward normal levels in the face of increased blood flow that helps maintain luminal diameter, the hallmark of the outward remodeling that characterizes a mature AV fistula [14]. It is important to realize that these changes occur in the artery feeding the fistula as well as in the vein that becomes the AV fistula. Failure of arterial maturation can also result in failure of the AV fistula [15].

Problems with maturation — A major problem occurring in the second phase of AV fistula development is failure of the AV fistula to mature. Failure to mature is defined as an AV fistula that is never usable for dialysis or that fails within three months of use [4,5]. In one multi-institutional review, inadequate maturation occurred in 29 of 171 (17 percent) [6]. The AV fistula that has failed to mature generally has an anatomic problem of some type that can be identified by physical examination and confirmed by imaging.

In general, problems with the AV fistula can be classified as either an inflow or outflow problems. These can be anatomically related or lesions that existed prior to the creation of the AV fistula or acquired after surgery (perhaps related to the surgical technique). Lesions that may delay fistula maturation may be multiple [4]. Lesions can generally be corrected, resulting in salvage of the AV fistula with a high expectation of success, unless associated with thrombosis, total occlusion, or with certain preexisting lesions [16].

Many of the potential problems can be largely avoided by good patient evaluation and selection (risk factors), vascular mapping prior to access creation, and good surgical technique. (See "Arteriovenous fistula creation for hemodialysis and its complications", section on 'Evaluation and planning'.)

Phase 3: initial clinical use — Phase 3 is characterized by an AV fistula that can be used for dialysis, and is defined as an AV fistula that can be cannulated with two dialysis needles and achieve the prescribed dialysis [1]. The goal of AV fistula creation is to have an AV fistula that can be repeatedly cannulated easily with the longest possible use-life. An AV fistula can be physiologically mature but still may not be usable. In addition to the criteria required for maturation, the clinical usability of an AV fistula depends on patient-specific criteria such as AV fistula depth, length, and location which allow the AV fistula to be successfully and repeatedly cannulated.

To facilitate this goal, the AV fistula should be located on the anterior or lateral surface of the upper arm, or the volar surface of the forearm. Because of the length of the standard dialysis needle and to assure ease of cannulation, the optimal depth should be <0.5 cm. To facilitate a site-rotation (ie, rope–ladder) cannulation protocol, we feel that the cannulation zone should be >10 cm (figure 2). Although an AV fistula that does not meet all of these criteria may function as a hemodialysis access, it represents a compromise and is susceptible to problems.

Phase 4: sustained clinical use — Phase 4 is defined as continuous, effective, problem-free use of the AV fistula for hemodialysis. It begins once the AV fistula is deemed to be clinically functional and represents the ultimate criteria for judging success. Unfortunately, most patients will alternate between phase 4 and phase 5 (ie, dysfunction). The duration of phase 4 is indeterminate, limited only by the occurrence of problems and complications. In a meta-analysis of studies evaluating AV fistula patency, the primary patency rate (ie, AV fistula does not move to Phase 5) was 60 percent at one year, and 51 percent at two years [17].

Phase 5: dysfunction — Phase 5 is defined as the occurrence of any problem that: interferes with the routine use of the AV access; threatens patency or results in a loss of patency; presents a significant risk of medical complication; or adversely affects the patient’s sense of wellbeing. If the attributable problem can be resolved, the AV access returns to Phase 4. Limiting the time spent in Phase 5 is an important goal and timeliness in addressing problems is critically important. If an AV fistula cannot be salvaged and returned to Phase 4, it is lost.

In a Dialysis Outcomes and Practice Patterns Study international study, Japan had the highest cumulative patency with 87 and 81 percent of AV fistulas remaining patent at 6- and 12 months post-creation, respectively [18]. Europe, Australia, New Zealand, and the United States displayed nearly identical patterns of cumulative patency, with approximately 80 and 70 percent patent at 6- and 12 months post-creation, respectively.

EVALUATION — Based upon clinical evidence and experience, evaluation of all newly created AV fistulas at four to six weeks to determine maturation should be considered mandatory [3]. This is based upon the observation that an AV fistula that does not appear to be mature at this timeframe will generally not become adequate later without intervention [19,20]. Waiting longer than four to six weeks increases the risk of the patient either starting dialysis with a catheter or continuing its use if the patient is already on dialysis.

In cases in which vascular mapping was performed, the cause of thrombosis or failure to develop may have already been noted, is detectable by physical examination, and can generally be addressed in a manner that results in AV fistula salvage.

Obtain access history — The evaluation of the AV fistula begins by gathering pertinent information. A poorly developed AV fistula may not be apparent on first examination. The examiner may have to ask the patient where the access is located as well as when it was created. If the AV fistula has not or is poorly developed, the physical examination should focus on determining the cause for development failure. In addition, it is helpful to know if there were any attempts to use the AV fistula, and if so, if and what sort of problems may have been encountered. Any changes that the patient may have noticed can also be very helpful in making the assessment.

Physical examination — The recommended objective criteria for determining maturation involves ultrasound evaluation (see 'Measures of maturation' below) [1]. However, physical examination is not difficult to learn and used alone has been shown to be very accurate for assessing the AV fistula [2,21-27]. An experienced clinician (eg, nephrologist, dialysis nurse) can examine a newly created hemodialysis AV fistula and predict with a high degree of confidence whether it will be usable as a hemodialysis access [21,28]. In one study, experienced hemodialysis nurses were 80 percent accurate [21]. In addition to determining maturation, identifying pathology that is causing pathology is generally possible with a comprehensive examination of the access [2,20,21,28,29]. Because more than one lesion may be present, a stepwise approach to performing physical examination of the AV fistula is recommended.

There are varying degrees of visual prominence of a newly created percutaneous arteriovenous (pAV) fistula (figure 3). In some instances, the AV fistula is not evident unless a tourniquet is applied proximately over the outflow. This can make the physical examination challenging with respect to determining its characteristics relative to maturation and detecting problems and may additionally pose a challenge placing needles. Tourniquet use is of considerable value to map the cannulation zone using ultrasound when evaluating a newly created pAV fistula for first clinical use. This can be done by marking a dot every centimeter along the course of the cannulation zone under ultrasound visualization and then connecting the dots with a single line which will then lie over the course of the segment to be used for cannulation.

Examine the anastomosis — Problems that may be detected at this step include a thrombosed or "dead" AV fistula, inflow stenosis, outflow stenosis or occlusion, and the presence of a juxta-anastomotic stenosis (JAS).

At the documented location of the AV fistula, feel for a pulse and a thrill, and listen for a bruit using a stethoscope. If there is no thrill, pulse, or bruit, the AV fistula may be thrombosed.

●The pulse of the inflow artery should be palpable, and the fistula should be soft and compressible (figure 4). A strong thrusting pulse suggests (ie, hyperpulsatile) the presence of a outflow problem creating increased resistance. The thrill (figure 5) should be relatively strong and have a both a systolic and a diastolic component. A decreased intensity shortened (absent diastolic component), or absent thrill indicates a problem.

●Upon auscultation with a stethoscope, the bruit should have a low rumbling pitch with a prominent diastolic component (figure 6). With progressively increasing resistance (as with stenosis), this component, occurring at the lowest pressure in the cardiac cycle, will be the first to disappear. In addition, the pitch of the bruit will generally become higher and make take on a whistling character.

The presence of a JAS can be easily identified by palpation of the anastomosis and distal vein. With JAS, the vein at the anastomosis will often be slightly aneurysmal, and a very forceful pulse will be felt at the anastomosis due to the stenosis that is immediately adjacent (figure 7). The thrill will be shortened and may be present only in systole, as is typical for outflow stenosis. In some instances (eg, severe lesion), the thrill may be very short and even difficult to detect. In the presence of a JAS, as the palpating finger moves up the vein away from the anastomosis, the pulse may disappear rather abruptly as the site of stenosis is encountered. Above this level (along the outflow), the pulse is very weak and may be difficult to detect. The beginning of the stenosis can also frequently be palpated as an abrupt diminution in the size of the vein, almost like a shelf. When these typical physical findings of JAS are detected, the cause for poor AV fistula development becomes obvious [30].

Evaluate the body of the fistula — Problems that might affect the development of a clinically usable AV fistula that concern the body of the fistula include an AV fistula that is too deep or of insufficient size or length. In addition, the presence of outflow stenosis should be obvious, and the presence of a significant accessory vein might be discovered.

A stage 2 physiologically mature AV fistula defined by objective demonstration using duplex ultrasound of a minimum access vessel internal diameter ≥0.5 cm and an access blood flow ≥500 mL/min. The duration of this phase is measured in weeks because most AV fistulas that mature will do so in four to eight weeks. (See 'Imaging evaluation' below and 'Measures of maturation' below.)

Feel for a pulse, being careful not to compress the vein and create a spurious pulse. The AV fistula should be soft and easily compressible. The presence of a strong pulse is an indication of outflow obstruction (ie, in the direction of flow). The degree to which the pulse is increased is proportional to the severity of obstruction.

Evaluate for one or more accessory veins, which are frequently visible. If they are not visible, they can usually be detected by performing a sequential occlusion test. This is performed by occluding the AV fistula a short distance above the anastomosis with one hand while feeling for the presence of the thrill at the anastomosis with the other. Because the presence of a thrill depends upon access blood flow, the thrill will disappear when the access is occluded unless there is an ancillary outflow channel (ie, side branch). The test is performed by starting a short distance above the anastomosis and sequentially occluding the access by moving the point of occlusion progressively along the outflow vein. At any point, if the thrill does not disappear, a side branch is present immediately below that point of occlusion (figure 8).

Perform special maneuvers — To complete the examination, perform the pulse augmentation test to evaluate blood inflow and the arm elevation test to check for outflow stenosis.

Pulse augmentation test — When an AV fistula is manually occluded (figure 9), the degree of augmentation is directly proportional to the AV fistula flow. With experience, the result of this maneuver can be quantified on a scale (eg, 0 to 3), serving as a very useful guide to inflow evaluation. If the AV fistula is already hyperpulsatile, which is an indication of outflow stenosis, the degree of change in the pulse with manual occlusion reflects the severity of stenosis.

Arm elevation test — An AV fistula is generally distended when the arm is dependent because of gravity. If the arm is then elevated to a level above the heart, the AV fistula should collapse. This can be taken as evidence that a significant venous outflow lesion is not likely, although an extremely high flow AV fistula can occasionally give a false positive [30]. Even if the patient has a large, dilated AV fistula, it should become flaccid with arm elevation. When a venous stenosis is present, only the portion of the AV fistula proximal to the stenotic lesion (ie, toward the heart, in the outflow segment) will collapse with the arm overhead, while the portion of the AV fistula distal to the lesion (ie, toward the anastomosis in the outflow segment) will remain distended. The arm elevation test is most useful for a forearm AV fistula. For an upper arm AV fistula one may need to assess the “fullness” with simultaneous palpation since the upper arm AV fistula outflow vein is often poorly seen.

IMAGING EVALUATION — If a newly created AV fistula does not appear to be maturing, or if any abnormalities are identified on physical examination, further evaluation as soon as possible is warranted using duplex ultrasound or contrast angiography.

Duplex ultrasound — Duplex ultrasound is very useful for the evaluation of a newly created AV fistula [21,31-33]. Blood flow, vessel diameter, and depth of the AV fistula can be measured, and suspected anatomic lesions can be further defined. However, there is generally no need for performing ultrasound unless the physical examination reveals a problem [23]. (See 'Physical examination' above.)

Lesions associated with dysfunction of the newly created AV fistula that can be identified on ultrasound include:

●Inflow problems – Preexisting arterial pathology (anatomically small artery, atherosclerotic disease); acquired lesions (anastomotic stenosis, juxta-anastomotic stenosis)

●Outflow problems – preexisting venous pathology (anatomically small veins, focal venous stenosis)

●Normal anatomic variations (accessory veins)

●Thrombosis

The information obtained from duplex examination of the AV fistula can be valuable to help plan salvage, if indicated, using interventional techniques.

Measures of maturation — Recommendations for judging AV fistula maturation are based upon ultrasound evaluation. Although not validated, parameters referred to as the "rule of 6s" have been adopted by many as an approach to determining maturity; however, these have not been validated and two of the criteria cannot be determined without the use of ultrasound. In using ultrasound, the internal, rather than the external diameter is measured most easily. The rule of 6s states that six weeks after the AV fistula has been placed, the AV fistula is more likely to be usable if:

●The external diameter is greater than 0.6 cm

●The AV fistula is no more than 0.6 cm deep from the skin surface

●Blood flow rate is greater than 600 mL/minute

The accuracy of vessel diameter and blood flow rate used as measures of maturation either separately or combined has been reported. Based on the available data reviewed below, when evaluating an AV fistula, we prefer to use an AV fistula internal diameter ≥0.5 cm, access depth ideally 0.5 cm from the skin surface and access blood volume flow rate ≥500 mL/min [1].

Diameter — The optimal access vein diameter is defined as the inner diameter of the vein in the actual or prospective cannulation zone [2]. The likelihood of fistula usability increases in proportion to increased diameter [19]. It should also be noted that this access-vessel internal diameter criterion is based upon studies in which the measurements were performed without a tourniquet [2,28,31].

Volume flow rate — In a review of studies relating access blood flow and fistula maturation, a rate of 400 to 500 mL/min had an accuracy of 53 to 93 percent, a sensitivity of 67 to 96 percent, and a specificity of 65 to 90 percent for predicting maturation [1]. Collectively, the available studies suggest a reasonable minimum access blood flow threshold of 500 mL/min for determining AV fistula usability [34].

For AV fistulas that are radial or brachial artery-based, the duplex interrogation site for measuring access blood flow should be in the brachial artery at least 5 cm proximal to the anastomosis [1]. Because of the frequent presence of a high brachial artery bifurcation, care must be taken to ensure that the measurement is being taken from the brachial artery, rather than the proximal radial or ulnar artery.

Blood flow in the AV fistula increases rapidly following surgical creation. Several studies have examined the perioperatively measured volume flows using ultrasound or the pattern of blood flow as an indicator for AV fistula progression to maturation [34-40]. When blood flow in a normal vessel is examined using color-flow Doppler ultrasound with the probe turned to examine the vessel in cross section, it detects the flow going away and toward the probe as a red-blue split indicating a spiral vector. This indicates the presence of spiral laminar flow (SLF) in the vessel. The presence of SLF is considered the normal physiological pattern and is lost in certain disease states [38].

Measurement of blood flow or flow pattern could be useful for early prediction of the AV fistula that is not likely to mature. This would permit early intervention for salvage or replacement and avoid the delay of waiting four to six weeks to determine if maturation has occurred.

●Studies of perioperative blood flow measured 10 minutes after completion of the vascular anastomosis in AV fistulas report thresholds of 120 to 160 mL/minute as a predictor of failure of the AV fistula to mature [37,40].

●The presence of SLF has also been used to predict maturation of an AV fistula. In a study involving 46 AV fistulas, including both radial-cephalic and brachiocephalic fistulas, the presence of SLF had a sensitivity of 82 percent and a specificity of 91 percent for predicting a usable AV fistula at six weeks [39]. In another study of 203 cases involving both forearm and upper-arm AV fistulas, the presence of SLF had a sensitivity of 96 percent and a specificity of 47 percent for predicting a usable AV fistula at six weeks [36].

Combination of flow and diameter — The parameters of access blood flow, vein diameter, and vein depth all influence the usability of the newly created AV fistula. Of these, blood flow and diameter relate to the physiological changes essential for maturation. In a study that used a combination of blood flow and diameter, threshold values of 500 mL/min and 5 mm had a sensitivity of 84 percent and a specificity of 93 percent for the prediction of AV fistula maturation [28].

Contrast arteriography — The most accurate diagnosis and localization of lesions associated with the AV fistula relies on contrast angiography to evaluate the fistula and its inflow and outflow. The utility of contrast arteriography and interventional techniques used to salvage AV fistulas are reviewed separately. (See "Endovascular intervention for the treatment of stenosis in the arteriovenous access" and "Techniques for angioplasty of the arteriovenous hemodialysis access".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis" and "Society guideline links: Hemodialysis vascular access".)

SUMMARY AND RECOMMENDATIONS

●The newly created AV fistula – As a newly created arteriovenous (AV) fistula matures, it must become an adequate size and configuration (depth, length) that allows repetitive cannulation and provides adequate blood flow to support the hemodialysis prescription to achieve a functioning dialysis access. Evaluation of the newly created AV fistula aims to identify correctable problems to improve maturation and longevity. (See 'Introduction' above.)

●History and physical examination

•A thorough evaluation of a new AV fistula four to six weeks after creation should be considered mandatory to assess fistula maturation and to detect problems as early as possible. Waiting longer is generally not necessary and increases the risk of the patient either starting dialysis with a catheter or continuing its use if the patient is already on dialysis. (See 'Evaluation' above.)

•Optimal AV fistula development can generally be recognized by an experienced clinician (eg, dialysis nephrologist, dialysis nurse). The history and physical examination should be systematic and follow an established algorithm to assure a complete and thorough evaluation. Typical inflow (arterial stenosis, juxta-anastomotic stenosis) and outflow lesions (eg, venous stenosis) can usually be detected by physical examination. In cases in which vascular mapping was performed prior to AV fistula creation, a potential problem may have already been noted. (See 'Evaluation' above.)

●Imaging evaluation – If an abnormality is detected in the routine examination of the newly created AV fistula that has failed to mature, the AV fistula should be evaluated further as soon as possible, usually using duplex ultrasound and/or contrast angiography. Problems that are identified can generally be addressed in a manner that results in AV fistula salvage. (See 'Imaging evaluation' above.)

●Measures of maturation – Based on ultrasound criteria, a minimum internal AV fistula diameter of 0.5 cm combined with a flow volume of 500 mL/minute predicts a high level of fistula usability. The fistula must also be accessible on the anterior or lateral surface of the upper arm, or volar surface of the forearm. It should lie within 0.5 cm of the skin of the skin surface, and ideally have a straight segment that is 10 cm in length. (See 'Measures of maturation' above.)