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INTRODUCTION — After surgical creation, the vein destined to become a successful arteriovenous fistula (AV) fistula undergoes a remodeling process that is referred to as maturation. Although somewhat variable, these changes occur relatively rapidly, resulting in a fistula that can be repetitively used and that can provide adequate dialysis treatments.
Fistula maturation and the examination of the newly created hemodialysis AV fistula are reviewed here. Failure of maturation (early failure) and late failure of the hemodialysis arteriovenous fistula are reviewed separately. (See "Primary failure of the hemodialysis arteriovenous fistula" and "Failure of the mature hemodialysis arteriovenous fistula".)
FISTULA DEVELOPMENT — Once an arteriovenous (AV) fistula is created, the blood vessels involved (both artery and vein) are subjected to marked changes in hemodynamic forces that trigger vascular remodeling. Blood flow must increase to a level that provides an adequate delivery to the dialysis machine. In addition, the vessel must increase in diameter to accommodate cannulation, and the vessel wall must thicken to permit repeated cannulation. The endpoint of this process is referred to as AV fistula maturation, which can be characterized physiologically using parameters related to blood flow, vessel diameter, and vessel wall thickness . However, the successful clinical use of a newly created AV fistula for hemodialysis is also affected by patient-specific factors that determine its accessibility for cannulation, such as position on the patient's extremity and fistula depth, among others.
Stages — The goal of AV fistula creation is to achieve a vascular access that can be repetitively used for effective, efficient hemodialysis. Conceptually, the process of AV fistula development can be thought of as evolving through three stages:
●Stage I: Creation of a patent AV fistula – An AV fistula is created by suturing together a feeding artery to a nearby vein. To provide the best chance that the fistula will develop, these vessels must be of adequate size, and the vessels leading to and from them must be without areas of stenosis. (See "Creating an arteriovenous fistula for hemodialysis", section on 'Patient evaluation prior to access placement' and "Patient evaluation and vascular mapping prior to placement of hemodialysis arteriovenous access".)
Immediately upon institution of blood flow in the newly created AV fistula, the reduced vascular resistance generates increased flow. In one study involving newly created radiocephalic AV fistulas , a successful AV fistula was characterized by an immediate increase in flow rate (Qa) of 549 percent. This flow-mediated vascular remodeling is a consequence of responses to shear and hoop (circumferential) stress, which govern outflow vein dilatation and wall thickness, respectively . (See 'Physiology of maturation' below.)
●Stage II: Physiologically mature AV fistula – The stage II physiologically mature AV fistula is defined as a fistula that has the potential for being used clinically as a dialysis vascular access. A standardized definition does not exist; however, two interrelated parameters, access vein internal diameter and access blood flow (Qa), are the most easily assessed and have been the most frequently reported. (See 'Measures of maturation' below.)
Clinical definitions of physiologic maturity (eg, an AV fistula that can be repetitively cannulated and that provides adequate blood flow for dialysis) require that the AV fistula is used. It is important that the physiologic maturation of a newly placed AV fistula is evaluated even though immediate use is not anticipated. Due to the high primary failure rate, a salvage procedure may be required to ensure that the access is ready when it is needed and to avoid the use of a central venous catheter for hemodialysis. This problem is particularly apparent in the older chronic kidney disease patient group (>70 years), which is a rapidly growing segment of the dialysis population. In a study of 3418 older patients, 33 percent had an AV fistula placed but had not yet initiated dialysis after a two-year period .
●Stage III: Clinically functional AV fistula – For an AV fistula to be clinically usable, it must be physiologically mature; however, maturation alone is not enough. Appropriate AV fistula depth, length, and location, which contribute to successful cannulation, are critically important. Since not all of these features can be objectively quantified, the main condition that defines a clinically functional AV fistula is a demonstration of usability, which can only be confirmed when the AV fistula is tested in the dialysis facility and has been successfully repeatedly cannulated. (See 'Timing' below.)
Physiology of maturation — AV fistula maturation is dependent on vascular remodeling, which is the structural rearrangement of endogenous and vascular matrix to produce an increase in the lumen area in the case of a successful AV fistula. This process is triggered by increases in shear and hoop stress coupled with the homeostatic principle that the perturbed system attempts to return to its baseline stress state. At the time of creation of an AV fistula, there is a substantial increase in blood flow in the feeding artery due to the decrease in downstream resistance as blood is shunted into the vein. This results in an increased wall shear stress.
Normal blood flow is fastest at the center of the vessel and slowest close to the wall; this is referred to as laminar flow. This is the result of friction between the fluid (blood) and the vessel wall. This friction, exerted by the flowing fluid, creates a force parallel to the vessel wall, which is referred to as the wall shear stress. Its magnitude depends upon the differences in blood velocity at the center of the vessel relative to the boundary layer. In the normal homeostatic state, wall shear stress is low; however, with increasing flow there is a proportional increase in wall shear stress.
At a biologic level (based upon arterial studies), high wall shear stress rates result in the secretion of mediators by the endothelium, such as nitric oxide and prostacyclin, that promote vasodilation and inhibit thrombosis and platelet aggregation [4-8]. It is presumed that a similar mechanism operates on the venous side. Wall shear stress is inversely proportionate to vessel diameter. Therefore, as the diameter of the vessel increases, shear stress is restored to baseline levels.
Hoop stress is also perturbed by the hemodynamic changes that occur with AV fistula creation; however, it has not been subject to as much study as shear stress. With the increase in diameter and blood pressure, hoop stress increases. To restore hoop stress toward its baseline conditions, the thickness of the wall of the vein increases [1,9].
It is important to realize that the changes occur in the artery feeding the fistula as well as the vein that becomes the AV fistula . Failure of arterial maturation can also result in failure of the AV fistula.
PHYSICAL EXAMINATION FOR MATURITY — Physical examination alone is an easy, economical, and very good tool for assessing the maturation of a newly created fistula but requires familiarity with some very basic principles [11,12]. The physical examination should take into account the diameter, depth, and length of the access to be cannulated; subjectively, whether or not the access can be cannulated; and, if so, whether it can be cannulated repetitively. (See "Creating an arteriovenous fistula for hemodialysis", section on 'AV fistula requirements for use'.)
If the arteriovenous (AV) fistula is judged to be mature and the patient has already initiated dialysis, plans can be made to transition to its use.
Clinical evaluation can also detect the site and nature of problems that may be impeding fistula maturation and is the first step in determining the reason and initiating a plan to salvage the access [12,13]. (See 'Failure to mature' below.)
Timing — Studies of AV fistula maturity suggest that whether or not an AV fistula will become clinically usable for dialysis is apparent relatively early in the postoperative period [2,11,14-16]. Based upon these studies, a newly created AV fistula should be evaluated clinically for maturation no later than four to six weeks following surgery [17,18]. Because these patients are either at risk of having to start dialysis with a catheter or are already dialyzing with a catheter, waiting a longer period of time is difficult to justify.
Physiologic maturation occurs quite rapidly. However, recommendations on exactly when is the best time to initiate use of the fistula vary. Kidney Disease Outcomes Quality Initiative (KDOQI) Vascular Access Guidelines recommend that the AV fistula should be used as soon as its diameter and blood flow are adequate but generally not sooner than one month based on the potential for complications :
●In one study, volume flow rate increased by 549 percent on the first day after successful creation of a radial-cephalic AV fistula and by 1189 percent on day 28 .
●In a longer-term study, compared with the initial increases seen at one month, neither volume flow rate nor vessel diameter measurements changed significantly in the second, third, or fourth month after AV fistula creation .
●Data collected by the Dialysis Outcomes and Practice Patterns Study (DOPPS) found no significant difference in AV fistula survival whether the AV fistula was first cannulated within 15 to 28 days or had a longer maturation period of 43 to 84 days . However, AV fistula cannulation within 14 days of creation was associated with a 2.1-fold increased risk of subsequent AV fistula failure compared with AV fistulas cannulated at more than 14 days.
Examination routine — The physical examination of a newly created AV fistula is facilitated by following a systematic routine . Abnormalities may be detected at each step in the routine examination. Typical lesions associated with hemodialysis AV fistulas, including preexisting venous stenosis, juxta-anastomotic arterial stenosis, and accessory vein, are described separately. (See "Primary failure of the hemodialysis arteriovenous fistula", section on 'Associated lesions'.)
Examine the arteriovenous anastomosis — Feel for a thrill and a pulse. The pulse of the fistula should be soft and compressible. A strong thrusting pulse (ie, hyperpulsatile) indicates the presence of a downstream (ie, in the direction of flow) problem creating increased resistance. If there is no thrill or pulse, the AV fistula may be thrombosed or "dead." It may be difficult to resuscitate a thrombosed AV fistula; however, before concluding that function is totally absent, listen with a handheld continuous wave Doppler device. Even if the AV fistula is thrombosed, salvage may be possible if too much time has not elapsed. (See "Primary failure of the hemodialysis arteriovenous fistula", section on 'Thrombosis of newly created AV fistula'.)
It is helpful to listen to the bruit (the auditory manifestation of flow) to determine the character of the diastolic component. The bruit should have a low rumbling pitch with a prominent diastolic component. With progressively increasing resistance (as with stenosis), this component, occurring at the lowest pressure in the cardiac cycle, will disappear first when a lesion is present downstream (ie, in the direction of flow). In addition, the pitch will generally become higher.
Check for the presence of a juxta-anastomotic stenosis, which can be easily diagnosed by palpation of the anastomosis of the artery and distal vein. The stenosis itself can frequently be felt as an abrupt diminution in the size of the vein, almost like a shelf. The effect of the lesion is to obstruct AV fistula inflow. Since it occurs early, it results in primary failure. Normally, a very prominent thrill is present at the anastomosis. The thrill, which is normally continuous, is present only in systole. In some instances (severe lesion), it may be very short and even difficult to detect. As one moves up the vein from the anastomosis with the palpating finger, the pulse goes away rather abruptly once the site of juxta-anastomotic stenosis is encountered. Downstream, the pulse may be very weak and may be difficult to detect.
Evaluate the body of the fistula — Inspect the body of the AV fistula to determine if it is visible and, if so, for what length. Optimal length is 6 to 10 cm. Assess its apparent diameter and depth to determine if it has the potential for being cannulated repetitively. The optimal depth is within 1 cm of the skin surface, preferably approximately 0.5 cm (0.6 cm per the NKF/KDOQI guidelines). (See 'Measures of maturation' below.)
Feel for a pulse, being careful in doing so not to compress the vein and create a spurious one. The AV fistula should be soft and easily compressible. The presence of a strong pulse is an indication of downstream (direction of flow) obstruction of some degree. The severity will be proportional to the degree that the pulse is increased.
Evaluate for one or more accessory veins, which are frequently visible. If they are not visible, they can usually be detected by palpating the AV fistula. The thrill that is palpable over the arteriovenous anastomosis should disappear when the outflow vein is manually occluded more proximally due to cessation of flow. If the thrill does not disappear, then an outflow channel (accessory vein) is present distal to the point of occlusion. Palpation of the AV fistula below the occlusion point will generally reveal the location of the accessory vein by the presence of a thrill over it. By moving the site where the AV fistula is occluded progressively proximally, the entire length of the outflow vein can be evaluated in this manner. A handheld continuous wave Doppler can also be used to evaluate for flow in the accessory vein.
Evaluate for pulse augmentation — When the AV fistula is manually occluded, the arterial pulse distal to the arteriovenous anastomosis should be increased (augmented). The degree of augmentation is directly proportional to the AV fistula flow. With experience, the result of this maneuver can be quantitated on a scale (eg, 1 to 10), serving as a very useful guide to inflow evaluation. If the AV fistula is hyperpulsatile (an indication of outflow stenosis), the change in pulse produced by manual occlusion reflects the severity of stenosis that is causing the hyperpulsatility.
Accuracy — Physical examination alone has been shown to be very accurate for assessing for AV fistula maturation or problems with the fistula and is not difficult to learn [11,21-27]. An experienced clinician (physician, dialysis nurse) can examine a newly created hemodialysis AV fistula and predict with a high degree of confidence its usability as a dialysis access. In one study, experienced dialysis nurses were 80 percent accurate in predicting the usability of an AV fistula for dialysis .
In a prospective study of 142 consecutive patients who were referred for AV fistula dysfunction, the accuracy of physical examination for detecting stenotic lesions was compared with the results of a fistulogram . There was strong agreement between physical examination and fistulography in the diagnosis of inflow and outflow stenosis. The sensitivity and specificity for the outflow and inflow stenoses were 85 and 71 percent, and 92 and 86 percent, respectively. There was also a significant level of agreement regarding the diagnosis of coexisting inflow-outflow lesions between physical examination and fistulography.
In a cohort study of 100 patients, ultrasound flow measurements at one dialysis unit were compared with physical examination at another . For the clinical cohort, a fistulogram was obtained for a change in the access appearance, a change in the bruit, or a sharp increase in venous resistance. A fistulogram was obtained in the ultrasound flow cohort for graft flow less than 600 mL/minute, fistula flow less than 450 mL/minute, or flow decreased more than 25 percent relative to baseline. Primary patency rates were not significantly different between the clinical and ultrasound flow groups (1199 versus 1162 days). The mean number of procedures, including angiographic procedures, to achieve maturity were also similar, with 56 percent of all patients requiring none.
MEASURES OF MATURATION — Physical examination of the newly created arteriovenous (AV) fistula by an experienced practitioner has a greater than 80 percent accuracy for predicting AV fistula maturation [11,28]. Nonetheless, physical parameters are often used in conjunction with physical examination. These include AV fistula internal diameter and volume flow rate, typically as assessed using ultrasound [11,21,29].
The "rule of 6s" describes parameters associated with maturity of a newly created AV fistula as set forth by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for dialysis access . The rule of 6s states that 6 weeks after the AV fistula has been placed, the fistula is more likely to be usable if:
●The external diameter is greater than 0.6 cm
●The fistula is no more than 0.6 cm deep from the skin surface
●Blood flow rate is greater than 600 mL/minute
If an AV fistula meets these targets, it likely to be usable. However, although the rule of 6s is used, the quality of evidence for the values listed above is weak, provided all other things, such as proper position, and length are acceptable. The author often uses an internal diameter >0.4 cm for determining when to initiate AV fistula use based upon the data discussed in the next several sections.
Diameter — The access vein diameter is defined as the inner diameter of the vein in the actual or prospective cannulation zone . This vein needs to be of an optimal diameter not only for ease in needle placement but also for providing adequate blood flow. The most frequently quoted value for this parameter is 0.6 cm, used in association with the "rule of 6s" . However, an AV fistula that has not attained this value may also be usable. Some studies support a lower diameter. An upcoming publication from The American Society of Nephrologists Kidney Health Care Initiative – Endpoints for Trials Involving Dialysis Vascular Access – Committee on Fistulas is expected to support an alternative threshold, but, again, the quality of evidence for any diameter value is overall low .
●In a multicenter study of 602 (180 women and 422 men, 459 with upper-arm AV fistulas and 143 with forearm AV fistulas) AV fistulas, the draining vein diameter was assessed using ultrasound postoperatively after one day, two weeks, and six weeks . Mean AV fistula diameters of at least 0.4 cm were seen at one day, two weeks, and six weeks in 85, 91, and 87 percent of upper-arm AV fistulas and 40, 73, and 77 percent of forearm AV fistulas, respectively. Two-week AV fistula diameters were more accurate in predicting six-week values compared with those obtained on the first day.
●In a smaller study that assessed the adequacy of dialysis in 54 patients, the mean vein inner diameter was 0.49 cm for successful AV fistulas and 0.34 cm for unsuccessful AV fistulas . A minimum AV fistula internal diameter >4 mm was determined to be the optimal threshold for predicting a successful AV fistula. This diameter had an accuracy of 72 percent and a sensitivity and specificity of 75 and 75 percent, respectively. For AV inner diameter >0.4 cm, adequacy for dialysis occurred in 89 percent of AV fistulas, whereas for venous diameter <0.4 cm, only 44 percent were judged adequate.
●A review involving 119 AV fistula cases also looked at the sensitivity of diameter measured four weeks after AV fistula creation for predicting successful use of newly created AV fistulas . They found an optimal internal diameter of 0.5 cm using receiver-operator curve (ROC) analysis. This value included both upper-arm and forearm AV fistulas.
●However, in another study, there was no significant difference in the diameter of AV fistulas that matured without problems and those that had a primary failure (0.42 versus 0.39 cm) . When analyzed by type of fistula (brachiocephalic or radiocephalic), there were also no significant differences.
Volume flow rate — The ideal volume flow rate that suggests maturity of an AV fistula is not known for certain. The volume flow rate reported in normally functioning AV fistulas ranges from 352 to 500 mL/minute . A volume flow rate less than 400 to 500 mL/minute has certainly been associated with a risk for AV fistula thrombosis [18,34-36].
In a survey of dialysis facilities by the United States Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor, the average dialysis blood flow rate was 417 mL/minute (median 400 mL/minute) . To be considered mature, the flow rate in an AV fistula should exceed this level by at least 100 mL/minute to avoid recirculation. The parameter from the KDOQI rule of 6s is 600 mL/minute ; however, the quality of evidence supporting this value, or any other value, is overall low [11,21,29]. Others have suggested a lower minimum value of 500 mL/minute as an acceptable flow rate for initial cannulation attempts .
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. Such a perioperative index would 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 [38,39].
●In one study, a value >120 mL/minute had a sensitivity of 67 percent, specificity of 75 percent, and positive predictive value of 91 percent .
●In another study involving radiocephalic AV fistulas, blood flow volume was measured one week postoperatively . The functional fistulas had a mean flow of 753 mL/minute, and nonfunctional fistulas had a mean flow of 121 mL/minute. In this study, no fistula with a blood flow <200 mL/minute at one week reached maturity without requiring a procedure to assist maturation. This threshold provided a sensitivity of 98.5 percent and a specificity of 12.9 percent, with a positive predictive value of 36.8 percent and a high negative predictive value of 94.4 percent.
●In a multicenter study of 602 (180 women and 422 men, 459 with upper-arm AV fistulas and 143 with forearm AV fistulas) AV fistulas, blood flow rates were measured using ultrasound postoperatively after one day, two weeks, and six weeks . Among fistula patients who did not experience thrombosis or the need for AV fistula intervention prior to six weeks, at least 50 percent of the six-week blood flow rate measurement was achieved at one day. Two-week AV fistula flow rates were more accurate in predicting six-week values compared with those obtained on the first day.
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 . This phenomenon has been used as an index to predict maturation of an AV fistula. In a study involving 46 AV fistulas, including both radiocephalic 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 . 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 .
Combination of flow and diameter — A single study has evaluated the predictive value of combining flow and vessel diameter . This study showed that combining both metrics (Qa of ≥500 mL/minute and internal diameter of >0.4 cm) enhanced the predictive value for fistula maturation. When both Qa and internal diameter thresholds were met, 95 percent of the fistulas were adequate for dialysis; when neither threshold was achieved, only 33 percent of fistulas were adequate. Achieving only the minimum AV internal diameter threshold showed 67 percent of AV fistulas as being adequate, and achieving only the minimum Qa threshold resulted in 70 percent of AV fistulas being adequate.
Vein wall thickness — Although very little has been published on the subject, it has been proposed that increased hoop stress, which is a characteristic of an immature fistula, increases the risk of extravasation with cannulation of an immature AV fistula. Increasing vein wall diameter decreases hoop stress toward baseline levels. Based upon this premise, a study was conducted to determine if this metric could be used as a proxy for determining AV fistula maturation . Using high-frequency ultrasound (>30 MHz), a vein wall intimal-medial layer thickness threshold of 0.13 mm was indicative of AV fistula maturation as judged by ability to cannulate without extravasation. However, this approach requires the use of high-frequency ultrasound, which is not generally available; conventional ultrasound imaging systems typically use a maximum frequency of 15 MHz, which does not provide adequate spatial resolution.
FAILURE TO MATURE — Failure of maturation is a major problem. We define early failure as an AV fistula that is never usable for dialysis or that fails within three months of use [15,44]. 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.
Access history — Basic information will help define potential problems and will immediately raise possibilities for the cause of arrested maturation.
●How long has it been since the AV fistula was created? An AV fistula that appears more mature than its actual age might have a proximal venous outflow stenosis.
●Knowing the type of AV fistula is helpful as different types of AV fistulas have a predilection for certain types of problems. This is especially true for the "swing-point" stenoses [45,46]. (See "Creating an arteriovenous fistula for hemodialysis", section on 'Types of native AV fistulas' and "Primary failure of the hemodialysis arteriovenous fistula", section on 'Associated lesions'.)
●If attempts have been made to use the AV fistula, the "use history" can be very important. Was the problem difficulty with cannulation? Or was the flow inadequate? (See "Clinical monitoring and surveillance of the mature hemodialysis arteriovenous fistula".)
Further evaluation — If the newly created arteriovenous fistula is not maturing or any abnormalities are identified on physical examination, the AV fistula should be evaluated further as soon as possible, usually using duplex ultrasound and/or contrast angiography. Duplex ultrasound is very useful for the evaluation of a newly created AV fistula [11,47-49]. However, there is generally no need for performing ultrasound unless the physical examination reveals a problem . Using ultrasound, blood flow and vessel diameter can be measured, and suspected anatomic lesions can be further defined. Although ultimately the most accurate diagnosis and localization relies on angiography, the information obtained by duplex examination of the fistula can be valuable to help plan salvage, if indicated, using interventional techniques. Lesions that may delay fistula maturation are often multiple. Unless associated with thrombosis, total occlusion, or certain preexisting lesions, which should have been identified preoperatively with good vascular mapping, the lesions associated with lack of maturation can generally be corrected, resulting in salvage of the AV fistula with a high expectation of success . (See "Primary failure of the hemodialysis arteriovenous fistula".)
SUMMARY AND RECOMMENDATIONS
●A thorough evaluation of a new arteriovenous (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 than four to six weeks 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 'Physical examination for maturity' above.)
●The goal of hemodialysis AV fistula creation is to achieve a functioning 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. A minimum fistula diameter of 0.4 cm combined with a minimum flow volume of 500 mL/minute predicts a high level of fistula usability. The fistula must also be accessible and within 1 cm of the skin surface, ideally approximately 0.5 cm with a straight segment that is 6 to 10 cm in length. (See 'Fistula development' above.)
●Optimal AV fistula development at four to six weeks can generally be recognized by physical examination by an experienced person. This examination should be systematic and follow an established algorithm in order to assure a complete and thorough evaluation. In cases in which vascular mapping has been done and followed, the cause of failure to develop is generally present, is detectable by physical examination, and can generally be addressed in a manner that results in AV fistula salvage. (See 'Physical examination for maturity' above.)
●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. (See 'Failure to mature' above.)
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