DISEASE OF THE MONTH J Am Soc Nephrol 14: 1669–1680, 2003 Eberhard Ritz, Guest Editor

The Arteriovenous

KLAUS KONNER,* BARBARA NONNAST-DANIEL,† and EBERHARD RITZ† *Merheim Hospital, Medical Faculty, University of Cologne, Germany; †Department of Nephrology, Med. Klinik IV, Erlangen-Nu¨rnberg, Germany; and ‡Department Internal Medicine, Ruperto Carola University, Heidelberg, Germany.

The ground-breaking article by Brescia and Cimino in 1966 (1) side fistula. Flow increased from 21.6 Ϯ 20.8 ml/min to 208 Ϯ revolutionized the creation of the , and the 175 ml/min immediately after operation. In well-developed fistu- Cimino fistula was soon used in almost all dialysis patients. lae, flow rates may ultimately reach values of 600 to 1200 ml/min. Unfortunately, subsequent wide-spread use of PTFE grafts Flow increases as a result of both vasodilation and vascular instead of AV fistulae occurred because of the ease of the remodeling. The latter has been studied using echo-tracking surgical technique, the immediate availability of the graft for techniques (8). It was found that the diameter of the proximal puncture, the need of high blood flow for high-efficiency, antecubital increased progressively while the intima me- short-duration sessions, and because of financial dia thickness remained unchanged. Venous dilation caused disincentives against the AV fistula. PTFE grafts currently reduction of mean shear stress, which had returned to normal account for 80% of primary vascular accesses created in the values by 3 mo. The venous limb of the AV fistula underwent United States (2,3), but they are less frequently used in other excentric hypertrophy as documented by increased wall cross- countries. It has been increasingly recognized that outcomes of sectional area. In parallel, remodeling of the radial was PTFE grafts are poorer. In the DOQI guidelines (4), this has led seen without arterial hypertrophy, despite a marked increase in to the recommendation that AV fistulae should be the first diameter and blood flow (9). option; however, this advice has not been followed uniformly. The changes in blood flow after creation of an AV fistula One impediment may be the astonishingly high rate of primary initiate compensatory responses that have been elegantly eluci- failures of AV fistulae, up to 50% in some centers (4). The dated in experimental models (10). Apart from primarily NO- DOPPS study (Figure 1) documented substantial differences be- mediated vasodilation, adaptive remodeling of the vessel wall is tween survival of PTFE grafts and AV fistulae and differences of induced by reorganization of cellular and extracellular compo- survival of AV fistulae between the United States and other nents, ultimately altering wall geometry. Elevated flow after cre- countries (3). On the basis of our experience, we are of the opinion ation of an AV fistula enlarges the arterial diameter (10). Kamiya that primary failure rates can be substantially improved by atten- and Togawa (11) documented that after creation of a carotid to tion to small but important details of surgical technique. The jugular the flow-loaded artery enlarged until wall DOQI guidelines state that AV fistulae are feasible only in 50% of shear stress had returned to baseline values. This response usually the patients, but we (5) and others (6) found that construction of occurred rapidly, but when extremely high shear stress was in- native AV fistulae is feasible in up to 90%. duced, it required up to 6 mo (12), for example in the monkey iliac It is the purpose of this article (a) to provide some insights into artery subjected to a 10-fold increase of flow. the fascinating cellular biology and pathophysiology underlying Endothelial cells play a central role in adaptive remodeling the vascular adaptation to the creation of an AV fistula and (b) to (13). Shear stress, i.e., the frictional force generated by blood describe some small, often neglected, but important technical flow, acts on the apical cell surface to deform the cell in the details that determine the success of the procedure. It is the direction of blood flow, thus eliciting rapid cytoskeletal re- intention to improve results and to influence patterns of practice. modeling and activating signaling cascades with the conse- quent acute release of nitric oxide (NO) and prostacyclin Vascular Remodeling and Adaptation to High Flow followed by activation of transcription factors, including NF- Wedgewood et al. (7) measured flow rates in the radial artery ␬B, c-fos, c-jun, and SP-1. The mediators of the adaptive before and immediately subsequent to the creation of an end-to- response include integrins, focal adhesion–associated proteins, and stretch-sensitive calcium channels. The crucial importance of endothelial cells is illustrated by the observation (14) that Correspondence to Dr. Eberhard Ritz, Klinikum der Universita¨t/Heidelberg, Medizinische Klinik, Bergheimer Strasse 56A, 69115 Heidelberg, Germany. de-endothelialization eliminates the dilation resulting from an Phone: 49-622191120; Fax: 49-6221162476; E-mail: [email protected] increase of flow. Acute flow-induced endothelial release of 1046-6673/1406-1669 nitric oxide (NO) (15) as well as increased vessel wall cGMP Journal of the American Society of Nephrology content (16) have been documented in high flow models. Copyright © 2003 by the American Society of Nephrology Inhibition of NO by L-NAME interfered with flow-induced DOI: 10.1097/01.ASN.0000069219.88168.39 vascular enlargement (17). 1670 Journal of the American Society of Nephrology J Am Soc Nephrol 14: 1669–1680, 2003

Figure 1. Fistula versus graft survival in patients starting hemodialysis with a permanent vascular access comparing DOPPS results from Europe and United States. Reprinted with permission from reference 4.

The first step of remodeling involves controlled removal of to low-flow conditions, and this was abrogated by endothelin preexistent vessel wall constituents. The arterial wall of an AV receptor antagonists. Under high-flow conditions, there was an fistula exhibits early tears and fragmentation of the internal increased number of PCNA-positive cells in the media, which elastic lamina (18) and enlarged fenestrae (19), increasing again was abrogated by endothelin receptor antagonists. Obvi- arterial distensibility. The loss of the internal elastic lamina ously the responses of the intima to low flow and of the media results from degradation by metalloproteinases, which are re- to high flow are exaggerated. Against this background, it is leased from endothelial cells (20). A role for oxidative stress is remarkable that remodeling is largely appropriate in uremic suggested by the observation that endothelial cells of flow- patients (8,9). loaded carotid stain positive for nitrotyrosine, which is Although not directly related to uremia, the processes underly- indicative of the presence of peroxynitrite (21), and this is ing the development of stenoses in coronary saphenous vein grafts abrogated by administration of L-NAME. The urokinase type are of interest for understanding the development of fistula ste- of plasmin activator is also upregulated. This observation is noses. It is thought that the changes provoking delayed stenoses important, because the plasminogen-plasmin system activates are initiated during surgery and consist of denudation of the pro-metalloproteinases. It is therefore not surprising that non- surface endothelial cells and insudation of granulocytes and selective inhibitors of metalloproteinases diminish flow-medi- monocytes with deposition of fibrin and thrombocyte-containing ated arterial enlargement in a rat AV fistula model (22). thrombi (26). CRP induces a pro-inflammatory phenotype of The involvement of the above systems raises the issue saphenous vein endothelial cells, which is reversible with the whether remodeling is normal or not in uremia. It is well administration of endothelin receptor antagonists (27); of interest known that generation of NO is reduced in uremia (22), and in view of the microinflammatory state of uremia and the role of numerous specific abnormalities have been described in endo- endothelin receptor antagonists in experimental models of uremia thelial cell monolayer cultures (HUVEC) exposed to uremic (25). Interventions interfering with smooth muscle cell accumu- serum: increased ELAM-1 and VCAM expression, increased lation in the neointima further suggest a role of PDGF (28), presence of von Willebrand factor on the extracellular matrix angiotensin subtype AT-1 receptors (29), VEGF (30), and leptin (23), abnormal cell morphology, accelerated growth, and in- (31), among others. creased expression of tissue factor mRNA (24). Platelet dep- One important aspect in the evolution of the AV fistula of osition on extracellular matrix, which had been synthesized in uremic patients is iatrogenic remodeling resulting from punc- the presence of uremic serum, is also increased. Interestingly ture of the AV fistula (32). Puncture displaces tissue, and the an antibody to human tissue factor prevented the increase in defect caused by the cannulation is replaced by a thrombus platelet deposition observed on “uremic” extracellular matrix, causing a slight increase in tissue mass. Even after healing, the a finding potentially relevant for the genesis of fistula stenoses. edges of the puncture hole stay apart as shown by applying There are few formal analyses of vascular remodeling in ure- tattoo marks. This causes cumulative and progressive enlarge- mia. Amann et al. (25) investigated remodeling in first-order ment of the fistula depending on the number of punctures per branches of the mesenteric arteries exposed to high-flow or unit area. This holds true if the cannula does not punch out low-flow conditions. A highly significant increase in intimal tissue, but rather displaces tissue as seen with anti-coring thickness and intimal cell proliferation was noted in arteries of cannulas, in which only the anterior half of such cannulas uremic compared with sham-operated animals when exposed makes sharp cuts. J Am Soc Nephrol 14: 1669–1680, 2003 The Arteriovenous Fistula 1671

There are three options for cannulation (Figure 2); (a) the tive. If difficulties arise, the hand should be warmed by a hot rope ladder pattern, (b) the area puncture pattern, and (c) the bath. buttonhole pattern. In the rope ladder pattern, the punctures are There is no consensus on the optimal timing of fistula regularly distributed along the entire length of the arterialized surgery. The DOQUI guidelines recommend to establish vas- vein. In contrast, with the area puncture technique they are cular access when the serum creatinine concentration exceeds restricted to a small area. With the buttonhole technique, punc- 4 mg/dl and the estimated GFR is Յ 25 ml/min (4); at any rate, tures are always performed through the exactly identical spot. at least 3 to 4 mo before the scheduled beginning of dialysis. This procedure displaces the thrombus undergoing organiza- One serious impediment to timely creation of an AV fistula is tion; with time, a cylindrical scar wall is formed by the sub- the high rate of late referrals. Astor et al. (33) reported an cutaneous tissue and the venous wall. impressive relation between timing of referral and the fre- With the rope ladder technique, the technique most fre- quency of the initiation of dialysis treatment with central quently used, progressive dilation is induced along the entire catheters for vascular access. length of the fistula. The worst scenario, i.e., circumscribed There has been much disagreement concerning the time dilation, disruption of wall texture, and formation, is when a fistula is ready for puncture. The DOQI (4) guidelines usually a result of the area puncture technique. Such recommend puncture after 3 to 4 mo. This may be too restric- are a composite of true and false aneurysms, intact parts of the tive. We measured fistula flow and found that there is an wall alternating with scar tissue. Thinning of the wall of the immediate tenfold and more increase of blood flow rate in the vein causes progressive enlargement of the aneurysm, because radial artery, which progressively increases during the first wall stress increases progressively with increasing lumen di- 10 d (7) and tapers off later on. This pattern is in line with the ameter according to the Laplace law. time course established in experimental studies (10). It is therefore the practice of the authors to puncture the fistula no Evaluation of the Patient Before Surgery sooner than 10 d after operation. We do not feel, however, that It is important to instruct the patient in time and to motivate there is a rationale to consistently wait any longer unless there him that forearm are preserved. Puncture of a vein will are specific circumstances such as skin lesions, infection, etc. leave a scar. When a fistula is created, such scars interfere with One decade ago (34), we and others started to use ultra- harmonious dilation and remodeling, cause turbulent flow, and sonography and Duplex sonography as valuable tools for as- predispose to . The veins of both arms, not only of the sessing an established fistula. It has recently been recognized, dominant arm, should remain untouched. For venipuncture, the however, that this technique is also valuable for preoperative veins of the dorsum of the hand should be used as an alterna- assessment (Figure 3) that will provide useful information to the surgeon. The primary aim is the indication to the surgeon whether an anastomosis at the usual site above the wrist will be successful and whether a steal phenomenon is a likely outcome. The lumen of the radial artery and the vein should be measured (Table 1). It is well known (35) that a large propor- tion of the blood flow in the fistula is provided by the ulnar artery via the palmar arch in up to one third of patients. The vasodilatory capacity of the palmar arch should therefore be assessed by calculating the resistance index from post-ischemic diastolic blood flow after fist clenching (Figure 3). This is an index of vascular reactivity to shear stress and of vascular reserve (36). Improvement of fistula outcome by preoperative assessment has been documented by Silva (37). Creation of an AV fistula is an interdisciplinary task. In several countries, the task of coordination is delegated to a “fistula manager” who integrates the activities of the nephrol- ogist, the ultrasonographer, the surgeon, or the interventional radiologist (38). The creation of fistulae should be delegated to a restricted number of dedicated surgeons, because good results are only achieved by surgeons with considerable expertise.

Surgical Technique Figure 2. The three different types of cannulation and their conse- Today, the most frequently used technique of anastomosis is quences dependent on selection of cannulation sites. 1, rope-ladder the (artery) side to (vein) end technique (in the following, the puncture; 2, area puncture; 3, buttonhole puncture. Reprinted with sequence is always artery to vein). Historically, the first anas- permission from reference 32. tomoses used (1) were side-to-side; later on, the end-to-end 1672 Journal of the American Society of Nephrology J Am Soc Nephrol 14: 1669–1680, 2003

Figure 3. Preoperative imaging of the radial artery by color flow duplex sonography. Doppler frequency spectrum shows a high-resis- tance flow with a clenched fist (typical tricyclic flow; left) and a low-resistance flow after release (right; typical low resistance with a RI 0.67 causing high diastolic flow). Maximal systolic flow velocity Ϫ Diastolic flow velocity RI ϭ Maximal systolic flow velocity

technique was introduced, but today the side-to-end technique Figure 4. (Panel A) B-mode sonogram showing a longitudinal section is the most commonly used approach. All three techniques of an arteriovenous fistula created by anastomosing the cephalic vein have advantages and disadvantages. (V) to the radial artery (A) at the wrist in a side-to-end fashion. (Panel Side-to-Side Anastomosis. The advantage of side-to-side B) With the same sectional view, Color Doppler sonography shows anastomosis is its technical simplicity. It is also easy to test turbulent flow at the av anastomosis. The radial artery (A) is feeding the distensibility of the proximal vein from the distal venous the shunt vein (V). limb, particularly before it is ligated after creation of the anastomosis. The disadvantage is a definite risk of venous predispose to ischemia of the hand. The risk is particularly high with swelling of the hand. This can be avoided by ligation of in elderly and diabetic patients. One of the maneuvers to the distal run-off vein, thus achieving a functional side-to-end optimize flow in a fistula is to avoid acute angles when the anastomosis. The risk of venous hypertension in the distal vessels are anastomosed, but when the radial artery is sclerosed venous limb is a particular problem of anastomoses in the acute angles cannot be consistently avoided with the end-to- elbow area. end technique. A final disadvantage is that if venous thrombo- End-to-End Anastomosis. The advantage of end-to-end sis supervenes it will automatically extend into the arterial limb anastomosis is that the fistula flow is limited, thus avoiding a of the fistula. hypercirculatory state. The disadvantage is that the anastomo- Side-to-End Anastomosis (Figure 4). Although several sis is technically more demanding. Problems particularly arise techniques for anastomosis are available, the side-to-end anas- when there are large discrepancies of the luminal diameters tomosis has deservedly become the most commonly used tech- between artery and vein. The most serious problem is, how- nique. It is absolutely indicated when artery and vein are far ever, that ligation of the distal limb of the radial artery may apart and must be brought closely together to create an anas- tomosis. The side-to-end technique will then allow anastomo- sis of the vessels without creating an acute angle. As a further a Table 1. Prediction of poor av-fistule outcome advantage, a venous will affect only the venous limb if it supervenes. If the fistula has to be revised, it is easy • Arterial diameter Ͻ 1.5 mm (internal diameter) to create an anastomosis at a more proximal site. • Venous diameter Ͻ 2.5 mm (using a tourniquet) This type of anastomosis poses a number of technical prob- • Resistance index Ͼ 0.8 (after fist clenching) lems, detailed below, which probably explain the high primary a Preoperative imaging by Color Doppler sonography. malfunction rates reported in some series (39,40,41). J Am Soc Nephrol 14: 1669–1680, 2003 The Arteriovenous Fistula 1673

Technical Points Determining Success luminal narrowing, turbulence, and stenosis. Torque can be An AV fistula transforms a vein into a high-flow vessel. It is relieved if the vein is rotated in an antegrade direction as obvious that obstacles to flow must be avoided, e.g., kinking, illustrated in Figure 6. acute angles, torque etc. They create turbulence, damage en- It is not advisable to ligate run-off veins at the time of first dothelial cells, and increase the risk of stenosis formation. fistula surgery, because it is impossible to predict the future Transverse cutaneous incisions should be avoided, and we function of the fistula. Venous tissue may be extremely useful recommend longitudinal incisions if possible. later on, e.g., for patches, grafts etc. If venous hypertension It has been recommended that veins should be mobilized so develops, veins can then be ligated in a targeted fashion. that they can be more easily adapted to the artery. This ma- An anastomosis at the level of the wrist is only sensible if neuver removes adventitial layer and vasa vasorum, thus pre- both artery and vein are able to dilate (7) so as to accommodate disposing to sclerosis and stenosis. There is no doubt that veins an increase in blood flow by a factor of 20 to 100. Therefore occasionally have to be used for transposition or superficial- the ultrasonographer and later the surgeon must evaluate the ization, but this should not be done at the time of the first quality of the vessels, particularly of the artery. This is increas- surgical intervention, when veins are still thin-walled. During ingly important because of the rising proportion of elderly and a second procedure, when veins have matured and remodeled, they can be used. For this purpose, one can even create a temporary AV anastomosis; not to obtain a fistula for punc- turing, but to create a vein suitable for later transposition or superficialization. Endothelial cell damage from clamping thin-walled veins should be avoided to prevent late stenoses. Digital compression is safe for interruption of blood flow. Instead of forcefully dilating a spastic venous segment, e.g., with a Fogarty catheter, we enter a venous catheter from the distal limb of the veins and gently dilate the vein by injecting warm saline. If this is not sufficient, papavarin and nitroglycerin are administered locally. The length of the arteriotomy must be guided by the angle that will be achieved when adapting the vein to the artery, as illustrated in Figure 5. When mobilizing the vein, one should avoid torque, causing

Figure 6. (Panel A) If a distant vein is mobilized and the venous stump is made to meet the artery without any adaptation, there is a high risk that the vein undergoes torsion, which is often responsible Figure 5. (Panel A) The venous stump is cut in a direction parallel to for early failure and thrombosis. (Panel B) An outward directed the artery. If an acute angle is created between the artery and the vein, rotation of the vein avoids this risk of torsion. Variable rotation the result will be a long arteriotomy, exceeding by far the diameter of between 60 and 120 degrees has to be imposed. The necessary degree both artery and vein. (Panel B) If the vein approaches the artery at an of rotation can be estimated before starting to suture the anastomosis angle of 90 degrees, the length of the anastomosis will equal the by injecting heparinized saline into the proximal stump of the vein diameter of the vein. after it has been compressed with the finger. 1674 Journal of the American Society of Nephrology J Am Soc Nephrol 14: 1669–1680, 2003 diabetic patients with sclerosed or calcified radial arteries. It is substantially below the DOQI target of 25 episodes per 100 of interest that, in contrast to the carotid and coronary arteries, patient-years for AV fistulae. the radial artery rarely develops atherosclerotic plaques. When evaluating the arteries and veins during surgery, it is useful to Perioperative Management do this with the aid of magnification glasses or even a One has three anesthesia options: local anesthesia (infiltra- microscope. tion), regional anesthesia (brachial plexus block), or general At the level of the wrist, the cephalic vein divides into a anesthesia. smaller branch that lies closer to the radial artery and a larger Local anesthesia is simple and commonly well tolerated, but branch running across the dorsum of the hand. The smaller it has the disadvantage of causing local edema thus, increasing branch usually has a valve impeding venous run-off, and the the risk of infection. Furthermore, arterial and venous spasms lumen of the vessel is often unable to accommodate high flow are more common and more severe than with regional or rates. In view of such anatomy, it is often wise to select a more general anesthesia. proximal site for anastomosis. Regional anesthesia by infiltration of the brachial or axillary Selection of the vessels and the site for the anastomosis in plexus has the advantage of significantly reducing the fre- some ways resembles chess; one must always anticipate the quency of vascular spasms. It also allows easy surgery-site next two or three moves and must consider what possibilities change, e.g. from wrist to elbow. The disadvantage is that an remain after the fistula has potentially failed. Ideally, creation experienced anesthesiologist is required. of the fistula should not preclude future corrective surgery. General anesthesia is required when time-consuming oper- In selecting the length of the anastomosis, one must consider ations in more proximal parts of the arm are anticipated or the anticipated blood flow. The higher the site of anastomosis, when patients have severe comorbid conditions (44). the higher the future blood flow for any given area of the We advise against routine perioperative use of antibiotics. In anastomosis, and the smaller should the anastomosis conse- diabetic patients and other patients at high risk of bacterial quently be. We do not recommend anastomoses exceeding 6 infection, however, a single dose of an antibiotic, preferably an mm in length at the level of the brachial artery. aminoglycoside with dose adjustment for renal failure, is ad- The suture technique proposed by Tellis (42) is extremely visable. Perioperative administration of antibiotics is obviously useful and is suitable even for the very small vessels of necessary if an infected fistula or graft is operated upon. children. The suture starts in the center of the back wall of the There is also no need for routine use of platelet inhibitors arteriotomy and venotomy. Suturing is continued passing the (45,46). Adequate surgical techniques are more important than corners with excellent visualization throughout the procedure pharmacologic intervention. When surgical problems cannot as shown in Figure 7. be corrected, however, it may be advisable to administer aspi- When closing the skin, it is important to consider that the rin (47) or, in complex cases, even a combination of aspirin and uremic patient, particularly the diabetic uremic patient, is at clopidogrel (48). There is little evidence that routine screening high risk of infection. We avoid sutures that act as a wick, use of hemostasiologic parameters is of any use before the primary only subcutaneous sutures, and close the skin incision by surgical intervention. If recurrent thrombosis has occurred, adapting the edges with tapes. however, a careful screen for items such as antiphospholipid By using the above strategies, we have managed to achieve antibodies, genetic abnormalities (prothrombin polymorphism, a thrombosis rate of eight episodes per 100 patient-years (43), factor V Leiden mutation, protein C, and protein S deficiency), hyperhomocysteinemia, and antithrombin VIII is indicated. The DOPPS data show that malfunction of the primary fistula is less when calcium channel blockers are used (49). This finding is not unexpected in view of the vasodilatory properties of calcium channel blockers. With respect to long- term fistula function, it is of interest that patients on ACE inhibitors have less delayed fistula closure, at least when PTFE grafts are used (50,51). This observation presumably illustrates that vascular remodeling depends on endothelin and angioten- sin II, respectively (25). It remains controversial whether use of intermittent venous congestion through cuff inflation in the postoperative period yields any benefit for long-term fistula function. A priori, it seems unlikely that an intermittent increase in intravascular pressure (and by implication of wall stress) will affect remod- eling of the vein which is primarily the result of increased shear stress. There is no clear evidence of a beneficial effect on late Figure 7. Illustration of the surgical technique to create a side-to-side outcomes. AV anastomosis according to Tellis (42). This technique is particularly Similarly, the widely recommended practice of hand exer- advantageous when creating artery side-to-vein-end anastomoses. cises, such as squeezing a rubber ball at frequent intervals, J Am Soc Nephrol 14: 1669–1680, 2003 The Arteriovenous Fistula 1675 confers no documented benefit. It will increase venous blood flow is the best predictor of thrombosis. The critical flow rate flow, however, and thus appears to be at least sound on is different in PTFE grafts and in AV fistulae (Table 2). For the physiologic grounds. latter, we found that all fistulae thrombosed in which the flow rate was Ͻ 200 ml/min. This is of course far less than what is Monitoring of the Fistula required for optimal blood flow during dialysis. As a result of Nurses should be trained to recognize fistula problems and low blood flow, dialysis will become ineffective and recircu- to pay attention to a progressive increase of venous inflow lation will occur, but measurements of recirculation are con- pressure and post-puncture bleeding time. Regular “fistula siderably less sensitive to predict fistula malfunction and visits” are advisable, i.e., inspection and physical examination thromboses than direct measurements of fistula flow rates (53). of the fistula every 6 or 8 wk. The main purpose is to detect The time course is more important than the absolute values. development and progression of stenoses in time to prevent Figure 8 shows the typical findings when a stenosis develops. eventual thrombosis, so that one is not forced to surgically A number of indicators and predictors of fistula thrombosis correct an established thrombosis. have been discussed in the literature, such as MCP-1, lipid The pathophysiology underlying stenosis formation is tur- abnormalities, homocysteine, etc., but nothing has emerged bulence of blood flow (Figure 8), which activates platelets and which would be helpful for routine monitoring. endothelial cells. In this context, a particular role has been Several procedures help recognition of critically low blood postulated for platelet-derived growth factor (PDGF) (52). flow rates and impending stenoses at the bedside: The final trigger causing thrombosis is a critical reduction of • (high frequency at the site of stenosis) fistula blood flow. Many studies document that low fistula • Hand elevation test (collapse of the post-stenotic venous segment and persisting congestion of the pre-stenotic segment) • Prolonged bleeding after removal of the needle from the puncture site • Elevated venous inflow pressure during hemodialysis ses- sions, particularly progressively increasing venous inflow pressures during consecutive dialysis sessions Once a critically low fistula flow and stenosis have been documented, one has two alternatives: interventional radiology or corrective surgery. Although this is still controversial, we believe as a rule of thumb that interventional radiology using intraluminal dilation with high pressure exceeding 20 atm (ϭ 2026 kpa) and stenting is sensible in the majority of cases for central stenoses at the level of the axillary vein and above, while most of peripheral stenoses should primarily be addressed by surgical correction. The reason for this recommendation is that the acute post- interventional blood flow rates after dilation are admittedly substantial, but the 1-yr and 2-yr unassisted or assisted patency rates are not impressive, presumably because damage to endo- thelial cells predisposes to recurrence of stenosis and throm- bosis. After this maneuver, primary patency rates of 49% for

Table 2. Critical shunt flow volume in dialysis accessa

Av fistule • Minimum flow rate: 350 to 400 ml/min Ͻ300 ml/min recirculation problems Ͻ200 ml/min clotting problems Figure 8. (Panel A) B mode sonogram showing a longitudinal PTFE graft section of an AV fistula created by connecting a PTFE graft • Minimum flow rate: 800 to 1000 ml/min (PTFE) to a native vein (V). At the site of anastomosis, incipient Ͻ shunt stenosis with myointimal proliferation (arrows) is seen. 600 ml/min clotting problems (Panel B) Turbulent Color Doppler flow signals in the region of an a Estimation of shunt blood flow rate: Qb ϭ TAV ϫ A ϫ 60. anastomotic stenosis (arrows) are seen resulting from endothelial Blood flow (Qb; flow volume in ml/min) is the product of cross- and fibromuscular hyperplasia at the graft (PTFE)/vein (V) anas- sectional area of the vessel (A; cm2) and the time averaged velocity tomosis 18 mo after surgery. (TAV; cm ϫ secϪ1). 1676 Journal of the American Society of Nephrology J Am Soc Nephrol 14: 1669–1680, 2003 salvaged forearm and 9% for salvaged upper arm AV fistulae have been reported (54). The reported 12-mo primary patency rate was only 27%, and the overall patency rate of 51% (55). Our results after surgical intervention are more favorable, and reconstruction of the lumen is usually also curative (56).

Alternative Surgical Approaches An increasingly higher proportion of patients requires ap- proaches other than the classical Cimino fistula at the level of the wrist (1), because an increasing proportion of diabetic and elderly patients are unable to achieve high flow rates for optimal fistula function when the radial artery is used for anastomosis. The solution may be anastomosis at a more proximal level. We compared the primary actuarial fistula patency rate in diabetic and nondiabetic patients (57). In contrast to many reports, we found no difference between diabetic and nondia- betic patients. The explanation is that we had created a primary anastomosis at the level of the elbow in 74% of the diabetic patients compared with 32% in nondiabetic patients. While the high fistula undoubtedly has potential disadvantages and risks, this strategy seems justified, because the life expectancy of the elderly type 2 diabetic patients on dialysis is relatively low (58). A more frequent use of anastomoses at the elbow level with or without transposition of basilic veins has also been recommended by others (59). Figure 9. Transposition of the beginning of the lateral cephalic ante- Many nephrologists are hesitant to use the brachial artery for brachial vein to bridge a hemodynamically relevant stenosis of the primary anastomosis out of fear of provoking hypercirculation cephalic vein cephalad of an aneurysm caused by “area cannulation.” and cardiac decompensation. This risk can be minimized if one Elective revision before the onset of the thrombosis avoided the need adopts the procedure of Gracz (60,61). The principle of this of a synthetic venovenous interposition graft. procedure is to use the perforating vein for anastomosis. It connects the superficial and deep veins in the anticubital re- gion. The perforating vein can dilate and remodel only to a With respect to the surgical alternatives in problematic cases, limited extent, thus interposing a natural throttle between the we also refer to a recent review of Mickley (62). artery and the run-off vein. This limits the maximal blood flow. Using this approach, we have not seen a single case of cardiac Complications of the AV Fistula decompensation from high in a series of more Steal Phenomenon. In recent years, ischemic lesions re- than 600 patients. Because of flow limitation, the risk of a steal sulting from an arterial steal phenomenon have become more phenomenon and peripheral ischemia is reduced as well. In frequent in the population of highly comorbid elderly patients obese patients, the cephalic vein (or even a mobilized basilic with and diabetes mellitus. Concerning the vein) has to be brought up often in a second step into a interventional strategies, it is important to distinguish two subcutaneous position. The first superficial segment of the varieties. First, high-flow steal, i.e., when fistulae with very basilic vein in the region of the elbow is too short in many low resistance “suck-off” blood flow from the palmar arc and patients, providing only a short stretch of the vessel for can- the opposite ulnar artery, thus creating critical ischemia of the nulation. Here again the subcutaneous superficialisation of the fingers. In theory, this type of lesion should be relatively easy basilic vein along the medial aspect of the upper arm can yield to correct by limiting the size of the anastomosis and reducing satisfactory longterm results. It is important to leave the prox- fistula flow (63,64). Because the resistance goes with the 4th imal third of the basilic vein untouched to allow venous drain- power of the radius according to Poiseuille’s law, only drastic age during later surgical corrections, e.g., PTFE bridge grafts, reduction of the fistula’s lumen will be effective. To create an etc. effective yet safe lumen is tricky, however, and poses the risk Today numerous rescue operations are available for steno- of low flow and thrombosis. ses, fistula thrombosis, aneurysms, etc. The type of interven- More difficult, but unfortunately increasing in frequency, is tion should be based on pathophysiologic considerations. We the steal phenomenon in patients with low fistula flow. It is present two examples that illustrate that limited reconstruction, primarily the result of stenosed peripheral arteries so that even if necessary with the use of a short PTFE interposition graft, normal blood flow in the fistula will create critical ischemia in allows preservation of a fistula and avoids fistula abandonment distal vascular beds. Preoperative monitoring helps to predict and a PTFE loop graft installation instead (Figures 9 and 11). the risk of low-flow steal from the limited vasodilation of the J Am Soc Nephrol 14: 1669–1680, 2003 The Arteriovenous Fistula 1677

Figure 10. The DRIL technique (distal revascularization–interval ligation). Diagram of an upper arm brachiocephalic fistula and bra- chial artery bypass with interval brachial artery ligation. In this case, Figure 11. This patient developed two aneurysms and a short stenosis the brachial artery was divided below the origin of the fistula. A distal along the cephalic vein. Elective surgical revision was initiated with end-to-end anastomosis between vein bypass graft and distal brachial partial resection of the venous aneurysm and reconstruction of the artery was performed. Reprinted with permission from reference 70. arterial lumen as well as complete resection of a subtotally throm- bosed venous aneurysm, followed by venovenous end-to-end anasto- mosis and resection of a short stenosis with venovenous end-to-end anastomosis. No central venous catheter was needed because cannu- palmar arc arteries as indicated by abnormally low post-isch- lation was possible along the distal part of the cephalic vein. emic diastolic flow after fist clenching (Table 1, Figure 3). There are only a few therapeutic options. One is to close the Congestive . One advantage of the native fistula and use a central catheter. An alternative procedure has AV fistula is that hypercirculation and congestive heart failure originally been proposed by Schanzer (65) and recently re- from high fistula flow are very rare indeed, in contrast with named DRIL (distal revascularization–interval ligation) (66). what is seen with PTFE grafts (67,68). Hypercirculation ensues The principle is illustrated in Figure 10. The artery distal to the if outflow resistance is too low; in other words, when the anastomosis is ligated so that the fistula no longer sucks blood anastomosis is too wide. This problem is more common with off from peripheral vessels. In a second step, the peripheral PTFE grafts and brachial artery fistulae. The only reliable artery is fed via an interposed segment of saphenous vein or diagnostic measure is to quantitate fistula flow. Banding pro- PTFE graft to raise the perfusion pressure. An unresolved issue cedures, i.e., artificial narrowing of the anastomosis have been is whether for such patients, in analogy to hemodilution in recommended, but the result is very unpredictable. Apart from patients with peripheral arterial disease, moderately low he- the desperate act of ligating the fistula, the best intervention is matocrit values should be aimed at to avoid rouleaux formation to recreate a narrower anastomosis. The results of narrowing and microcirculatory stasis or, conversely, whether high he- are often unsatisfactory for reasons explained above (Pois- matocrit values are beneficial by raising pO2 and tissue oxy- seuille’s law). genation. Calcium channel blockers may be contra-productive Stenosis of Central Veins (Paget Schroetter Syndrome). by increasing the run-off from ischemic tissue into adequately A central venous stenosis may unfortunately be clinically vasodilating parts of the circulation. asymptomatic before creating the vascular access and become 1678 Journal of the American Society of Nephrology J Am Soc Nephrol 14: 1669Ð1680, 2003 symptomatic only when flow is increased. If a critical stenosis References is unable to accommodate increased flow rates, the result will 1. Brescia MJ, Cimino JE, Appel K, Hurwich BJ: Chronic hemo- be swelling of the arm and cyanosis as well as formation of dialysis using venipuncture and a surgically created arterio- collaterals on the chest wall. Central stenoses are usually the venous fistula. N Engl J Med 275: 1089–1092, 1966 result of past subclavian catheters (69,70), but alternative 2. Allon M, Robbin ML: Increasing arteriovenous in hemo- causes have to be considered, e.g., pacemaker cables (71), dialysis patients: Problems and solutions. Int 62: 1109– 1124, 2002 primary thrombosis in patients with antiphospholipid antibod- 3. Pisoni RL, Young EW, Dykstra DM, Greenwood RN, Hecking ies or coagulation disorders, compression by tumors, etc. One E, Gillespie B, Wolfe RA, Goodkin DA, Held PJ: Vascular therapeutic option is to ligate the anastomosis and use the other access use in Europe and the United States: Results from the arm after appropriate imaging to exclude bilateral stenosis. A DOPPS. Kidney Int 61: 305–316, 2002 preferable intervention is to correct the stenosis, either by 4. NKF-DOQI Clinical Practice Guidelines for Vascular Access. dilation with stenting (72,73) or by surgical correction (74). New York, National Kidney Foundation, 1997 The latter intervention involves major surgery, however, and 5. Konner K: Primary vascular access in diabetic patients: An audit. carries a considerable surgical risk. It is therefore the less Nephrol Dial Transplant 15: 1317–1325, 2000 desirable option. 6. Rodrõ«guez JA, Lo«pez J, Montse Cle`ries, Vela E and Renal Registry Committee: Vascular access for haemodialysis — An Aneurysm. Aneurysms of the AV fistula are usually the epidemiological study of the Catalan Renal Registry. Nephrol result of destruction of the vessel wall and replacement by Dial Transpl 14: 1651Ð1657, 1999 biophysically inferior collagenous tissue. Once aneurysms 7. Wedgwood KR, Wiggins PA, Guillou PJ: A prospective study of have formed, the law of Laplace predicts that there is a ten- end-to-side vs. side-to-side arteriovenous fistulas for haemodi- dency to progress spontaneously, because wall stress becomes alysis. Brit J Surg 71: 640Ð642, 1984 greater with increasing diameter of the aneurysm. Aneurysm 8. Corpataux JM, Haesler E, Silacci P, Ris HB, Hayoz D: Low- formation is favored by replacement of the vessel wall by scar pressure environment and remodeling of the forearm vein in tissue after repetitive puncture of the same vessel segment. A Brescia-Cimino haemodialysis access. Nephrol Dial Transplant precondition for formation of an aneurysm is usually a stenosis 17: 1067Ð1062, 2002 9. Girard X, London G, Boutouyrie P, Mourad JJ, Safar M, Laurent and a pre-stenotic rise of outflow pressure. Major complica- S: Remodeling of the radial artery in response to a chronic tions are rupture, infection (which is favored by intra-aneurys- increase in shear stress. Hypertension 27: 799Ð803, 1996 matic thrombi), and in rare cases orthograde or retrograde 10. Lehoux ST, Tronc F, Tedgui A: Mechanisms of blood flow- . Before intervention, adequate imaging using ultra- induced vascular enlargement. Biorheology 39: 319Ð324, 2002 sonography is absolutely indispensable for identification of 11. Kamiya A, Togawa T: Adaptive regulation of wall shear stress to thrombi, assessment of the degree of outflow stenosis, and flow change in the canine and carotid artery. Am J Physiol 239: evaluation of the surrounding tissue. The surgical correction H14ÐH21, 1980 includes partial or complete resection of the aneurysmatic sac, 12. Zarins CK, Zatina MA, Giddens DP, Ku DN, Glagov S: Shear correction of accompanying stenoses, and reconstruction of an stress regulation of artery lumen diameter in experimental atherogenesis. J Vasc Surg 5: 413Ð420, 1987 adequate lumen as illustrated in Figure 11. 13. Ballermann BJ, Dardik A, Eng E, Liu A: Shear stress and the endothelium. Kidney Int 54: 100Ð108, 1998 14. Tohda K, Masuda H, Kawamura K, Shozawa T: Differences in Conclusion dilatation between endothelium-preserved and desquamated seg- It is the intention of this brief review to point out that the ments in the flow-loaded rat common carotid artery. Arterioscler biology of the AV fistula is fascinating and that adequate Thromb 12: 519Ð528, 1992 management of the fistula and its complications should be 15. Miller VM, Burnett JCJ: Modulation of NO and endothelin by based on pathophysiologic reasoning. There is no single stan- chronic incrases in blood flow in canine femoral arteries. Am J dard approach, and surgical management must be individual- Physiol 263: H103ÐH108, 1992 16. Ben Driss A, Benessiano J, Poitevin P, Levy BI, Michel JB: ized. One key to success is early referral and early establish- Arterial expansive remodeling induced by high flow rates. Am J ment of a vascular access after preoperative assessment using Physiol 272: H851ÐH858, 1997 ultrasonography. Regular monitoring of the fistula is indicated, 17. Tronc F, Wassef M, Esposito B, Henrion D, Glagov S, Tedgui A: and fistula flow should be assessed in critical cases as the Role of NO in flow-induced remodeling of the rabbit common single most important predictor of fistula thrombosis. It must carotid artery. Arterioscler Thromb Vasc Biol 16: 1256Ð1262, be the aim to prevent thrombosis rather than to intervene on 1996 established thrombosis. 18. Jones GT, Stehbens WE: The ultrastructure of arteries proximal Our personal experience as well as several registry reports to chronic experimental carotid-jugular fistulae in rabbits. Pa- document that native AV fistulae can be established in more thology 27: 36Ð42, 1995 19. Jones GT, Stehbens WE, Martin BJ: Ultrastructural changes in than 80% of the patients. The results are superior to those of arteries proximal to short-term experimental carotid-jugular ar- PTFE grafts. We are aware that there are powerful disincen- teriovenous fistulae in rabbits. Int J Exp Pathol 75: 225Ð232, tives against the AV fistulae, but we hope that nephrologists 1994 can be motivated to try a native AV fistula in all dialysis 20. Tronc F, Mallat Z, Lehoux S, Wassef M, Esposito B, Tedgui A: patients. Role of matrix metalloproteinases in blood flow-induced arterial J Am Soc Nephrol 14: 1669Ð1680, 2003 The Arteriovenous Fistula 1679

enlargement. Arterioscler Thromb Vasc Biol 20: e120Ðe126, 38. Ravani P, Marcelli D, Malbert F: Vascular access surgery man- 2000 aged by renal physicans: The choice of native arteriovenous 21. Abruzzese TA, Guzman RJ, Martin RL, Yee C, Zarins CK, fistulas of hemodialysis. Am J Kidney Dis 40: 1264Ð1276, 2002 Dalman RL: Matrix metalloproteinase inhibition limits arterial 39. Oliver MJ, McCann RL, Indridason OS, Butterly DW, Schwab enlargements in a rodent arteriovenous fistula model. Surgery SJ: Comparison of transposed brachiobasilic fistulas to upper 124: 328Ð334, 1998 arm grafts and brachiocephalic fistulas. Kidney Int 60: 1532Ð 22. Ketteler M, Ritz E: Renal failure: A state of nitric oxide defi- 1539, 2001 ciency. Kidney Int 58: 1356Ð1357, 2000 40. Dixon BS, Novak L, Fangman J: Hemodialysis vascular access 23. Serradell M, Diaz-Ricart M, Cases A, Zurbano MJ, Lopez-Pedret survival: Upper-arm native arteriovenous fistula. Am J Kidney J, Arranz O, Ordinas A, Escolar G: Uremic medium causes Dis 39: 92Ð101, 2002 expression, redistribution and shedding of adhesion molecules in 41. Konner K: The anastomosis of the arteriovenous fistula — Com- cultured endothelial cells. Haematologica 87: 1053Ð1061, 2002 mon errors and their avoidance. Nephrol Dial Transpl 17: 376Ð 24. Serradell M, Diaz-Ricart M, Cases A, Zurbano MJ, Arnar-Salatti 379, 2002 J, Lopez-Pedret J, Ordinas A, Escolar G: Uremic medium dis- 42. Tellis VA, Veith FJ, Sobermann RJ, Freed SZ, Gliedman ML: turbs the hemostatic balance of cultured human endothelial cells. Internal arteriovenous fistula for hemodialysis. Surg Gynecol Thromb Haemost 86: 1099Ð1105, 2001 Obstet 132: 866Ð870, 1971 25. Amann K, Miltenberger-Miltenyi G, Simonaviciene A, Koch A, 43. Konner K, Hulbert-Shearon TE, Roys EC, Port FK: Tailoring the Orth ST, Ritz E: Remodeling of resistance ateries in renal failure: initial vascular access for dialysis patients. Kidney Int 62: 329Ð Effect of endothelin receptor blockade. J Am Soc Nephrol 12: 338, 2002 2040Ð2050, 2001 44. Hovagim AR, Poppers PJ: Anesthesia for vascular access and 26. Vlodaver Z, Edwards JE: Pathologic changes in aortic-coronary peritoneal access for dialysis. In: Vascular and Peritoneal Access arterial saphenous vein grafts. Circulation 44: 719Ð728, 1971 for Dialysis. edited by Andreucci VE, Boston-Dordrecht-Lon- 27. Verma S, Li SH, Badiwala MV, Weisel RD, Fedak PW, Li RK, don, Kluwer Academic Publishers, 1989 Dhillon B, Mickle DA: Endothelin antagonism and interleukin-6 45. Smits JHM, van der Linden J, Blankestijn PJ, Rabelink TJ: inhibition attenuate the proatherogenic effects of C-reactive pro- Coagulation and haemodialysis access thrombosis. Nephrol Dial tein. Circulation 105: 1890Ð1896, 2002 Transpl 15: 1755Ð1760, 2000 28. Ferns GAA, Raines EW, Sprougel KH: Inhibition of neointimal 46. Kaufman JS: Antithrombotic agents and the prevention of access smooth muscle accumulation after angioplasty by an antibody to thrombosis. Semin Dial 13: 40Ð46, 2000 PDGF. Science 253: 1129Ð1132, 1991 47. Andrassy K, Malluche H, Bornefeld H, Comberg M, Ritz E, 29. Kalinowski L, Matys T Chabielska E, Buczko W, Malinski T: Jesdinski H, Mo¬hring K: Prevention of p.o. clotting of a.v. Angiotensin II AT1 receptor antagonists inhibit platelet adhesion Cimino fistulae with acethylsalicyl acid. Klin Wschr 52: 348Ð and aggregation by nitric oxide release. Hypertension 40: 521Ð 349, 1974 527, 2002 48. Mysliwiec M: Vascular access thrombosis — What are the 30. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, possibilities of intervention ? Nephrol Dial Transplant 12: 876Ð McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, 878, 1997 Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM: 49. Saran R, Dykstra DM, Wolfe RA, Gillespie B, Held PJ, Young Endothelial cells in physiology and in the pathophysiology of EW: Association between vascular access failure and the use of vascular disorders. Blood 91: 3527Ð3561, 1998 specific drugs: the Dialysis Outcomes and Practice Pattern Study 31. Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, (DOPPS). Am J Kidney Dis 40: 1255Ð1263, 2002 Bieglmayer C, Endler G, Muellner C, Speiser W, Wagner O: 50. Gradzki R, Dhingra RK, Port FK, Roys E, Weitzel WF, Messana Leptin induces endothelin-1 in endothelial cells in vitro. Circ Res JM: Use of ACE inhibitors associated with prolonged survival of 90: 711Ð718, 2002 arteriovenous grafts. Am J Kidney Dis 38: 1240Ð1244, 2001 32. Kro¬nung G: Plastic deformation of Cimino fistula by repeated 51. Saran R, Dykstra DM, Wolfe RA, Gillespie B, Held PJ, Young puncture. Dial Transplant 13: 635Ð638, 1984 EW; Dialysis Outcomes and Practice Pattern Study (DOPPS): 33. Astor BC, Eustace JA, Powe NR, Klag MJ, Sadler JH, Fink NE, Association between vascular access failure and the use of spe- Coresh J for the CHOICE Study: Timing of nephrologist referral cific drugs: The Dialysis Outcome and Practice Patterns Study and arteriovenous access use: The CHOICE study. Am J Kidney (DOPPS). Am J Kidney Dis 40: 1255Ð1263, 2002 Dis 38: 494Ð501, 2001 52. De Marchi S, Falleti E, Giacomello R, Stel G, Cecchin E, 34. Nonnast-Daniel B, Martin RP, Lindert O, Mu¬gge A, Schaefer J, Sepiacci G, Bortolotti N, Zanello F, Gonano F, Bartoli E: Risk Lieth Hvd, So¬chtig E, Galanski M, Koch K-M, Daniel WG: factors for vascular disease and arteriovenous fistula dysfunction Colour doppler ultrasound assessment of arteriovenous haemo- in hemodialysis patients. J Am Soc Nephrol 7: 1169Ð1177, 1996 dialysis fistulas. Lancet 339: 143Ð145, 1992 53. Tonelli M, Hirsch D, Clark TWI, Wile C, Mossop P, Marryatt J, 35. Sivanesan S, How TV, Bakran A: Characterizing flow distribu- Jindal K: Access flow monitoring of patients with native vessel tions in AV fistulae for haemodialysis access. Nephrol Dial arteriovenous fistulae and previous angioplasty. J Am Soc Neph- Transplant 13: 3108Ð3110, 1998 rol 13: 2969Ð2973, 2002 36. Malovrh M: Native arteriovenous fistula: Preoperative evalua- 54. Turmel-Rodrigues L, Pengloan J, Rodrige H, Brillet G, Lataste tion. Am J Kidney Dis 39: 1218Ð1225, 2002 A, Pierre D, Jourdan J-L, Blanchard D: Treatment of failed 37. Silva MB Jr, Simonian GT, Hobson RW II: Increasing use of native arteriovenous fistulae for hemodialysis by interventional autogenous fistulas: selection of dialysis sites by Duplex scan- radiology. Kidney Int 57: 1124Ð1140, 2000 ning and transposition of forearm veins. Semin Vasc Surg 13: 55. Haage P, Vorwerk D, Wildberger JE, Piroth W, Schu¬rmann K, 44Ð48, 2000 Guenther RW: Percutaneous treatment of thrombosed primary 1680 Journal of the American Society of Nephrology J Am Soc Nephrol 14: 1669Ð1680, 2003

arteriovenous hemodialysis access fistulae. Kidney Int 57: 1169Ð 66. Knox RC, Berman SS, Hughes JD, Gentile AT, Mills JL: Distal 1175, 2000 revascularization-interval ligation: A durable and effective treat- 56. Konner K: Interventional strategies for hemodialysis fistulae and ment for ischemic steal syndrome after hemodialysis access. grafts: Interventional radiology or surgery. Nephrol Dial Trans- J Vasc Surg 36: 250Ð256, 2002 plant 15: 1922Ð1923, 2000 67. O‘Regan S, Lemaitre P, Kaye M: Hemodynamic studies in 57. Konner K: Primary vascular access in diabetic patients: An audit. patients with expanded polytetrafluoroethylene (PTFE) forearm Nephrol Dial Transplant 15: 1317Ð1325, 2000 grafts. Clin Nephrol 10: 96Ð100, 1978 58. Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes 68. Dikow R, Schwenger V, Zeier M, Ritz E: Do AV fistulas mellitus. N Engl J Med 341: 1127Ð1133, 1999 contribute to cardiac mortality in hemodialysis patients? Semin 59. Hakaim AG, Nalbandian M, Scott T: Superior maturation and Dial 15: 14Ð17, 2002 patency of primary brachiocephalic and transposed basilic arte- 69. Schwab SJ, Quarles LD, Middleton JP, Cohan RH, Saeed M, riovenous fistulae in patients with diabetes. J Vasc Surg 27: Dennis VW: Hemodialysis-associated subclavian vein stenosis. 154Ð157, 1998 Kidney Int 33: 1156Ð1159, 1988 60. Gracz KC, Ing TS, Soung LS, Armbruster KFE, Seim SK, 70. Schillinger F, Schillinger D, Montagnac R, Milcent T: Post Merfkel FK: Proximal forearm fistula for maintenance hemodi- catheterization vein stenosis in haemodialysis: Comparative an- alysis. Kidney Int 11: 71Ð74, 1977 giographic study of 50 subclavian and 50 internal jugular ac- 61. Bender MHM, Bruyninckx CMA, Gerlag PGGG: The brachio- cesses. Nephrol Dial Transpl 6: 722Ð724, 1991 cephalic elbow fistula: A useful alternative angioaccess for per- 71. Konner K, Vorwerk D: Permanent pacemaker wires causing manent hemodialysis. J Vasc Surg 20: 808Ð813, 1994 subclavian vein stenosis in presence of AV fistula — Is it ever 62. Mickley V: Surgical alternatives to central venous catheters in chronic renal replacement therapy. Nephrol Dial Transplant wrong to try angioplasty and stenting ? Nephrol Dial Transplant 2003, in press 12: 1735Ð1738, 1997 63. Burrows L, Kwun K, Schanzer H, Haimov M: Haemodynamic 72. Kovalik EC, Newman GE, Suhocki P, Knelson M, Schwab SJ: dangers of high flow arteriovenous fistulas. Proc Eur Dial Trans- Correction of central venous stenoses: Use of angioplasty and plant Assoc 16: 686Ð687, 1979 vascular Wallstents. Kidney Int 45: 1177Ð1181, 1994 64. Kinnaert P, Struyven J, Mathieu J, Vereerstaeten P, Toussaint C, 73. Vorwerk D, Guenther RW, Mann H, Bohndorf K, Keulers P, van Gerrstruyden J: Intermittent of the hand after Alzen G, Sohn M, Kistler D: Venous stenosis and occlusion in creation of an arteriovenous fistula in the forearm. Am J Surg hemodialysis shunts: Follow-up results of stent placement in 65 139: 838Ð843, 1980 patients. Radiology 195: 140Ð146, 1995 65. Schanzer H, Schwartz M, Harrington E, Haimov M: Treatment of 74. Duncan JM, Baldwin RT, Caralis JP, Cooley DA: Subclavian ischaemia due to “steal” by arteriovenous fistula with distal artery vein-to-right atrial bypass for symptomatic venous hypertension. ligation and revascularization. J Vasc Surg 7: 770Ð773, 1988 Ann Thorac Surg 52: 1342Ð1343, 1991

Access to UpToDate on-line is available for additional clinical information at http://www.jasn.org/