Access Ligation in Transplant Patients

Abstract

Access surgeons will encounter patients with functioning transplants who want to lose their fistula, and every dialysis unit sees patients returning after a failed kidney transplant for whom an old fistula is a readily available lifeline. The decision is straightforward in patients with perfectly functioning transplants and disabling complications of their fistula, or in patients with failing transplants and a good fistula. The challenge is to make this decision in patients with good transplant function and an asymptomatic fistula. Despite improvements in one-year survival of renal grafts, the long-term graft survival has improved modestly. This means about half of the patients with a successful kidney transplant will return to dialysis within 10 years. Use of recently developed risk calculators, based on clinical parameters, may help in the decision process. A high flow fistula can lead to heart failure but most fistulae are well tolerated in asymptomatic patients and the effects of closure of the AVF on the heart are modest. Recent evidence suggests that there may be benefits of a functioning AVF that may need to be considered in this decision process. This article reviews the literature and comes to pragmatic recommendations of what to do with this conundrum.

Keywords

Access ligation Arteriovenous fistula Renal transplant

Introduction

A good arteriovenous fistula (AVF) is a lifeline for dialysis patients. This lifeline is redundant in patients who receive renal replacement therapy through a functioning kidney transplant. However, transplants can fail and a mature fistula can be a readily available safety net in cases of transplant failure. An AVF is an intentionally created abnormal physiological situation in order to facilitate dialysis. A fistula could therefore have negative consequences for a patient even if well tolerated. Every access surgeon will encounter patients with functioning transplants who want to lose their fistula and every dialysis unit sees patients returning after a failed kidney transplant. To ligate or not to ligate that is the question. The decision to ligate an AVF is straightforward in patients with a perfectly functioning transplant who present with disabling complications of their fistula. Similarly, the decision is clear-cut in patients with a failing transplant and a good fistula. The challenge is to make this decision in a patient with a good transplant kidney function and an asymptomatic fistula. In those cases the decision revolves around a deliberation of the estimated probability of future transplant failure versus the probability of future harm due to a well-functioning fistula. This review aims to aid decision making in this conundrum.

Personal Experience

In 15 years, from January 2000 till December 2015, 408 dialysis patients from our unit received a renal transplant. In 43 cases (10.5%) the patient returned to hemodialysis due to transplant failure: in 23 cases (57%) dialysis was commenced with a fistula and in 20 cases (43%) with a central venous catheter. Twenty patients started on an old AVF and in three cases a new AVF was created. The median delay from transplant to restarting dialysis after a failed transplant was 14 months. Sixty percent of patients with a failed transplant restarted dialysis by 1.5 years post-transplant (Fig. 1).

Fig. 1

Cumulative probability graph of return to dialysis due to kidney transplant failure of those with failed transplants by time in months.

Transplant Survival

Despite the significant improvements in one-year survival of renal grafts over the last decade, the medium and long-term graft survivals have improved only modestly. The current death-censored graft failure rates at 5 and 10 years are around 25% and 50%, respectively, for deceased donor kidney transplants, with slightly better survival for living donor transplants (1). This means about one-fourth of the patients with a successful kidney transplant will return to dialysis within 5 years and about half within 10 years. It is, therefore, important to keep this in mind when faced with a patient requesting ligation of a functioning AVF. An Italian study, of 542 renal transplant patients over 10 years, found that 91 (17%) patients had restarted dialysis: 89 patients on hemodialysis and two patients on continuous ambulatory peritoneal dialysis (CAPD). Of the 365 patients with functioning kidney transplants, 198 patients had a patent fistula, while 167 AVFs had closed. One hundred and twenty-five patients had a spontaneous closure and 42 patients had a surgical closure. Of the 89 patients put back on dialysis, 49 patients used the previous AVF, while a new AVF had to be created in 40 patients. In nine of these patients a previous AVF had been ligated. In all these patients the AVF was ligated due to local problems (2).

Factors Affecting Kidney Transplant Survival

A number of factors are known to affect long-term survival of the kidney graft. These can be divided into alloantigen-dependent and non-alloantigen-dependent factors. The alloantigen-dependent factors are delayed graft function, human leukocyte antigen (HLA) mismatching, cold ischemia time, the development of anti-HLA antibodies, and inadequate immunosuppressive therapy. The non-alloantigen factors implicated in late graft failure are inadequate renal mass, prior and ongoing tissue injury, non-compliance, post-transplant hypertension, hyperlipidemia, more marginal kidneys, calcineurin toxicity, cytomegalovirus (CMV) seropositivity, and recurrent or de novo glomerular disease (3). Presence of a combination of these factors in a given patient may suggest that the patient is more likely to return to dialysis in the future.

Prediction of Transplant Survival

A number of prediction tools for kidney transplant survival have been developed. Some of these are based on protocol biopsies (4). The usefulness of protocol biopsies is debated because of risk, cost, and long-term benefits (5–7). A number of predictive bio-markers have been developed but their widespread use is limited by the requirement for specialized laboratory tests (8–11). Therefore, most clinicians currently base their prediction of future kidney transplant function on serial serum creatinine or serial estimated glomerular filtration rate (eGFR) measurements, following stabilization of graft function after transplantation.

Two recently developed prediction tools based on clinical parameters look promising. The first one based on the United States Renal Data System (USRDS) data includes the recipient's age, race, MDRD GFR at 1 year, hospitalization in first 1 year, primary cause of chronic kidney disease (CKD) and primary insurance in the abbreviated model. This model is developed to predict graft failure 5 years’ post-transplantation (12). The other risk calculator is based on recipient age, sex, race, acute rejection, eGFR, serum albumin level, and urine albumin creatinine ratio at 1 year post-transplant. This has been developed in a cohort from Birmingham, UK, and validated in three independent cohorts from Leeds (UK), Tours in France and Halifax in Canada. This model also predicts risk of graft failure 5 years’ post-transplantation and has been shown to result in 30% improvement in reclassification of transplant failure compared with the USRDS-based model (13). A user-friendly online risk predictor is available at http://www.renalmed.co.uk/risk-calculator. Use of this risk calculator may help in the decision process and demonstrate to the patient the probable risk of graft failure in a numerical form and facilitate the discussion in regards to advisability of fistula ligation.

Local Problems of AVF

The natural history of a well-functioning AVF is dilatation of the feeding artery and draining veins leading to increasing flow through the fistula. This has both systemic and local effects. Systemic effects mainly revolve around the systemic circulatory overload of a high flow AVF. Local complications of AVF include thrombosis, infections, aneurysm formations and distal limb ischemia.

Local complications of AVF include infections, bleeding, distal ischemia, aneurysm formation, venous hypertension and thrombosis. Infections are rare in AVF that are not used. Similarly, AVF thrombosis is not an issue in patients with a functioning transplant. Venous hypertension, as a result of an outflow stenosis, often leads to fistula thrombosis but may require fistula ligation. Aneurysm formation is the main reason why patients want their AVF ligated. The most common variety of AVF aneurysm is the camel hump type, which is associated with repeated cannulation trauma (14). AVF aneurysms are less common in AVF that are not used (14). Aneurysms in non-used AVFs are more likely the juxta-anastomotic type and the generalized venous dilatation, the hose-pipe variety type (14). These aneurysms are more common in upper-arm AVFs, and are associated with high flow states. Similarly, distal ischemia is much more common in upper-arm AVFs than in forearm AVFs (15). In conclusion, local problems leading to requests for AVF ligation are more likely in upper-arm AVFs than in forearm AVFs.

Systemic Problems of AVF

The effects of AV access creation on the cardiovascular system are well known. The cardiac output increases by 10% to 20% as a result of a drop in systemic peripheral resistance (16, 17) and increased preload (18). This leads to cardiac changes such as left ventricular remodeling, which may be harmful (19). Heart failure is very common in dialysis patients and has serious consequences for the patient (20–22). However, a large US study found that AVF use had no significant association with the incidence of heart failure (HF) or acute coronary syndrome (23). Similarly, an AVF has no significant effect on the development of pulmonary hypertension (24, 25).

On the other hand, kidney transplantation decreases cardiovascular mortality and prevalence of HF (26). Despite this, HF and cardiac hypertrophy are still important concerns after transplantation. Kidney transplantation does not reduce left ventricular hypertrophy (LVH) (27). Some studies suggest a significant contribution of a patent AVF to residual LVH (28–30).

Benefits of a Functioning AVF

There are potential beneficial effects of a functioning AVF that may need to be considered in the decision-making process and in the discussion with the patient.

Effect on blood pressure (BP): an AVF adds a low resistance, high-compliance system to the high pressure arterial system resulting in lower peripheral resistance and a reduction in BP (31). Successful AVF has been shown to reduce BP in patients with end-stage kidney disease (16). Recently, implantation of an arteriovenous coupler (in effect an AVF) between the iliac artery and vein, has been shown in a randomized controlled study to lower 24-hour ambulatory systolic BP by about 15 mmHg on average in patients with treatment-resistant hypertension (32). This technique is promising for treatment-resistant hypertension in the future (31). Conversely, closure of AVF in kidney transplant patients has been shown to increase office diastolic BP and 24-hour diastolic BP (29, 30, 33). It is advisable to monitor BP closely in patients who undergo fistula ligation.

Effect on arterial stiffness: creation of an AVF in patients with end-stage kidney disease has been shown to reduce arterial stiffness in addition to BP, and increase left ventricular ejection fraction (16). The association between increased arterial stiffness and cardiovascular events is well established in both CKD and non-CKD patients.

Effect on renal function decline: Recently, AVF has been shown to be associated with reduction in the rate of decline of glomerular filtration rate (GFR) in patients with advanced CKD. Although the exact mechanism is unknown, it is possible that the physiological effects of AVF, such as local and remote changes in the micro-circulation, increased stroke volume and ejection fraction, reduction in BP, improved endothelial function, reduction in arterial stiffness, may play a role (34, 35). This cannot directly be extrapolated to patients with a functioning kidney transplant and AVF, but one could hypothesize that a functioning AVF may have a beneficial role in preserving late kidney graft function.

Effects of AVF Closure

The effects of AVF closure on the AVF-induced structural changes in the heart are hotly debated. Multiple case reports in symptomatic patients have described a reduction of signs of HF and dramatic reduction of symptoms following AVF closure (36–39). The effects of AVF closure are less clear in asymptomatic patients. Several studies found that closure of a high-flow AVF induces long-term regression of LVH (28, 30). One study found that the change in LVH after AVF closure was related to the preoperative left ventricular dimensions but not to fistula flow (28). Some authors feel that residual concentric remodeling as well as diastolic blood pressure increases may blunt the expected beneficial cardiac effects of the AVF closure (30, 33). In contrast, another study found that AVF closure was associated with decrease in both eccentric and concentric hypertrophy and showed a trend towards normalization of the cardiac structure (40).

A recent study from Glasgow, UK, found that temporary occlusion with digital pressure of an AVF, just proximal to the arteriovenous anastomosis, leads to reduced cardiac output and improved oxygen delivery. This difference is most marked in patients with high-flow AVF (>2000 mL/min). The authors concluded that high-flow AVF may lead to high cardiac output state, which is reversible on occlusion of the AVF (41). However, the actual reductions in cardiac output were fairly modest and on average less than 1 L/min. Furthermore, the long-term effects of AVF closure in asymptomatic patients remain unknown.

Functioning AVFs are well tolerated in most renal transplant patients. Patard et al observed that in 160 renal transplant patients with AVF only four patients had to undergo surgical closure of their AVF for high vascular flow. The authors concluded that since most patients’ fistulae were still functional and well tolerated at long-term follow-up, systematic closure of an AVF after renal transplant does not appear to be necessary (42).

A Brazilian study compared 39 asymptomatic kidney transplant recipients with functioning AVFs and 22 asymptomatic kidney transplant recipients who had their AVF closed 2 months after transplant for esthetic reasons only. All had a stable graft function. After an average follow-up of 14 months, only the left ventricular (LV) end-diastolic dimension was reduced in the AVF closure group. All other LV parameters: LV mass index, LV posterior wall thickness, interventricular septum, ejection fraction, cardiac index and the calculated systemic vascular resistance did not differ significantly between groups. LVH was found in 95% of the patients in open AVF group and in 91% of the patients without an AVF (43). The authors concluded that the persistence of mature AV fistulae for prolonged periods of time had little impact on cardiac morphology and function of stable renal transplant patients with adequate renal function. They do not support routine closure of these fistulae in all renal transplant patients (43). A Belgian study followed 41 renal transplant patients after an AVF was closed about 2 years post-transplantation. After an average follow-up of 4 years, three patients returned to dialysis because of transplant failure. A new AVF could be created in all three patients who needed to resume hemodialysis (44). This suggests that ligation of an AVF may not be an unmitigated disaster. However, the low incidence of renal graft loss is likely to increase with a longer follow-up. Arguments against AVF closure are provided by the Brazilian study, which found limited cardiac effects of AVF closure in asymptomatic patients (43) and the French study, which did not find significant morbidity of functioning AVFs in asymptomatic transplant patients (42). Arteriovenous access blood flow is different between the anatomical locations of AVF with flow generally higher in upper-arm AVF (45). Forearm AVFs are less often associated with high flow, have a lower probability of local complications (41), but have better long-term cumulative patency (46).

Conclusions

Based on the discussion above, we suggest the following guidelines regarding AVF closure post-transplant.

An asymptomatic AVF should not be ligated.

Do not ligate the vascular access within one year of renal transplantation unless the patient has significant symptoms, such as severe venous hypertension, risk of rupture from pseudoaneurysms, significant high output cardiac failure, or distal ischemia

Assess the risk of graft failure using the clinical risk calculators mentioned above. Only consider ligation of the AVF in cases of a stable transplant function after consultation with the nephrologist.

Avoid ligating a forearm AVF, as they are associated with lower flows, fewer local complications, have fewer systemic sequelae, but have better long-term AVF patency.

Footnotes

Financial support: No grants or funding have been received for this study.

Conflict of interest: None of the authors has financial interest related to this study to disclose.

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