Optimal timing for vascular access creation

Abstract

Many guidelines recommend that end-stage renal disease (ESRD) patients should have a permanent vascular access, preferably an autologous arteriovenous fistula (AVF), at the start of renal replacement therapy. Nevertheless, a large proportion of patients still start hemodialysis with a central venous catheter (CVC). On the other hand, there are increasing numbers of patients in whom an AVF has been created, but who never actually end up on dialysis, as well as a substantial number of patients in whom creation of a vascular access has been attempted unsuccessfully.

To improve this situation, timely exploration to assess suitability for and creation of preemptive AVF should be promoted. Decision to construct an AVF should depend on the likelihood and rate of progression to ESRD. For this goal, some reliable prediction models are available. Also, the likelihood that such an attempt will result in a successful outcome should be taken into account, but suitable validated models to accurately make such estimates are lacking. Next to patient-specific factors, some local conditions such as easy access to a vascular surgeon should also be incorporated in the decision-making process between the nephrology team and the patient.

Keywords

Arteriovenous fistula Chronic kidney disease progression Hemodialysis initiation Timing of creation Vascular access

Introduction

Clinical practice guidelines strongly recommend the autologous arteriovenous ﬁstula (AVF) as the preferred vascular access in all eligible chronic kidney disease (CKD) patients, as it is associated with better outcomes and improved quality of life (1), and reduces costs as compared to arteriovenous grafts (AVG) and central venous catheters (CVCs) (2). Therefore, in the ideal world, all patients starting hemodialysis (HD) would have a well-functioning AVF that can be successfully used from the first dialysis onwards. Such an ideal scenario has many advantages, as it avoids the need for a temporary CVC. Use of a CVC is associated with a higher risk for infections, cardiovascular events and even mortality (1, 3). Placement of both subclavian and jugular CVC can induce stenosis of the central veins, jeopardizing the later creation of an autologous vascular access on that side (4). In addition, CVCs are uncomfortable for the patient and induce additional hospitalization costs.

Many decisions around vascular access should be based on a shared decision-making process, involving both clinician and patient. However, information on patients’ experiences in this regard is rather scant. In a European survey exploring views on which vascular access-related decisions deserved priority for research and guidance, timing of vascular access creation was ranked as the 7^th item by nephrologists, whereas it was only labelled as item 26 by patients, and selection of vascular access type was placed as second most important topic by both (5).

The high prevalence of morbidity and mortality in the CKD population, with cardiovascular disease ranking amongst the most important (6, 7) means that the creation of a vascular access can be cumbersome, or result in suffering of the patient and much investment of time and energy without any useful outcome. In addition, it has been reported that an increasing number of patients (especially the elderly) have received creation of an AVF that was never used, either because they did not progress to need dialysis, or because they died of a non-nephrology-related causes before that time (8, 9).

In this paper, we will shortly review aspects of patient selection for and timing of pre-emptive creation of autologous vascular access. To achieve this goal, we will need tools to identify patients in whom creation of AVF is deemed (un)suitable, and to estimate rate of progression to end-stage renal disease (ESRD), and survival.

Starting dialysis with or without an AVF

This study was based on systematic literature search and did not identify any randomized controlled trials (RCTs) on this topic.

Recent published data from Dialysis Outcomes and Practice Patterns Study (DOPPS 5) (2012-2014) showed a high percentage of CVC and a low percentage of AVF use (67% and 28%, respectively) in patients starting HD in the USA, although this was already an improvement as compared to earlier data (10). The situation seems better in most European countries and in Japan (50%-60% and 84% AVF use, respectively). Preemptive AVF placement in patients seen by a nephrology service more than 4 months before start of HD was between 71% and 81% in UK, Japan, Germany, Italy and Sweden compared to only 55% in USA (10). This highlights that late referral to a nephrology service and local practice patterns can influence the percentage of patients with autologous AVF at start of dialysis. In the CHOICE study, initiating HD with a non-tunneled CVC was associated with more severe comorbidity and late referral (11). In another study, late referral to a vascular surgery service and primary access failure were identified as factors contributing to a low incidence of patients starting dialysis with a functioning AVF (12). Data from the DOPPS 4 study confirmed that probability to start HD with permanent vascular access versus non-tunneled CVC is lower as the period between referral and first evaluation by a vascular surgery program, as well as the time between first evaluation and actual vascular access placement, is prolonged (13).

Also, in patients who started HD using a non-tunneled CVC, early conversion from CVC to AVF is associated with reduced hospitalization risk (14) and improved survival (15). However, 90 days after HD initiation, still 59.4% of patients are dialyzed by a CVC. Female gender, black race, older age and cardiovascular comorbidity are factors associated with higher probability of CVC use (11). In a large retrospective cohort study in 11,290 patients (mean age 70 years and median estimated GFR [eGFR] 17.7 mL/min/1.73 m²) 25% of patients initiated HD in the first year but only 39% of those had a permanent access at HD start, a number decreasing with age (8). At the same time, the percentage of patients who did not start renal replacement therapy (RRT) increased with age. Taken together, to increase the low rates of permanent access placement, more unnecessary procedures would have to be performed, especially in the older population. The authors concluded “If all patients had been referred for permanent access surgery at cohort entry, the ratio of unnecessary to necessary procedures after 2 years of follow-up would have been 5 to 1 for patients aged 85-100 years versus only 0.5 to 1 for those aged 18-44 years” (8).

Oliver et al (16) followed 1929 pre-dialysis patients who underwent pre-emptive AVF placement. During a period of at least 2 years, 81% of patients initiated HD, 9% of patients died and 10% remained on pre-dialysis. In this study, the probability of starting RRT was significantly modified by age, sex and comorbidity, where younger males and those with more comorbidities had a higher risk to start HD than their older, female and healthier counterparts (16). In addition, some recent data suggest an association between pre-emptive AVF creations and slowing the progression of renal failure (17). Accordingly, the currently recommended approaches to permanent access placement based on a single threshold level of renal function for patients of all ages are not appropriate (8).

Prediction of CKD progression and timing of dialysis initiation

Based on observational data, most guidelines suggest that CKD patients should be referred to a nephrology service when the eGFR declines below 30 mL/min/1.73 m² (18, 19), although hard evidence to support such statement is still lacking. This threshold is also forwarded as the point where pre-dialysis work-up should start. Compliant CKD patients who have regular visits to the nephrologist over the time of CKD progression are expected to have optimally balanced volume status, anemia, phosphorus, and potassium control.

Several models have been developed to predict progression of CKD to ESRD. Echouffo-Tcheugui and Kengne (20) systematically reviewed the literature and identified 17 prediction models, many of them developed using inappropriate methods and generally poorly reported (21). One of the better performing models was developed by Tangri and co-workers (22). They developed a model to predict progression of CKD (stage 3-5) to ESRD based on data of more than 8000 referred patients using age, gender, estimated GFR, albuminuria and routinely collected laboratory data (serum calcium, serum phosphate, serum bicarbonate, serum albumin) (22). Tangri's kidney failure risk equation (KFRE) was validated by Peeters et al (23) who concluded that it is reliable for determining progression to ESRD in European CKD patients. In a recent meta-analysis on the accuracy of this risk equation across different geographic regions and patient populations based on individual patient record data, it proved to provide excellent discrimination to differentiate those who developed kidney failure from those who did not, across all cohorts (24). Accordingly, the KFRE was also adapted by European Renal Best Practice (ERBP) in its guideline on management of the elderly with advanced kidney disease to calculate the predicted timing of need for renal replacement therapy (25).

The Initiating Dialysis Early and Late (IDEAL) randomized controlled trial demonstrated there was no improvement in survival or clinical outcomes if patients were started based on eGFR <10 mL/min per 1.73 m² versus based on uremic symptoms (26). These data were confirmed in later studies (27, 28), especially in the elderly population (9). Accordingly, the IDEAL trial supported the current ERBP guideline (29), stating that RRT should not be started as long as patients are asymptomatic. Of note, in the IDEAL trial, the majority of patients had a functioning vascular access in place, and most patients had been under nephrology care for more than 6 months.

The IDEAL study also learns that in most patients with an eGFR between 10-15 mL/min/1.73 m², and who are deemed suitable for creation of an AVF, there is nearly always time to allow creation of such a fistula rather than starting dialysis in an emergency on a CVC. Indeed, the “late start” group started on average 6 months later on dialysis as compared to the “early start” group. From this, it can be derived that it is probably not very useful to start considering placement of vascular access before patients have reached an eGFR of 10-15 mL/min/1.7 3 m². As this land-mark can be predicted accurately using the KFRE, there is no real need to start creating an AVF before. The fixed time point suggested by some guidelines of “at least 6 months before the anticipated start of hemodialysis treatment” (19) to plan pre-emptive AFV creation can thus in fact not be maintained based on this recent evidence.

Such a strategy will also avoid unnecessary surgery in patients who will never start dialysis. Patients may not start dialysis either because their CKD will never progress to ESRD, or because they might die before needing dialysis due to a limited life expectancy (9, 28, 30). Attempting to pre-emptively place permanent access in these patients exposes them to a risk rather than a potential benefit.

Several studies (8, 31–32–33–34) analyzed median eGFR at the time of pre-emptive AVF placement, as well as the rate of initiating dialysis one year after pre-emptive vascular access surgery (Tab. I). These studies seem to confirm the proposed algorithm.

Table I

Studies analyzing the mean eGFR at the time of AVF creation and consequently, the rate of HD initiation during follow-up

Study	Mean eGFR at the time of AVF creation	Follow-up period	% of hemodialysis starts during follow-up
Bansal et al 2013 (31)	16.1 mL/min/1.73 m²	One year	61%
O'Hare et al 2007 (8)	17.7 mL/min/1.73 m²	One year	25%
Kimball et al 2011 (32)	>15 mL/min/1.73 m²	One year	49%
Weber et al 2009 (33)	12 mL/min/1.73 m²	Two years	70%
Oliver et al 2012 (34)	No data	Three years	81%

eGFR = estimated glomerular filtration rate; AVF = arteriovenous fistula; HD = hemodialysis.

Timing of first cannulation

There are significant differences among countries regarding practices of optimal duration of AVF maturation and timing of first cannulation, ranging from 1 to 6 months after construction (35–36–37–38). The last data from the DOPPS 5 study revealed that AVF puncture occurred within one month of construction in 94% Japanese HD centers, up to 38% in European, and in 27% in the USA (10).

Cannulating a newly created vascular access too early might result in perforation, hematoma or even destruction of the access site. On the other hand, waiting too long for a first cannulation attempt might expose the patient unnecessarily to the use of a catheter, and to delays in either investigating the causes of eventual non-maturation or the creation of an alternative permanent vascular access. In a large international multicenter cohort study, puncturing an autologous fistula earlier than two weeks after creation was associated with a 2-fold higher risk of fistula failure (39). The risk for failure decreased between week 2 and week 4, so, when possible, puncturing should be delayed until 4 weeks after creation.

However, in this period the benefit of a further delay to allow maturation should be balanced with potential drawbacks of such a delay. This is especially so if the alternative is to place a catheter to start dialysis in an emergency. In such conditions, an attempt to puncture the fistula to start dialysis should be done. This decision can be further underpinned based on presence of a palpable thrill, or ultrasound criteria. In patients who already started dialysis on a permanent catheter, it is recommendable to wait for 4 weeks after creation of the fistula, unless there is a problem with the catheter (40).

Fistulas older than 4 weeks with a palpable thrill can mostly be punctured successfully (41). In these conditions, no further ultrasound examination is needed, and cannulation can be attempted. However, when no palpable thrill is present, or cannulation is not successful, ultrasound should be performed for further evaluation. In line with clinical practice experience, vein diameter larger than 4-5 mm and/or a blood flow higher than 500 mL/min mostly indicate that the fistula has attained functional maturation and can be punctured successfully (37, 38, 42).

One study suggests using venous wall thickness to evaluate maturation of the fistula on top of blood flow and venous diameter (43). The technique and experience to measure venous wall thickness might not be universally available however, and further confirmation of this test is needed.

If the fistula has not matured (venous diameter <4-5 mm and/or blood flow <500 mL/min), further investigations for underlying reasons should be done to allow eventual interventions and salvage of the vascular access.

It should also be taken into account that additional barriers may be caused by differences between countries in the available surgical capacity, the availability of dedicated and trained clinicians, and the routine use or not of preoperative diagnostic imaging. All these factors might also affect the time needed to successfully create a functioning AVF before HD start (44).

Many factors have been associated with the probability of achieving a functioning AVF. A performant prognostic predictive model would be useful in guiding decisions on whether or not to attempt to create an AVF. A recent systematic review found four studies describing five prediction models for successful fistula maturation (45). Presence of cardiovascular disease and older age were the most important common factors in the prediction models, but other factors lacked communality between studies. A major weakness of the published models is the heterogeneity of the outcomes of interest, being AVF maturation, AVF non-maturation or AVF patency, which prohibits a meta-analysis of the data. None of the published models was externally validated, so it remains cumbersome to recommend their use in clinical practice.

What do guidelines state on this topic?

Caring for Australasians with Renal Impairment (CARI) states that all patients should be referred to a vascular access surgeon well in advance of the anticipated need for HD. The referral should be earlier in patients with comorbidities, such as vascular disease or diabetes (46). The exact timing also depends on local availability of vascular surgery services. The Canadian Society of Nephrology (CSN) recommends in their 2006 guidelines that vascular access creation should be considered at an eGFR of 15-20 mL/min per 1.73 m² (47), provided patients have proven progressive kidney disease. This allows an “intent-to-defer” strategy, whereby start of HD can be planned according to the presence of “emergent clinical indications” or when the eGFR is ≤6 mL/min per 1.73 m² (48). This attitude is in agreement with ERBP that eGFR should not be the factor of decisive importance for start RRT. UK Renal Association (UK-RA) recommends to plan vascular access already at the point where an individual reaches CKD stage 4 (49). According to UK-RA, the exact timing of placement of vascular access is determined by the rate of decline of renal function, co-morbidities and by the average duration the surgical pathway. In accordance with the guidance of the National Kidney Foundation/K-DOQI, patients should have a functional permanent access at the initiation of dialysis therapy. In order to achieve this goal, they recommend that fistula creation should be considered at least 6 months before the anticipated start of HD treatments (19). This timing allows for access evaluation and additional time for revision to ensure a working fistula is available at initiation of dialysis therapy.

Conclusion

It should be the intention to start chronic dialysis with a permanent vascular access in the majority of timely referred CKD patients, except in the comorbid and frail elderly patient. For estimation of the timing to start of dialysis, the Tangri KFRE should be used. The time for pre-emptive AVF placement should be determined according to patient characteristics and taking into account local logistical and organizational circumstances. Ideally, the AVF should be constructed at least 4 weeks before the initial cannulation. In most patients, creating an AVF only when they reach an eGFR <15 mL/min/1.73 m² would allow to achieve this goal, whilst avoiding spurious interventions in patients who will never need dialysis.

Footnotes

Acknowledgment

The authors are grateful to Sabine van der Veer for her help with drafting the original guideline chapter which was the starting point for this work.

Financial support: The data presented in the paper are the result of a systematic search performed in the framework of European Renal Best Practice (ERBP). European Renal Best Practice is supported by an unrestricted financial grant from European Renal Association/European Dialysis and Transplantation Association.

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

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